Valerie L. Baker, MD's Profile

All Publications

Midluteal Progesterone: A Marker of Treatment Outcomes in Couples With Unexplained Infertility JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Hansen, K. R., Eisenberg, E., Baker, V., Hill, M. J., Chen, S., Talken, S., Diamond, M. P., Legro, R. S., Coutifaris, C., Alvero, R., Robinson, R. D., Casson, P., Christman, G. M., Santoro, N., Zhang, H., Wild, R. A., NICHD Reproductive Med Network 2018; 103 (7): 2743–51

Abstract

Adequate luteal phase progesterone exposure is necessary to induce endometrial changes required for a successful pregnancy outcome. The relationship between low midluteal progesterone concentration and the outcome of live birth in ovarian stimulation with intrauterine insemination (OS-IUI) treatments is not defined.To determine the level of midluteal progesterone portending a low chance of live birth after OS-IUI in couples with unexplained infertility.Secondary analyses of data from a prospective, randomized, multicenter clinical trial that determined pregnancy outcomes following OS-IUI with clomiphene citrate, letrozole, or gonadotropins for couples with unexplained infertility.Couples (n = 900) underwent 2376 OS-IUI cycles during the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation clinical trial.Live birth as it relates to midluteal progesterone level and thresholds below which no live births occur by treatment group.Thresholds for non-live birth cycles were similar for clomiphene (14.4 ng/mL) and letrozole (13.1 ng/mL) yet were lower for gonadotropin (4.3 ng/mL) treatments. A midluteal progesterone level >10th percentile specific for each treatment group independently was associated with greater odds for a live birth in all OS-IUI cycles (adjusted OR: 2.17; 95% CI: 1.05, 4.48).During OS-IUI, a low midluteal progesterone level was associated with a low probability of live birth. Thresholds differed by medication, with the lowest threshold for gonadotropin. Several pathophysiologic mechanisms may account for low progesterone levels. Refinement of the predictive range associated with particular ovarian stimulation medications during treatment of unexplained infertility may improve accuracy.

View details for DOI 10.1210/jc.2018-00642

View details for Web of Science ID 000438162300035

View details for PubMedID 29767754
Multicenter evaluation of the Access AMH antimullerian hormone assay for the prediction of antral follicle count and poor ovarian response to controlled ovarian stimulation. Fertility and sterility Baker, V. L., Gracia, C., Glassner, M. J., Schnell, V. L., Doody, K., Coddington, C. C., Shin, S. S., Marshall, L. A., Alper, M. M., Morales, A. J., Pavone, M. E., Behera, M. A., Zbella, E. A., Shapiro, B. S., Straseski, J. A., Broyles, D. L. 2018

Abstract

OBJECTIVE: To evaluate a new fully automated antimullerian hormone (AMH) assay for prediction of poor ovarian response (POR) to ovarian stimulation defined as four or fewer oocytes retrieved.DESIGN: Prospective cohort study.SETTING: Thirteen private and academic fertility centers in the United States.PATIENTS(S): A total of 178 women undergoing their first invitro fertilization (IVF) cycle eligible for the study were consented and enrolled, with data available from 160 women for prediction of POR and 164 women for AMH correlation with antral follicle count (AFC).INTERVENTION(S): None.MAIN OUTCOME MEASURE(S): Cutoff point for AMH that predicts POR. Correlation of AMH with AFC, and cutoff point for AMH that correlates with antral follicle count >15.RESULT(S): The mean AMH among the poor responders was 0.74ng/mL, compared with 3.20ng/mL for normal to high responders. The AMH cutoff at 90% specificity for predicting POR with the use of the receiver operating characteristic (ROC) curve was 0.93ng/mL, with an associated sensitivity of 74.1%. For prediction of POR, ROC analysis showed that AMH (area under the ROC curve [AUC] = 0.929) was significantly better than FSH (AUC = 0.615; P<.0001). AMH was positively correlated with AFC (Spearman rho = 0.756). The AMH at 90% sensitivity for AFC >15 was 1.75, with specificity of 59.1%.CONCLUSION(S): A fully automated AMH assay can be a useful biomarker for predicting POR in IVF cycles. Because AMH cutoff points vary depending on the assay used, future studies should continue to calibrate test results to clinically important outcomes.

View details for DOI 10.1016/j.fertnstert.2018.03.031

View details for PubMedID 29960708
Use of human-derived stem cells to create a novel, in vitro model designed to explore FMR1 CGG repeat instability amongst female premutation carriers. Journal of assisted reproduction and genetics Gustin, S. L., Wang, G., Baker, V. M., Latham, G., Sebastiano, V. 2018

Abstract

OBJECTIVE: Create a model, using reprogrammed cells, to provide a platform to identify the mechanisms of CGG repeat instability amongst female fragile X mental retardation 1 gene (FMR1) premutation (PM) carriers.METHODS: Female PM carriers (with and without POI) and healthy controls were enrolled from June 2013 to April 2014. Patient-derived fibroblasts (FB) were reprogrammed to induced pluripotent stem cells (iPSC) using viral vectors, encoding KLF4, OCT4, SOX2, and MYC. FMR1 CGG repeat-primed PCR was used to assess the triplet repeat structure of the FMR1 gene. FMR1 promoter methylation (%) was determined using FMR1 methylation PCR (mPCR). Quantification of FMR1 transcripts by RT-qPCR was used to evaluate the effect of reprogramming on gene transcription, as well as to correlate patient phenotype with FMR1 expression. Production of FMR1 protein (FMRP) was determined using a liquid bead array-based immunoassay.RESULTS: Upon induction to pluripotency, all control clones exhibited maintenance of progenitor cell CGG repeat number, whereas 10 of 12 clones derived from PM carriers maintained their input CGG repeat number, one of which expanded and one contracted. As compared to parent FB, iPSC clones exhibited a skewed methylation pattern; however, downstream transcription and translation appeared unaffected. Further, the PM carriers, regardless of phenotype, exhibited similar FMR1 transcription and translation to the controls.CONCLUSIONS: This is the first study to establish a stem cell model aimed to understand FMR1 CGG repeat instability amongst female PM carriers. Our preliminary data indicate that CGG repeat number, transcription, and translation are conserved upon induction to pluripotency.

View details for DOI 10.1007/s10815-018-1237-y

View details for PubMedID 29926373
First trimester pregnancy ultrasound findings as a function of method of conception in an infertile population. Journal of assisted reproduction and genetics von Versen-Hoynck, F., Petersen, J. S., Chi, Y., Liu, J., Baker, V. L. 2018; 35 (5): 863–70

Abstract

PURPOSE: The aim of this study was to determine whether first trimester ultrasound measurements of crown rump length (CRL) and gestational sac diameter (GSD) differ depending on the method of conception among infertile women.METHOD: Infertile women, ages 21-50years old, who conceived viable, singleton pregnancies via fresh embryo transfer (ET), frozen ET, non-in vitro fertilization (IVF) fertility treatment, or spontaneously were included in this observational cohort study at an academic fertility practice. Embryonic growth trajectories defined by the CRL and GSD at 6 and 8 weeks' gestation were analyzed and compared among the methods of conception.RESULTS: Crown rump length at 6weeks' gestation was smaller for conceptions achieved via fresh ET compared with frozen ET in a natural cycle (1.50 vs. 2.50mm, p=0.017). Crown rump length was smaller at 8weeks' gestation in conceptions achieved via fresh ET compared to frozen ET in a programmed cycle (16.13 vs. 17.02mm, p=0.039).CONCLUSION: Among infertile women, embryo growth may differ between fresh and frozen ET as early as 6 and 8weeks' gestation.

View details for DOI 10.1007/s10815-018-1120-x

View details for PubMedID 29380277
Decreased Maternal Circulating Progenitor Cells-A Connection to Corpus Lutea Number. von Versen-Hoynck, F., Narasimhan, P., Martinez, N., Baker, V. L., Winn, V. D. SAGE PUBLICATIONS INC. 2018: 313A

View details for Web of Science ID 000429928200783
Prediction of Antral Follicle Count with the Automated Elecsys (R) Anti-Mullerian Hormone (AMH) Immunoassay in a Multi-Center Prospective Study Jacobs, M. H., Reuter, L., Baker, V., Craig, L. B., Sakkas, D., Surrey, E., Doody, K., Jungheim, E., Bayrak, A. B., Hund, M., Verhagen-Kamerbeek, W., Pardue, D., Buck, K., Timm, B. SAGE PUBLICATIONS INC. 2018: 252A

View details for Web of Science ID 000429928200593
Antimullerian hormone as a predictor of live birth following assisted reproduction: an analysis of 85,062 fresh and thawed cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for 2012-2013 FERTILITY AND STERILITY Tal, R., Seifer, D. B., Wantman, E., Baker, V., Tal, O. 2018; 109 (2): 258–65

Abstract

To determine if serum antimüllerian hormone (AMH) is associated with and/or predictive of live birth assisted reproductive technology (ART) outcomes.Retrospective analysis of Society for Assisted Reproductive Technology Clinic Outcome Reporting System database from 2012 to 2013.Not applicable.A total of 69,336 (81.8%) fresh and 15,458 (18.2%) frozen embryo transfer (FET) cycles with AMH values.None.Live birth.A total of 85,062 out of 259,499 (32.7%) fresh and frozen-thawed autologous non-preimplantation genetic diagnosis cycles had AMH reported for cycles over this 2-year period. Of those, 70,565 cycles which had embryo transfers were included in the analysis. Serum AMH was significantly associated with live birth outcome per transfer in both fresh and FET cycles. Multiple logistic regression demonstrated that AMH is an independent predictor of live birth in fresh transfer cycles and FET cycles when controlling for age, body mass index, race, day of transfer, and number of embryos transferred. Receiver operating characteristic (ROC) curves demonstrated that the areas under the curve (AUC) for AMH as predictors of live birth in fresh cycles and thawed cycles were 0.631 and 0.540, respectively, suggesting that AMH alone is a weak independent predictor of live birth after ART. Similar ROC curves were obtained also when elective single-embryo transfer (eSET) cycles were analyzed separately in either fresh (AUC 0.655) or FET (AUC 0.533) cycles, although AMH was not found to be an independent predictor in eSET cycles.AMH is a poor independent predictor of live birth outcome in either fresh or frozen embryo transfer for both eSET and non-SET transfers.

View details for DOI 10.1016/j.fertnstert.2017.10.021

View details for Web of Science ID 000424939300020

View details for PubMedID 29331235
Effect of Mode of Conception on Maternal Serum Relaxin, Creatinine, and Sodium Concentrations in an Infertile Population. Reproductive sciences (Thousand Oaks, Calif.) von Versen-Hoynck, F., Strauch, N. K., Liu, J., Chi, Y., Keller-Woods, M., Conrad, K. P., Baker, V. L. 2018: 1933719118776792

Abstract

OBJECTIVE: To investigate how the mode of conception affects maternal relaxin, creatinine, and electrolyte concentrations.BACKGROUND: Pregnancies achieved by fertility treatment often begin in a nonphysiologic endocrine milieu with no corpus luteum (CL) or with many corpora lutea. The CL produces not only estradiol and progesterone but is also the sole source of relaxin in early pregnancy, a hormone that may contribute to maternal systemic and renal vasodilation. There is limited data about maternal physiology in early pregnancy during fertility treatment, and studies have rarely considered the potential effect of the absence of the CL. To begin to address this gap in knowledge, we sought to investigate how the mode of conception affects maternal relaxin, creatinine, and electrolyte concentrations.METHODS: One hundred eighty-four women who received care at an academic infertility practice provided serum samples. Levels of relaxin 2, creatinine, and electrolytes were compared between 4 groups defined on the basis of mode of conception which corresponded to categories of CL number: (1) absence of the CL, (2) single CL, (3) multiple CL from ovarian stimulation not including in vitro fertilization (IVF), and (4) multiple CL from IVF with fresh embryo transfer.RESULTS: Relaxin-2 levels were undetectable in patients lacking a CL. Creatinine, sodium, and total CO2 levels were significantly higher in the 0 CL group (relaxin absent) compared to all other groups (relaxin present). Compared to clomiphene, use of letrozole was associated with a lower relaxin level.CONCLUSION: Early creatinine and sodium concentrations are increased in the absence of relaxin. Given the increasing utilization of frozen embryo transfer, further studies comparing programmed with natural cycles are warranted.

View details for DOI 10.1177/1933719118776792

View details for PubMedID 29862889
Sexual function in infertile women with polycystic ovary syndrome and unexplained infertility. American journal of obstetrics and gynecology Diamond, M. P., Legro, R. S., Coutifaris, C., Alvero, R., Robinson, R. D., Casson, P. A., Christman, G. M., Huang, H., Hansen, K. R., Baker, V., Usadi, R., Seungdamrong, A., Bates, G. W., Rosen, R. M., Schlaff, W., Haisenleder, D., Krawetz, S. A., Barnhart, K., Trussell, J. C., Santoro, N., Eisenberg, E., Zhang, H. 2017

Abstract

While female sexual dysfunction is a frequent occurrence, characteristics in infertile women are not well delineated. Furthermore, the impact of infertility etiology on the characteristics in women with differing androgen levels observed in women with polycystic ovary syndrome and unexplained infertility has not been assessed.The objective of the study was to determine the characteristics of sexual dysfunction in women with polycystic ovary syndrome and unexplained infertility.A secondary data analysis was performed on 2 of Eunice Kennedy Shriver National Institute of Child Health and Human Development Cooperative Reproductive Medicine Networks clinical trials: Pregnancy in Polycystic Ovary Syndrome Study II and Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation. Both protocols assessed female sexual function using the Female Sexual Function Inventory and the Female Sexual Distress Scale.Women with polycystic ovary syndrome had higher weight and body mass index than women with unexplained infertility (each P < .001), greater phenotypic (Ferriman-Gallwey hirsutism score, sebum score, and acne score; each P < .001), and hormonal (testosterone, free testosterone, and dehydroepiandrosterone; each P < .001) evidence of androgen excess. Sexual function scores, as assessed by the Female Sexual Function Inventory, were nearly identical. The Female Sexual Distress Scale total score was higher in women with polycystic ovary syndrome. The mean Female Sexual Function Inventory total score increased slightly as the free androgen index increased, mainly as a result of the desire subscore. This association was more pronounced in the women with unexplained infertility.Reproductive-age women with infertility associated with polycystic ovary syndrome and unexplained infertility, despite phenotypic and biochemical differences in androgenic manifestations, do not manifest clinically significant differences in sexual function.

View details for DOI 10.1016/j.ajog.2017.04.034

View details for PubMedID 28455078
Warm reception for frozen embryos, but should a hot trend still be kept on ice? FERTILITY AND STERILITY Kort, J. D., Lathi, R. B., Baker, V. 2017; 107 (3): 575-576

View details for DOI 10.1016/j.fertnstert.2017.01.004

View details for Web of Science ID 000397985500012

View details for PubMedID 28189297
Distribution of the FMR1 gene in females by race/ethnicity: women with diminished ovarian reserve versus women with normal fertility (SWAN study) FERTILITY AND STERILITY Pastore, L. M., Young, S. L., Manichaikul, A., Baker, V. L., Wang, X. Q., Finkelstein, J. S. 2017; 107 (1): 205-?

Abstract

To study whether reported, but inconsistent, associations between the FMR1 CGG repeat lengths in the intermediate, high normal, or low normal range differentiate women diagnosed with diminished ovarian reserve (DOR) from population controls and whether associations vary by race/ethnic group.Case-control study.Academic and private fertility clinics.DOR cases (n = 129; 95 Whites, 22 Asian, 12 other) from five U.S. fertility clinics were clinically diagnosed, with regular menses and no fragile X syndrome family history. Normal fertility controls (n = 803; 386 Whites, 219 African-Americans, 102 Japanese, 96 Chinese) from the United States-based SWAN Study had one or more menstrual period in the 3 months pre-enrollment, one or more pregnancy, no history of infertility or hormone therapy, and menopause ≥46 years. Previously, the SWAN Chinese and Japanese groups had similar FMR1 CGG repeat lengths, thus they were combined.None.FMR1 CGG repeat lengths.Median CGG repeats were nearly identical by case/control group. DOR cases had fewer CGG repeats in the shorter FMR1 allele than controls among Whites, but this was not significant among Asians. White cases had fewer CGG repeats in the shorter allele than Asian cases. No significant differences were found in the high normal/intermediate range between cases and controls or by race/ethnic group within cases in the longer allele.This study refutes prior reports of an association between DOR and high normal/intermediate repeats and confirms an association between DOR and low normal repeats in Whites.

View details for DOI 10.1016/j.fertnstert.2016.09.032

View details for Web of Science ID 000390669600036
Distribution of the FMR1 gene in females by race/ethnicity: women with diminished ovarian reserve versus women with normal fertility (SWAN study). Fertility and sterility Pastore, L. M., Young, S. L., Manichaikul, A., Baker, V. L., Wang, X. Q., Finkelstein, J. S. 2016

Abstract

To study whether reported, but inconsistent, associations between the FMR1 CGG repeat lengths in the intermediate, high normal, or low normal range differentiate women diagnosed with diminished ovarian reserve (DOR) from population controls and whether associations vary by race/ethnic group.Case-control study.Academic and private fertility clinics.DOR cases (n = 129; 95 Whites, 22 Asian, 12 other) from five U.S. fertility clinics were clinically diagnosed, with regular menses and no fragile X syndrome family history. Normal fertility controls (n = 803; 386 Whites, 219 African-Americans, 102 Japanese, 96 Chinese) from the United States-based SWAN Study had one or more menstrual period in the 3 months pre-enrollment, one or more pregnancy, no history of infertility or hormone therapy, and menopause ≥46 years. Previously, the SWAN Chinese and Japanese groups had similar FMR1 CGG repeat lengths, thus they were combined.None.FMR1 CGG repeat lengths.Median CGG repeats were nearly identical by case/control group. DOR cases had fewer CGG repeats in the shorter FMR1 allele than controls among Whites, but this was not significant among Asians. White cases had fewer CGG repeats in the shorter allele than Asian cases. No significant differences were found in the high normal/intermediate range between cases and controls or by race/ethnic group within cases in the longer allele.This study refutes prior reports of an association between DOR and high normal/intermediate repeats and confirms an association between DOR and low normal repeats in Whites.

View details for DOI 10.1016/j.fertnstert.2016.09.032

View details for PubMedID 27816231
Relationship between paternal somatic health and assisted reproductive technology outcomes. Fertility and sterility Eisenberg, M. L., Li, S., Wise, L. A., Lynch, C. D., Nakajima, S., Meyers, S. A., Behr, B., Baker, V. L. 2016; 106 (3): 559-565

Abstract

To study the association between paternal medical comorbidities and the outcomes of assisted reproductive technology (ART).Retrospective cohort study.Academic reproductive medicine center.We analyzed fresh ART cycles uszing freshly ejaculated sperm from the male partner of couples undergoing ART cycles from 2004 until 2014. We recorded patient and partner demographic characteristics. The cohort was linked to hospital billing data to obtain information on selected male partners' comorbidities identified using ICD-9-CM codes.None.Fertilization, clinical pregnancy, miscarriage, implantation, and live-birth rates as well as birth weights and gestational ages.In all, we identified 2,690 men who underwent 5,037 fresh ART cycles. Twenty-seven percent of men had at least one medical diagnosis. Men with nervous system diseases had on average lower pregnancy rates (23% vs. 30%) and live-birth rates (15% vs. 23%) than men without nervous system diseases. Lower fertilization rates were also observed among men with respiratory diseases (61% vs. 64%) and musculoskeletal diseases (61% vs. 64%) relative to those without these diseases. In addition, men with diseases of the endocrine system had smaller children (2,970 vs. 3,210 g) than men without such diseases. Finally, men with mental disorders had children born at an earlier gestational age (36.5 vs. 38.0 weeks).The current report identified a possible relationship between a man's health history and IVF outcomes. As these are potentially modifiable factors, further research should determine whether treatment for men's health conditions may improve or impair IVF outcomes.

View details for DOI 10.1016/j.fertnstert.2016.04.037

View details for PubMedID 27179785
Collection of pregnancy outcome records following infertility-challenges and possible solutions. Journal of assisted reproduction and genetics Floyd, E. G., von Versen-Höynck, F., Liu, J., Chi, Y., Fleischmann, R. R., Baker, V. L. 2016; 33 (8): 993-999

Abstract

The aim of this study is to report challenges encountered when conducting inter-institutional data collection of obstetric (prenatal and postpartum) and delivery outcomes for research purposes and to propose solutions for enhanced efficiency.Data were collected from women who consented to collection of obstetric and delivery records for an observational study of pregnancy and delivery outcomes following infertility treatment. We analyzed key issues relevant to improving efficiency of obstetric and delivery data collection via quantification of effort (such as number of calls and faxes) required to obtain records from different types of obstetric clinics and hospitals before and after utilization of a revised authorization.At time of analysis, records were successfully collected from 320 of the 451 participants who had delivered. The 320 participants received obstetric care at 63 institutions and delivered at 27 hospitals, with 168 (52.5 %) delivering at institutions other than home facility. At time of consent (8 weeks gestation), 155 of 320 (48.5 %) correctly predicted where they would receive obstetric care and 176 (55 %) where they would delivery. Most facilities (nearly 90 %) rejected our original authorization, but most (90 %) accepted the revised authorization described in this manuscript.Collecting records is time-consuming but important as over 50 % of our participants received care outside of the home facility. To efficiently collect outside records, we recommend that researchers interested in maternal and neonatal outcomes consider the guidelines outlined in this manuscript. This report also provides strong evidence of the need to develop data sharing through electronic health records for research purposes.

View details for DOI 10.1007/s10815-016-0733-1

View details for PubMedID 27230878
Benefit of Delayed Fertility Therapy With Preconception Weight Loss Over Immediate Therapy in Obese Women With PCOS JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Legro, R. S., Dodson, W. C., Kunselman, A. R., Stetter, C. M., Kris-Etherton, P. M., Williams, N. I., Gnatuk, C. L., Estes, S. J., Allison, K. C., Sarwer, D. B., Diamond, M. P., Schlaff, W. D., Casson, P. R., Christman, G. M., Barnhart, K. T., Bates, G. W., Usadi, R., Lucidi, S., Baker, V., Zhang, H., Eisenberg, E., Coutifaris, C., Dokras, A. 2016; 101 (7): 2658-2666

Abstract

In overweight/obese women with polycystic ovary syndrome (PCOS), the relative benefit of delaying infertility treatment to lose weight vs seeking immediate treatment is unknown.We compared the results of two, multicenter, concurrent clinical trials treating infertility in women with PCOS.This was a secondary analysis of two randomized trials conducted at academic health centers studying women 18-40 years of age who were overweight/obese and infertile with PCOS.We compared immediate treatment with clomiphene from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial (N = 187) to delayed treatment with clomiphene after preconception treatment with continuous oral contraceptives, lifestyle modification (Lifestyle: including caloric restriction, antiobesity medication, behavioral modification, and exercise) or the combination of both (combined) from the Treatment of Hyperandrogenism Versus Insulin Resistance in Infertile Polycystic Ovary Syndrome (OWL PCOS) trial (N = 142).Live birth, pregnancy loss, and ovulation were measured.In PPCOS II, after four cycles of clomiphene, the cumulative per-cycle ovulation rate was 44.7% (277/619) and the cumulative live birth rate was 10.2% (19/187), nearly identical to that after oral contraceptive pretreatment in the OWL PCOS trial (ovulation 45% [67/149] and live birth: 8.5% [4/47]). In comparison, deferred clomiphene treatment preceded by lifestyle and combined treatment in OWL PCOS offered a significantly better cumulative ovulation rate compared to immediate treatment with clomiphene. (Lifestyle: 62.0% [80/129]; risk ratio compared to PPCOS II = 1.4; 95% confidence interval [CI], 1.1-1.7; P = .003; combined: 64.3% [83/129]; risk ratio compared to PPCOS II = 1.4; 95% CI, 1.2-1.8; P < .001 and a significantly better live birth rate lifestyle: 25.0% [12/48]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.7; P = .01 and combined: 25.5% [12/47]; risk ratio compared to PPCOS II = 2.5; 95% CI, 1.3-4.8; P = .01).These data show the benefit of improved ovulation and live birth with delayed infertility treatment with clomiphene citrate when preceded by lifestyle modification with weight loss compared with immediate treatment. Pretreatment with oral contraceptives likely has little effect on the ovulation and live birth rate compared with immediate treatment.

View details for DOI 10.1210/jc.2016-1659

View details for Web of Science ID 000380224800007

View details for PubMedID 27172435
Factors associated with the use of elective single-embryo transfer and pregnancy outcomes in the United States, 2004-2012 FERTILITY AND STERILITY Styer, A. K., Luke, B., Vitek, W., Christianson, M. S., Baker, V. L., Christy, A. Y., Polotsky, A. J. 2016; 106 (1): 80-89

Abstract

To evaluate factors associated with elective single-embryo transfer (eSET) utilization and its effect on assisted reproductive technology outcomes in the United States.Historical cohort.Not applicable.Fresh IVF cycles of women aged 18-37 years using autologous oocytes with either one (SET) or two (double-embryo transfer [DET]) embryos transferred and reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System between 2004 and 2012. Cycles were categorized into four groups with ([+]) or without ([-]) supernumerary embryos cryopreserved. The SET group with embryos cryopreserved was designated as eSET.None.The likelihood of eSET utilization, live birth, and singleton non-low birth weight term live birth, modeled using logistic regression. Presented as adjusted odds ratios (aORs) and 95% confidence intervals (CIs).The study included 263,375 cycles (21,917 SET[-]cryopreservation, 20,996 SET[+]cryopreservation, 103,371 DET[-]cryopreservation, and 117,091 DET[+]cryopreservation). The utilization of eSET (SET[+]cryopreservation) increased from 1.8% in 2004 to 14.9% in 2012 (aOR 7.66, 95% CI 6.87-8.53) and was more likely with assisted reproductive technology insurance coverage (aOR 1.60, 95% CI 1.54-1.66), Asian race (aOR 1.26, 95% CI 1.20-1.33), uterine factor diagnosis (aOR 1.48, 95% CI 1.37-1.59), retrieval of ≥16 oocytes (aOR 2.85, 95% CI 2.55-3.19), and the transfer of day 5-6 embryos (aOR 4.23, 95% CI 4.06-4.40); eSET was less likely in women aged 35-37 years (aOR 0.76, 95% CI 0.73-0.80). Compared with DET cycles, the likelihood of the ideal outcome, term non-low birth weight singleton live birth, was increased 45%-52% with eSET.Expanding insurance coverage for IVF would facilitate the broader use of eSET and may reduce the morbidity and healthcare costs associated with multiple pregnancies.

View details for DOI 10.1016/j.fertnstert.2016.02.034

View details for Web of Science ID 000380071800016

View details for PubMedID 26997248
In vitro fertilization outcomes after fresh and frozen blastocyst transfer in South Asian compared with Caucasian women FERTILITY AND STERILITY Shah, M. S., Caballes, M., Lathi, R. B., Baker, V. L., Westphal, L. M., Milki, A. A. 2016; 105 (6): 1484-1487

Abstract

To study pregnancy outcomes between South Asian and Caucasian women undergoing frozen blastocyst transfer cycles.Retrospective cohort study.Not applicable.Caucasian and South Asian patients undergoing frozen blastocyst transfer between January 2011 and December 2014.Not applicable.Live birth rate.A total of 196 Caucasian and 117 South Asian women were included in our study. Indians were on average 2.2 years younger than Caucasian women (34.9 vs. 37.1 years), and were more likely to be nulliparous (59% vs. 43%). All other baseline characteristics were similar. In women undergoing their first frozen ET cycle, implantation rate (49% vs. 47%), clinical pregnancy rate (PR; 54% vs. 49%), and live birth rate (43% vs. 43%) were similar between South Asians and Caucasians, respectively. In patients who underwent a prior fresh blastocyst transfer, the live birth rate was significantly lower in South Asian versus Caucasian women (21% vs. 37%).Our data demonstrate that IVF outcomes are better in frozen versus fresh cycles among South Asian women. The IVF clinics may wish to consider these findings when counseling South Asian patients about the timing of ET.

View details for DOI 10.1016/j.fertnstert.2016.02.027

View details for Web of Science ID 000377290900019

View details for PubMedID 26952781
Practice patterns, satisfaction, and demographics of reproductive endocrinologists: results of the 2014 Society for Reproductive Endocrinology and Infertility Workforce Survey FERTILITY AND STERILITY Barnhart, K. T., Nakajima, S. T., Puscheck, E., Price, T. M., Baker, V. L., Segars, J. 2016; 105 (5): 1281-1286

Abstract

To identify the current and future state of the practice of reproductive medicine.Cross-sectional survey.Not applicable.None.Not applicable.The survey included 57 questions designed to assess practice patterns/metrics and professional satisfaction and morale.A total of 336/1,100 (31%) responded, and they were 38% women, 61% men, and 76% Caucasian, with a mean age of 54. Respondents averaged 2.3 jobs and averaged 53 hours of work per week: 44% work in academia and 50% in private groups. Average practice size was 5.5, with an average of 470 fresh IVF cycles performed per year. Percent effort included 63% infertility, 10% endocrinology, 10% surgery, and 9% research. Respondents performed an average of 13 major surgeries, 69 minor surgeries, and 128 oocyte retrievals per year. A total of 60% were salaried, and 40% were equity partners. Compensation was highly skewed. Greater than 84% had a positive morale and had a positive view of the future, and 92% would again choose REI as a career. The most satisfying areas of employment were patient interactions, intellectual stimulation, interactions with colleagues, and work schedule. The least satisfying areas were work schedule and financial compensation. Training was felt to be too focused on female factor infertility and basic research with insufficient training on embryology, genetics, male factor infertility, and clinical research. In the next 5 years, 57% suggested that the need for specialists would stay the same, while 20% predicted a decrease. A total of 58% felt we are training the correct number of fellows (37% felt we are training a surplus). Compared with academia, those in private practice reported higher compensation, less major surgery, more IVF, less endocrinology, and less research. Men worked more hours, conducted more surgery and IVF cycles, and had higher compensation than women. Morale was similar across age, gender, practice type, and geography.Our subspecialty has an extremely high morale. We are a middle-aged subspecialty with disparate compensation and a focused practice. Some respondents sense a need for a change in our training, and most anticipate only mild growth in our field.

View details for DOI 10.1016/j.fertnstert.2015.12.135

View details for Web of Science ID 000375871200036

View details for PubMedID 26774576
Prognostic indicators of assisted reproduction technology outcomes of cycles with ultralow serum antimullerian hormone: a multivariate analysis of over 5,000 autologous cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System database for 2012-2013 FERTILITY AND STERILITY Seifer, D. B., Tal, O., Wantman, E., Edul, P., Baker, V. L. 2016; 105 (2): 385-?

Abstract

To assess cycle outcomes when antimüllerian hormone (AMH) is ultralow (≤0.16 ng/mL) and to determine which parameters contribute to the probability of cycle cancellation and/or outcome.Retrospective analysis.Not applicable.5,087 (7.3%) fresh and 243 (1.5%) thawed cycles with ultralow AMH values.Linear and logistic regression, comparison with age-matched cycles with normal AMH concentrations.Cancellation rate; number of retrieved oocytes, embryos, transferred embryos, and cryopreserved embryos; clinical pregnancy, live-birth, and multiple birth rates.The total cancellation rate per cycle start for fresh cycles was 54%. Of these, 38.6% of the cycles were canceled before retrieval, and 3.3% of cycles obtained no oocytes at time of retrieval. Of all retrieval attempts, 50.7% had three oocytes or fewer retrieved, and 25.1% had no embryo transfer. The live-birth rates were 9.5% per cycle start. Cycles with ultralow AMH levels compared with age-matched normal AMH cycles demonstrated more than a fivefold greater pre-retrieval cancellation rate, a twofold less live-birth rate per cycle and a 4.5-fold less embryo cryopreservation rate.Refusing treatment solely on the basis of ultralow AMH levels is not advisable, but patients should be counseled appropriately about the prognostic factors for cancellation and outcomes.

View details for DOI 10.1016/j.fertnstert.2015.10.004

View details for Web of Science ID 000373405900026

View details for PubMedID 26515380
Recruitment strategies in two reproductive medicine network infertility trials CONTEMPORARY CLINICAL TRIALS Usadi, R. S., Diamond, M. P., Legro, R. S., Schlaff, W. D., Hansen, K. R., Casson, P., Christman, G., Bates, G. W., Baker, V., Seungdamrong, A., Rosen, M. P., Lucidi, S., Thomas, T., Huang, H., Santoro, N., Eisenberg, E., Zhang, H., Alvero, R. 2015; 45: 196-200

View details for DOI 10.1016/j.cct.2015.09.010

View details for Web of Science ID 000367755200009
Gonadotropin dose is negatively correlated with live birth rate: analysis of more than 650,000 assisted reproductive technology cycles FERTILITY AND STERILITY Baker, V. L., Brown, M. B., Luke, B., Smith, G. W., Ireland, J. J. 2015; 104 (5): 1145-?

View details for DOI 10.1016/j.fertnstert.2015.07.1151

View details for Web of Science ID 000366486400019

View details for PubMedID 26297646
Evidence of an age-related correlation of ovarian reserve and FMR1 repeat number among women with "normal" CGG repeat status JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Gustin, S. L., Ding, V. Y., Desai, M., Leader, B., Baker, V. L. 2015; 32 (11): 1669-1676

View details for DOI 10.1007/s10815-015-0577-0

View details for Web of Science ID 000365282800013

View details for PubMedID 26409477
Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility NEW ENGLAND JOURNAL OF MEDICINE Diamond, M. P., Legro, R. S., Coutifaris, C., Alvero, R., Robinson, R. D., Casson, P., Christman, G. M., Ager, J., Huang, H., Hansen, K. R., Baker, V., Usadi, R., Seungdamrong, A., Bates, G. W., Rosen, R. M., HAISENLEDER, D., Krawetz, S. A., Barnhart, K., Trussell, J. C., Ohl, D., Jin, Y., Santoro, N., Eisenberg, E., Zhang, H. 2015; 373 (13): 1230-1240

Abstract

The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates.We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies.After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P=0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P=0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P=0.15) or clomiphene alone (8 of 85, 9%; P=0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P=0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications.In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.).

View details for DOI 10.1056/NEJMoa1414827

View details for Web of Science ID 000361635200008

View details for PubMedID 26398071

View details for PubMedCentralID PMC4739644
Identification and replication of prediction models for ovulation, pregnancy and live birth in infertile women with polycystic ovary syndrome. Human reproduction Kuang, H., Jin, S., Hansen, K. R., Diamond, M. P., Coutifaris, C., Casson, P., Christman, G., Alvero, R., Huang, H., Bates, G. W., Usadi, R., Lucidi, S., Baker, V., Santoro, N., Eisenberg, E., Legro, R. S., Zhang, H. 2015; 30 (9): 2222-2233

Abstract

Can we build and validate predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS)?We were able to develop and validate a predictive model for pregnancy outcomes in women with PCOS using simple clinical and biochemical criteria particularly duration of attempting conception, which was the most consistent predictor among all considered factors for pregnancy outcomes.Predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome have been reported, but such models require validation.This is a secondary analysis of the data from the Pregnancy in Polycystic Ovary Syndrome I and II (PPCOS-I and -II) trials. Both trials were double-blind, randomized clinical trials that included 626 and 750 infertile women with PCOS, respectively. PPCOS-I participants were randomized to either clomiphene citrate (CC), metformin, or their combination, and PPCOS-II participants to either letrozole or CC for up to five treatment cycles.Linear logistic regression models were fitted using treatment, BMI, and other published variables as predictors of ovulation, conception, clinical pregnancy, and live birth as the outcome one at a time. We first evaluated previously reported significant predictors, and then constructed new prediction models. Receiver operating characteristic (ROC) curves were constructed and the area under the curves (AUCs) was calculated to compare performance using different models and data. Chi-square tests were used to examine the goodness-of-fit and prediction power of logistic regression model.Predictive factors were similar between PPCOS-I and II, but the two participant samples differed statistically significantly but the differences were clinically minor on key baseline characteristics and hormone levels. Women in PPCOS-II had an overall more severe PCOS phenotype than women in PPCOS-I. The clinically minor but statistically significant differences may be due to the large sample sizes. Younger age, lower baseline free androgen index and insulin, shorter duration of attempting conception, and higher baseline sex hormone-binding globulin significantly predicted at least one pregnancy outcome. The ROC curves (with AUCs of 0.66-0.76) and calibration plots and chi-square tests indicated stable predictive power of the identified variables (P-values ≥0.07 for all goodness-of-fit and validation tests).This is a secondary analysis. Although our primary objective was to confirm previously reported results and identify new predictors of ovulation and pregnancy outcomes among PPCOS-II participants, our approach is exploratory and warrants further replication.We have largely confirmed the predictors that were identified in the PPCOS-I trial. However, we have also revealed new predictors, particularly the role of smoking. While a history of ever smoking was not a significant predictor for live birth, a closer look at current, quit, and never smoking revealed that current smoking was a significant risk factor.The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Grants U10 HD27049, U10 HD38992, U10HD055925, U10 HD39005, U10 HD33172, U10 HD38998, U10 HD055936, U10 HD055942, and U10 HD055944; and U54-HD29834. Heilongjiang University of Chinese Medicine Grants 051277 and B201005. R.S.L. reports receiving consulting fees from Euroscreen, AstraZeneca, Clarus Therapeutics, and Takeda, and grant support from Ferring, Astra Zeneca, and Toba. K.R.H. reports receiving grant support from Roche Diagnostics and Ferring Pharmascience. G.C. reports receiving Honorarium and grant support from Abbvie Pharmaceuticals and Bayer Pharmaceuticals. M.P.D. holds equity from Advanced Reproductive Care Inc. and DS Biotech, receives fees from Advanced Reproductive Care Inc., Actamax, Auxogyn, ZSX Medical, Halt Medical, and Neomed, and receives grant support from Boehringer-Ingelheim, Abbott, and BioSante, Ferring Pharmaceuticals, and EMD Serono. H.Z. receives research support from the Chinese 1000-scholar plan. Others report no disclosures other than NIH grant support.PPCOS-I and -II were respectively registered at Clinicaltrials.gov: NCT00719186 and NCT00719186.

View details for DOI 10.1093/humrep/dev182

View details for PubMedID 26202922

View details for PubMedCentralID PMC4542721
Frozen blastocyst embryo transfer using a supplemented natural cycle protocol has a similar live birth rate compared to a programmed cycle protocol JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Lathi, R. B., Chi, Y., Liu, J., Saravanabavanandhan, B., Hegde, A., Baker, V. L. 2015; 32 (7): 1057-1062

Abstract

The purpose of this study is to compare outcomes for a supplemented natural cycle with a programmed cycle protocol for frozen blastocyst transfer.A retrospective analysis was performed of frozen autologous blastocyst transfers, at a single academic fertility center (519 supplemented natural cycles and 106 programmed cycles). Implantation, clinical pregnancy, miscarriage, and live birth and birth weight were compared using Pearson's Chi-squared test, T-test, or Fisher's exact test.There was no significant difference between natural and programmed frozen embryo transfers with respect to implantation (21.9 vs. 18.1 %), clinical pregnancy (35.5 vs. 29.2 %), and live birth rates (27.7 vs. 23.6 %). Mean birth weights were also similar between natural and programmed cycles for singletons (3354 vs. 3340 g) and twins (2422 vs. 2294 g)Frozen blastocyst embryo transfers using supplemented natural or programmed protocols experience similar success rates. Patient preference should be considered in choosing a protocol.

View details for DOI 10.1007/s10815-015-0499-x

View details for Web of Science ID 000359454000008

View details for PubMedID 26018319

View details for PubMedCentralID PMC4531857
Aneuploidy rates and blastocyst formation after biopsy of morulae and early blastocysts on day 5. Journal of assisted reproduction and genetics Kort, J. D., Lathi, R. B., Brookfield, K., Baker, V. L., Zhao, Q., Behr, B. R. 2015; 32 (6): 925-930

Abstract

Studies have demonstrated high implantation rates after trophectoderm biopsy of day 5 expanded blastocysts. However, biopsy of cleavage stage embryos may adversely affect embryo development and implantation. No studies have assessed the utility of day 5 morulae and early blastocyst biopsy. This study sought to better understand these slower embryos' aneuploidy rates and implantation potential.This was a retrospective review of all autologous IVF cycles utilizing PGS at a single academic infertility center.The biopsy of day 5 morulae and early blastocysts provided 22 % additional euploid blastocysts available for fresh day 6 transfer compared to day 5 biopsy of only expanded blastocysts. Aneuploidy did correlate with embryo stage on day 5, even after controlling for maternal age, with 16 % of morulae and 35 % of blastocysts being euploid. The majority (83 %) of euploid morulae progressed to the blastocyst stage by day 6. Experience transferring slower developing embryos is limited, but preliminary pregnancy and implantation rates appear similar to euploid embryos biopsied as expanded blastocysts.The biopsy of all non-arrested embryos on day 5 provides genetic information for all blastocysts on day 6, increasing the pool of euploid blastocysts available for fresh transfer and avoiding the need to cryopreserve developmentally competent embryos without genetic information.

View details for DOI 10.1007/s10815-015-0475-5

View details for PubMedID 25921084

View details for PubMedCentralID PMC4491071
Application of a validated prediction model for in vitro fertilization: comparison of live birth rates and multiple birth rates with 1 embryo transferred over 2 cycles vs 2 embryos in 1 cycle AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Barbara, L., Brown, M. B., Wantman, E., Stern, J. E., Baker, V. L., Widra, E., Coddington, C. C., Gibbons, W. E., Van Voorhis, B. J., Ball, G. D. 2015; 212 (5)

View details for DOI 10.1016/j.ajog.2015.02.005

View details for Web of Science ID 000353598500039
Application of a validated prediction model for in vitro fertilization: comparison of live birth rates and multiple birth rates with 1 embryo transferred over 2 cycles vs 2 embryos in 1 cycle. American journal of obstetrics and gynecology Luke, B., Brown, M. B., Wantman, E., Stern, J. E., Baker, V. L., Widra, E., Coddington, C. C., Gibbons, W. E., Van Voorhis, B. J., Ball, G. D. 2015; 212 (5): 676 e1-7

Abstract

The purpose of this study was to use a validated prediction model to examine whether single embryo transfer (SET) over 2 cycles results in live birth rates (LBR) comparable with 2 embryos transferred (DET) in 1 cycle and reduces the probability of a multiple birth (ie, multiple birth rate [MBR]).Prediction models of LBR and MBR for a woman considering assisted reproductive technology developed from linked cycles from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System for 2006-2012 were used to compare SET over 2 cycles with DET in 1 cycle. The prediction model was based on a woman's age, body mass index (BMI), gravidity, previous full-term births, infertility diagnoses, embryo state, number of embryos transferred, and number of cycles.To demonstrate the effect of the number of embryos transferred (1 or 2), the LBRs and MBRs were estimated for women with a single infertility diagnosis (male factor, ovulation disorders, diminished ovarian reserve, and unexplained); nulligravid; BMI of 20, 25, 30, and 35 kg/m2; and ages 25, 35, and 40 years old by cycle (first or second). The cumulative LBR over 2 cycles with SET was similar to or better than the LBR with DET in a single cycle (for example, for women with the diagnosis of ovulation disorders: 35 years old; BMI, 30 kg/m2; 54.4% vs 46.5%; and for women who are 40 years old: BMI, 30 kg/m(2); 31.3% vs 28.9%). The MBR with DET in 1 cycle was 32.8% for women 35 years old and 20.9% for women 40 years old; with SET, the cumulative MBR was 2.7% and 1.6%, respectively.The application of this validated predictive model demonstrated that the cumulative LBR is as good as or better with SET over 2 cycles than with DET in 1 cycle, while greatly reducing the probability of a multiple birth.

View details for DOI 10.1016/j.ajog.2015.02.005

View details for PubMedID 25683965
Association of number of retrieved oocytes with live birth rate and birth weight: an analysis of 231,815 cycles of in vitro fertilization FERTILITY AND STERILITY Baker, V. L., Brown, M. B., Luke, B., Conrad, K. P. 2015; 103 (4): 931-U101

Abstract

To determine if number of retrieved oocytes correlates with live birth rate and incidence of low birth weight (LBW).Retrospective cohort.Not applicable.Women undergoing fresh embryo transfer with the use of either autologous (n = 194,627) or donor (n = 37,188) oocytes whose cycles were reported to the Society for Assisted Reproductive Technology in the years 2004-2010.None.Live birth rate, birth weight, birth weight z-score, LBW.For both autologous and donor oocyte cycles, increasing number of retrieved oocytes paralleled live birth rate and embryos available for cryopreservation in most analyses, with all models adjusted for age and previous births. For cycles achieving singleton pregnancy with the use of autologous oocytes via transfer of two embryos, a higher number of retrieved oocytes was associated with lower mean birth weight, lower birth weight z-score, and greater incidence of LBW. In contrast, for cycles using donor oocytes, there was no association of number of retrieved oocytes with measures of birth weight.A higher number of retrieved oocytes was associated with an increased incidence of LBW in autologous singleton pregnancies resulting from transfer of two embryos, but not in donor oocyte cycles. Although the effect of high oocyte number on the incidence of LBW in autologous cycles was of modest magnitude, further study is warranted to determine if a subgroup of women may be particularly vulnerable.

View details for DOI 10.1016/j.fertnstert.2014.12.120

View details for Web of Science ID 000352110400020

View details for PubMedID 25638421
Assessment of multiple intrauterine gestations from ovarian stimulation (AMIGOS) trial: baseline characteristics FERTILITY AND STERILITY Diamond, M. P., Legro, R. S., Coutifaris, C., Alvero, R., Robinson, R. D., Casson, P., Christman, G. M., Ager, J., Huang, H., Hansen, K. R., Baker, V., Usadi, R., Seungdamrong, A., Bates, G. W., Rosen, R. M., Haisonleder, D., Krawetz, S. A., Barnhart, K., Trussell, J. C., Jin, Y., Santoro, N., Eisenberg, E., Zhang, H. 2015; 103 (4): 962-U143

Abstract

To identify baseline characteristics of women with unexplained infertility to determine whether treatment with an aromatase inhibitor will result in a lower rate of multiple gestations than current standard ovulation induction medications.Randomized, prospective clinical trial.Multicenter university-based clinical practices.A total of 900 couples with unexplained infertility.Collection of baseline demographics, blood samples, and ultrasonographic assessments.Demographic, laboratory, imaging, and survey characteristics.Demographic characteristics of women receiving clomiphene citrate (CC), letrozole, or gonadotropins for ovarian stimulation were very consistent. Their mean age was 32.2 ± 4.4 years and infertility duration was 34.7 ± 25.7 months, with 59% primary infertility. More than one-third of the women were current or past smokers. The mean body mass index (BMI) was 27 and mean antimüllerian hormone level was 2.6; only 11 women (1.3%) had antral follicle counts of <5. Similar observations were identified for hormonal profiles, ultrasound characterization of the ovaries, semen parameters, and quality of life assessments in both male and female partners.The cause of infertility in the couples recruited to this treatment trial is elusive, as the women were regularly ovulating and had evidence of good ovarian reserve both by basal FSH, antimüllerian hormone levels, and antral follicle counts; the male partners had normal semen parameters. The three treatment groups have common baseline characteristics, thereby providing comparable patient populations for testing the hypothesis that use of letrozole for ovarian stimulation can reduce the rates of multiples from that observed with gonadotropin and CC treatment.NCT 01044862.

View details for DOI 10.1016/j.fertnstert.2014.12.130

View details for Web of Science ID 000352110400024

View details for PubMedID 25707331
Computer-automated time-lapse analysis results correlate with embryo implantation and clinical pregnancy: A blinded, multi-centre study REPRODUCTIVE BIOMEDICINE ONLINE VerMilyea, M. D., Tan, L., Anthony, J. T., Conaghan, J., Ivani, K., Gvakharia, M., Boostanfar, R., Baker, V. L., Suraj, V., Chen, A. A., Mainigi, M., Coutifaris, C., Shen, S. 2014; 29 (6): 729-736

Abstract

Computer-automated time-lapse analysis has been shown to improve embryo selection by providing quantitative and objective information to supplement traditional morphology. In this multi-centre study, the relationship between such computer-derived outputs (High, Medium, Low scores), embryo implantation and clinical pregnancy were examined. Data were collected from six clinics, including 205 patients whose embryos were imaged by the Eeva(TM) System. The Eeva scores were blinded and not considered during embryo selection. Embryos with High and Medium scores had significantly higher implantation rates than those with Low scores (37% and 35% versus 15%; P < 0.0001; P = 0.0004). Similar trends in implantation rates were observed in different IVF centres each using their own protocols. Further analysis revealed that patients with at least one High embryo transferred had significantly higher clinical pregnancy rates than those with only Low embryos transferred (51% versus 34%; P = 0.02), although patients' clinical characteristics across groups were comparable. These data, together with previous research and clinical studies, confirm that computer-automated Eeva scores provide valuable information, which may improve the clinical outcome of IVF procedures and ultimately facilitate the trend of single embryo selection.

View details for DOI 10.1016/j.rbmo.2014.09.005

View details for Web of Science ID 000345759300011

View details for PubMedID 25444507
A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization. Human reproduction Baker, V. L., Jones, C. A., Doody, K., Foulk, R., Yee, B., Adamson, G. D., Cometti, B., DeVane, G., Hubert, G., Trevisan, S., Hoehler, F., Jones, C., Soules, M. 2014; 29 (10): 2212-2220

Abstract

Is the ongoing pregnancy rate with a new aqueous formulation of subcutaneous progesterone (Prolutex(®)) non-inferior to vaginal progesterone (Endometrin(®)) when used for luteal phase support of in vitro fertilization?In the per-protocol (PP) population, the ongoing pregnancy rates per oocyte retrieval at 12 weeks of gestation were comparable between Prolutex and Endometrin (41.6 versus 44.4%), with a difference between groups of -2.8% (95% confidence interval (CI) -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support.Luteal phase support has been clearly demonstrated to improve pregnancy rates in women undergoing in vitro fertilization (IVF). Because of the increased risk of ovarian hyperstimulation syndrome associated with the use of hCG, progesterone has become the treatment of choice for luteal phase support.This prospective, open-label, randomized, controlled, parallel-group, multicentre, two-arm, non-inferiority study was performed at eight fertility clinics. A total of 800 women, aged 18-42 years, with a BMI of ≤ 30 kg/m(2), with <3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2-3) FSH of ≤ 15 IU/L and undergoing IVF at 8 centres (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011.In total, 800 women undergoing IVF were randomized after retrieval of at least three oocytes to an aqueous preparation of progesterone administered subcutaneously (25 mg daily) or vaginal progesterone (100 mg bid daily). Randomization was performed to enrol 100 patients at each site using a randomization list that was generated with Statistical Analysis Software (SAS(®)). If a viable pregnancy occurred, progesterone treatment was continued up to 12 weeks of gestation.Using a PP analysis, which included all patients who received an embryo transfer (Prolutex = 392; Endometrin = 390), the ongoing pregnancy rate per retrieval for subcutaneous versus vaginal progesterone was 41.6 versus 44.4%, with a difference between groups of -2.8% (95% CI -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. In addition, rates of initial positive β-hCG (56.4% subcutaneous versus 59.0% vaginal; 95% CI -9.5, 4.3), clinical intrauterine pregnancy with fetal cardiac activity (42.6 versus 46.4%; 95% CI -10.8, 3.2), implantation defined as number of gestational sacs divided by number of embryos transferred (33.2 versus 35.1%; 95% CI -7.6, 4.0), live birth (41.1 versus 43.1%; 95% CI -8.9, 4.9) and take-home baby (41.1 versus 42.6%; 95% CI -8.4, 5.4) were comparable. Both formulations were well-tolerated, with no difference in serious adverse events. Analysis with the intention-to-treat population also demonstrated no difference for any outcomes between the treatment groups.The conclusions are limited to the progesterone dosing regimen studied and duration of treatment for the patient population examined in this study.Subcutaneous progesterone represents a novel option for luteal phase support in women undergoing IVF who for personal reasons prefer not to use a vaginal preparation or who wish to avoid the side effects of vaginal or i.m. routes of administration.The study was funded by Institut Biochimique SA (IBSA). CAJ, BC, ST and CJ are employees of IBSA. FH currently consults for IBSA.NCT00828191.

View details for DOI 10.1093/humrep/deu194

View details for PubMedID 25100106
A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization HUMAN REPRODUCTION Baker, V. L., Jones, C. A., Doody, K., Foulk, R., Yee, B., Adamson, G. D., Cometti, B., DeVane, G., Hubert, G., Trevisan, S., Hoehler, F., Jones, C., Soules, M. 2014; 29 (10): 2212-2220

View details for DOI 10.1093/humrep/deu194

View details for Web of Science ID 000343418500015
AMH in women with diminished ovarian reserve: potential differences by FMR1 CGG repeat level. Journal of assisted reproduction and genetics Pastore, L. M., McMurry, T. L., Williams, C. D., Baker, V. L., Young, S. L. 2014; 31 (10): 1295-1301

Abstract

We explored whether AMH, as a surrogate for oocyte supply, varies by FMR1 genotype in women diagnosed with diminished ovarian reserve (DOR), a subset of the Primary Ovarian Insufficiency phenotype. Research is inconsistent on the relationship between AMH and FMR1 repeat length, controlling for age.Seventy-nine cycling women diagnosed with DOR, and without a family history of fragile X syndrome, provided blood for FMR1 and AMH testing. DOR was defined as elevated FSH and/or low AMH and/or low antral follicle count, with regular menses. FMR1 CGG repeats were stratified by the larger allele <35 repeats (n = 70) v. ≥35 repeats (n = 9). Quadratic and linear models were fit to predict log (AMH) controlling for age. The AMH sample used as the outcome variable was drawn at a later date than the diagnostic AMH.Serum AMH concentration median was 0.30 ng/mL; Ages ranged from 26-43 years. A quadratic model (including age(2)) did not show a relationship with FMR1 CGG level (p-value = 0.25). A linear model of log (AMH), corresponding to an exponential decline of AMH with increasing age, was significantly different, and had a steeper slope, for women with ≥ 35 CGG repeats than women with < 35 repeats (p = 0.035).Findings suggest a greater rate of follicular loss that starts at later ages in women with DOR and ≥ 35 CGG repeats.

View details for DOI 10.1007/s10815-014-0276-2

View details for PubMedID 24938362
AMH in women with diminished ovarian reserve: potential differences by FMR1 CGG repeat level JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Pastore, L. M., McMurry, T. L., Williams, C. D., Baker, V. L., Young, S. L. 2014; 31 (10): 1295-1301

Abstract

We explored whether AMH, as a surrogate for oocyte supply, varies by FMR1 genotype in women diagnosed with diminished ovarian reserve (DOR), a subset of the Primary Ovarian Insufficiency phenotype. Research is inconsistent on the relationship between AMH and FMR1 repeat length, controlling for age.Seventy-nine cycling women diagnosed with DOR, and without a family history of fragile X syndrome, provided blood for FMR1 and AMH testing. DOR was defined as elevated FSH and/or low AMH and/or low antral follicle count, with regular menses. FMR1 CGG repeats were stratified by the larger allele <35 repeats (n = 70) v. ≥35 repeats (n = 9). Quadratic and linear models were fit to predict log (AMH) controlling for age. The AMH sample used as the outcome variable was drawn at a later date than the diagnostic AMH.Serum AMH concentration median was 0.30 ng/mL; Ages ranged from 26-43 years. A quadratic model (including age(2)) did not show a relationship with FMR1 CGG level (p-value = 0.25). A linear model of log (AMH), corresponding to an exponential decline of AMH with increasing age, was significantly different, and had a steeper slope, for women with ≥ 35 CGG repeats than women with < 35 repeats (p = 0.035).Findings suggest a greater rate of follicular loss that starts at later ages in women with DOR and ≥ 35 CGG repeats.

View details for DOI 10.1007/s10815-014-0276-2

View details for Web of Science ID 000342430700006

View details for PubMedCentralID PMC4171418
A prediction model for live birth and multiple births within the first three cycles of assisted reproductive technology. Fertility and sterility Luke, B., Brown, M. B., Wantman, E., Stern, J. E., Baker, V. L., Widra, E., Coddington, C. C., Gibbons, W. E., Ball, G. D. 2014; 102 (3): 744-752

Abstract

To develop a model predictive of live-birth rates (LBR) and multiple birth rates (MBR) for an individual considering assisted reproduction technology (ART) using linked cycles from Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) for 2004-2011.Longitudinal cohort.Clinic-based data.288,161 women with an initial autologous cycle, of whom 89,855 did not become pregnant and had a second autologous cycle and 39,334 did not become pregnant in the first and second cycles and had a third autologous cycle, with an additional 33,598 women who had a cycle using donor oocytes (first donor cycle).None.LBRs and MBRs modeled by woman's age, body mass index, gravidity, prior full-term births, infertility diagnoses by oocyte source, fresh embryos transferred, and cycle, using backward-stepping logistic regression with results presented as adjusted odds ratios (AORs) and 95% confidence intervals.The LBRs increased in all models with prior full-term births, number of embryos transferred; in autologous cycles also with gravidity, diagnoses of male factor, and ovulation disorders; and in donor cycles also with the diagnosis of diminished ovarian reserve. The MBR increased in all models with number of embryos transferred and in donor cycles also with prior full-term births. For both autologous and donor cycles, transferring two versus one embryo greatly increased the probability of a multiple birth (AOR 27.25 and 38.90, respectively).This validated predictive model will be implemented on the Society for Assisted Reproductive Technology Web site (www.sart.org) so that patients considering initiating a course of ART can input their data on the Web site to generate their expected outcomes.

View details for DOI 10.1016/j.fertnstert.2014.05.020

View details for PubMedID 24934487
Maximizing the clinical utility of antimüllerian hormone testing in women's health. Current opinion in obstetrics & gynecology Leader, B., Baker, V. L. 2014; 26 (4): 226-236

Abstract

To provide an update on the latest clinical applications of serum antimüllerian hormone (AMH) testing with practical approaches to mitigate the impact of significant variability in AMH results.Recent studies continue to demonstrate that AMH is the best single serum test for ovarian response management with, at most, a weak-to-moderate age-independent association with live-birth rate and time to conception. Data confirm serum AMH levels improve menopause prediction, monitoring of ovarian damage, and identification of women at risk for several ovary-related disorders such as polycystic ovary syndrome and premature or primary ovarian insufficiency. However, it is now recognized that serum AMH results can have dramatic variability due to common, biologic fluctuations within some individuals, use of hormonal contraceptives or other medications, certain surgical procedures, specimen treatment, assay changes, and laboratory calibration differences. Practical guidelines are provided to minimize the impact of variability in AMH results and maximize the accuracy of clinical decision-making.AMH is an ovarian biomarker of central importance which improves the clinical management of women's health. However, with the simultaneous rapid expansion of AMH clinical applications and recognition of variability in AMH results, consensus regarding the clinical cutpoints is increasingly difficult. Therefore, a careful approach to AMH measurement and interpretation in clinical care is essential.

View details for DOI 10.1097/GCO.0000000000000087

View details for PubMedID 24978853
Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. New England journal of medicine Legro, R. S., Brzyski, R. G., Diamond, M. P., Coutifaris, C., Schlaff, W. D., Casson, P., Christman, G. M., Huang, H., Yan, Q., Alvero, R., Haisenleder, D. J., Barnhart, K. T., Bates, G. W., Usadi, R., Lucidi, S., Baker, V., Trussell, J. C., Krawetz, S. A., Snyder, P., Ohl, D., Santoro, N., Eisenberg, E., Zhang, H. 2014; 371 (2): 119-129

Abstract

Clomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome, but aromatase inhibitors, including letrozole, might result in better pregnancy outcomes.In this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries). Participants were 18 to 40 years of age, had at least one patent fallopian tube and a normal uterine cavity, and had a male partner with a sperm concentration of at least 14 million per milliliter; the women and their partners agreed to have regular intercourse with the intent of conception during the study. The primary outcome was live birth during the treatment period.Women who received letrozole had more cumulative live births than those who received clomiphene (103 of 374 [27.5%] vs. 72 of 376 [19.1%], P=0.007; rate ratio for live birth, 1.44; 95% confidence interval, 1.10 to 1.87) without significant differences in overall congenital anomalies, though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group (P=0.65). The cumulative ovulation rate was higher with letrozole than with clomiphene (834 of 1352 treatment cycles [61.7%] vs. 688 of 1425 treatment cycles [48.3%], P<0.001). There were no significant between-group differences in pregnancy loss (49 of 154 pregnancies in the letrozole group [31.8%] and 30 of 103 pregnancies in the clomiphene group [29.1%]) or twin pregnancy (3.4% and 7.4%, respectively). Clomiphene was associated with a higher incidence of hot flushes, and letrozole was associated with higher incidences of fatigue and dizziness. Rates of other adverse events were similar in the two treatment groups.As compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.).

View details for DOI 10.1056/NEJMoa1313517

View details for PubMedID 25006718
Letrozole versus Clomiphene for Infertility in the Polycystic Ovary Syndrome NEW ENGLAND JOURNAL OF MEDICINE Legro, R. S., Brzyski, R. G., Diamond, M. P., Coutifaris, C., Schlaff, W. D., Casson, P., Christman, G. M., Huang, H., Yan, Q., Alvero, R., Haisenleder, D. J., Barnhart, K. T., Bates, G. W., Usadi, R., Lucidi, S., Baker, V., Trussell, J. C., Krawetz, S. A., Snyder, P., Ohl, D., Santoro, N., Eisenberg, E., Zhang, H. 2014; 371 (2): 119-129

View details for DOI 10.1056/NEJMoa1313517

View details for Web of Science ID 000338645500008
Conjugated bisphenol A in maternal serum in relation to miscarriage risk. Fertility and sterility Lathi, R. B., Liebert, C. A., Brookfield, K. F., Taylor, J. A., vom Saal, F. S., Fujimoto, V. Y., Baker, V. L. 2014; 102 (1): 123-128

Abstract

To examine the relationship between the maternal serum bisphenol A (BPA) concentration at the time of the missed menstrual cycle and miscarriage risk.Retrospective cohort of prospectively collected serum samples.Academic fertility center.Women presenting for early pregnancy monitoring with singleton pregnancies.Stored serum samples from 4 to 5 weeks' gestation analyzed for conjugated serum BPA concentrations.Live birth, miscarriage, and chromosome content of miscarriage.With the 115 women included in the study, there were 47 live births and 68 clinical miscarriages (46 aneuploid and 22 euploid). Median conjugated BPA concentrations were higher in the women who had miscarriages than in those who had live births (0.101 vs. 0.075 ng/mL). Women with the highest quartile of conjugated BPA had an increased relative risk of miscarriage (1.83; 95% CI, 1.14-2.96) compared with the women in the lowest quartile. We found a similar increase risk for both euploid and aneuploid miscarriages.Maternal conjugated BPA was associated with a higher risk of aneuploid and euploid miscarriage in this cohort. The impact of reducing individual exposure on future pregnancy outcomes deserves further study.

View details for DOI 10.1016/j.fertnstert.2014.03.024

View details for PubMedID 24746738
Preimplantation diagnosis for single gene disorders. Seminars in reproductive medicine Berger, V. K., Baker, V. L. 2014; 32 (2): 107-113

Abstract

Preimplantation genetic diagnosis (PGD) allows patients who are carriers or who are affected by genetic diseases to select unaffected embryos for transfer before becoming pregnant. The practice of PGD is evolving with rapid advances in technology and biopsy methods. Testing for a specific gene mutation can be performed in combination with 24-chromosome aneuploidy screening. Several unique applications of PGD are reviewed, including exclusion diagnosis for couples from Huntington disease families, testing for fragile X premutations, and human leukocyte antigen matching for stem cell donor siblings. Although PGD for single gene mutations allows patients to gain information about their embryos and perhaps avoid a difficult decision about whether or not to terminate an ongoing pregnancy, this technique also provides for much ethical debate encompassing the well-being of the prospective couple, embryo, child, and people in the community affected by the diseases being screened.

View details for DOI 10.1055/s-0033-1363552

View details for PubMedID 24515905
The Pregnancy in Polycystic Ovary Syndrome II study: baseline characteristics and effects of obesity from a multicenter randomized clinical trial FERTILITY AND STERILITY Legro, R. S., Brzyski, R. G., Diamond, M. P., Coutifaris, C., Schlaff, W. D., Alvero, R., Casson, P., Christman, G. M., Huang, H., Yan, Q., Haisenleder, D. J., Barnhart, K. T., Bates, G. W., Usadi, R., Lucidi, R., Baker, V., Trussell, J. C., Krawetz, S. A., Snyder, P., Ohl, D., Santoro, N., Eisenberg, E., Zhang, H. 2014; 101 (1): 258-?

Abstract

To summarize baseline characteristics from a large multicenter infertility clinical trial.Cross-sectional baseline data from a double-blind randomized trial of two treatment regimens (letrozole vs. clomiphene).Academic Health Centers throughout the United States.Seven hundred fifty women with polycystic ovary syndrome (PCOS) and their male partners took part in the study.None.Historic, biometric, biochemical, and questionnaire parameters.Females averaged 30 years and were obese (body mass index [BMI] 35) with ∼20% from a racial/ethnic minority. Most (87%) were hirsute and nulligravid (63%). Most of the women had an elevated antral follicle count and enlarged ovarian volume on ultrasound. Women had elevated mean circulating androgens, LH-to-FSH ratio (∼2), and antimüllerian hormone levels (8.0 ng/mL). In addition, women had evidence for metabolic dysfunction with elevated mean fasting insulin and dyslipidemia. Increasing obesity was associated with decreased LH-to-FSH levels, antimüllerian hormone levels, and antral follicle counts but increasing cardiovascular risk factors, including prevalence of the metabolic syndrome. Men were obese (BMI 30) and had normal mean semen parameters.The treatment groups were well matched at baseline. Obesity exacerbates select female reproductive and most metabolic parameters. We have also established a database and sample repository that will eventually be accessible to investigators.NCT00719186.

View details for DOI 10.1016/j.fertnstert.2013.08.056

View details for Web of Science ID 000329128800049

View details for PubMedID 24156957

View details for PubMedCentralID PMC3899700
Second try: who returns for additional assisted reproductive technology treatment and the effect of a prior assisted reproductive technology birth FERTILITY AND STERILITY Luke, B., Brown, M. B., Wantman, E., Baker, V. L., Grow, D. R., Stern, J. E. 2013; 100 (6): 1580-1584

Abstract

To evaluate the effect of a prior assisted reproductive technology (ART) live birth on subsequent live-birth rates.Historical cohort study.Clinic-based data.The study population included 297,635 women with 549,278 cycles from 2004 to 2010 from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System. Try 1 refers to ART cycles up to and including the first live birth, try 2 to ART cycles after a first live birth.None.Live-birth rates by cycle number, try number, and oocyte source.Younger women at try 1 are more likely to return for try 2. Women returning for try 2 were more likely to have had an ART singleton versus multiple birth (33.2% after a try 1 singleton versus 8.1% after twins and 4.9% after triplets) and were less likely to have a diagnosis of diminished ovarian reserve or tubal factors. Live-birth rates were significantly higher for try 2 compared with try 1 for autologous fresh cycles, averaging 7.7 percentage points higher over five cycles. Live-birth rates were not significantly different for try 2 versus try 1 with thawed autologous cycles or either fresh or thawed donor cycles.These results indicate that when fresh autologous oocytes can be used, live-birth rates per cycle are significantly greater after a prior history of an ART live birth.

View details for DOI 10.1016/j.fertnstert.2013.07.1993

View details for Web of Science ID 000327533000024

View details for PubMedID 23987515
Primary ovarian insufficiency in the adolescent CURRENT OPINION IN OBSTETRICS & GYNECOLOGY Baker, V. L. 2013; 25 (5): 375-381

Abstract

To raise awareness about the importance of early diagnosis of primary ovarian insufficiency (POI) in the adolescent.Menstrual cycle irregularity or amenorrhea in the adolescent has historically been treated with oral contraceptives or ignored, with no evaluation done to determine the cause. However, it is now becoming clear that the health consequences of menstrual irregularities differ depending on the cause, and evaluation to determine the cause of menstrual irregularity is warranted. Although POI is classically diagnosed when menstrual cycle irregularity is accompanied by high circulating levels of gonadotropins and low estradiol, anti-Mullerian hormone is emerging as a biomarker of increasing importance. When POI is diagnosed, further evaluation including karyotype, FMR1 premutation analysis, and 21-hydroxylase or adrenal antibody is warranted. Girls at high risk for the development of POI (e.g. because of planned cancer treatment) should be offered the option of oocyte or ovarian tissue cryopreservation.POI should be ruled out in adolescents with menstrual cycle irregularity. Early diagnosis of POI facilitates the individualization of therapy, as the health consequences of POI differ from those of other causes of menstrual cycle irregularity. In addition, recognition of premature oocyte depletion allows for the option of fertility preservation to be discussed when oocytes are still present.

View details for DOI 10.1097/GCO.0b013e328364ed2a

View details for Web of Science ID 000326586300006

View details for PubMedID 24018874
Improving embryo selection using a computer-automated time-lapse image analysis test plus day 3 morphology: results from a prospective multicenter trial FERTILITY AND STERILITY Conaghan, J., Chen, A. A., Willman, S. P., Ivani, K., Chenette, P. E., Boostanfar, R., Baker, V. L., Adamson, G. D., Abusief, M. E., Gvakharia, M., Loewke, K. E., Shen, S. 2013; 100 (2): 412-?

Abstract

To assess the first computer-automated platform for time-lapse image analysis and blastocyst prediction and to determine how the screening information may assist embryologists in day 3 (D3) embryo selection.Prospective, multicenter, cohort study.Five IVF clinics in the United States.One hundred sixty women ≥18 years of age undergoing fresh IVF treatment with basal antral follicle count ≥8, basal FSH <10 IU/mL, and ≥8 normally fertilized oocytes.A noninvasive test combining time-lapse image analysis with the cell-tracking software, Eeva (Early Embryo Viability Assessment), was used to measure early embryo development and generate usable blastocyst predictions by D3.Improvement in the ability of experienced embryologists to select which embryos are likely to develop to usable blastocysts using D3 morphology alone, compared with morphology plus Eeva.Experienced embryologists using Eeva in combination with D3 morphology significantly improved their ability to identify embryos that would reach the usable blastocyst stage (specificity for each of three embryologists using morphology vs. morphology plus Eeva: 59.7% vs. 86.3%, 41.9% vs. 84.0%, 79.5% vs. 86.6%). Adjunctive use of morphology plus Eeva improved embryo selection by enabling embryologists to better discriminate which embryos would be unlikely to develop to blastocyst and was particularly beneficial for improving selection among good-morphology embryos. Adjunctive use of morphology plus Eeva also reduced interindividual variability in embryo selection.Previous studies have shown improved implantation rates for blastocyst transfer compared with cleavage-stage transfer. Addition of Eeva to the current embryo grading process may improve the success rates of cleavage-stage ETs.

View details for DOI 10.1016/j.fertnstert.2013.04.021

View details for Web of Science ID 000322633200028

View details for PubMedID 23721712
Frequency of the Male Infertility Evaluation: Data from the National Survey of Family Growth JOURNAL OF UROLOGY Eisenberg, M. L., Lathi, R. B., Baker, V. L., Westphal, L. M., Milki, A. A., Nangia, A. K. 2013; 189 (3): 1030-1034

Abstract

An estimated 7 million American couples per year seek infertility care in the United States. A male factor contributes to 50% of cases but it is unclear what proportion of infertile couples undergoes male evaluation.We analyzed data from cycles 5 to 7 of the National Survey of Family Growth performed by the Centers for Disease Control to determine the frequency of a male infertility evaluation, and associated reproductive and demographic factors.A total of 25,846 women and 11,067 men were surveyed. Male evaluation was not completed in 18% of couples when the male partner was asked vs 27% when female partners were asked. This corresponds to approximately 370,000 to 860,000 men in the population who were not evaluated at the time of infertility evaluation. Longer infertility duration and white race were associated with increased odds of male infertility evaluation. The male and female samples showed no change in the receipt of male examination with time.Many men from infertile couples do not undergo male evaluation in the United States. Given the potential implications to reproductive goals and male health, further examination of this pattern is warranted.

View details for DOI 10.1016/j.juro.2012.08.239

View details for Web of Science ID 000315109600076

View details for PubMedID 23009868
Mild ovarian stimulation for in vitro fertilization: one perspective from the USA JOURNAL OF ASSISTED REPRODUCTION AND GENETICS Baker, V. L. 2013; 30 (2): 197-202

Abstract

To provide a perspective regarding mild ovarian stimulation, taking into account particular issues relevant in the United StatesLiterature review and editorial commentaryMild ovarian stimulation for IVF has some proven and some theoretical advantages over conventional stimulation, such as lower risk of ovarian hyperstimulation syndrome and lower cost per fresh IVF cycle. However, cumulative live birth rate, including transfers from fresh and frozen embryos, is likely to be lower with mild stimulation. The cost-effectiveness of mild stimulation IVF in the United States has not been established.Mild ovarian stimulation is an appropriate option to consider for certain patient groups or based on patient preference. However, significant potential disadvantages limit its widespread acceptability for patients in the United States at this time.

View details for DOI 10.1007/s10815-013-9946-8

View details for Web of Science ID 000315576000005

View details for PubMedID 23381553
Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies\ AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY Conrad, K. P., Baker, V. L. 2013; 304 (2): R69-R72

Abstract

Investigations in the rat model of pregnancy indicate an important role for the corpus luteal (CL) hormone relaxin in the maternal circulatory and osmoregulatory changes in pregnancy, which are epitomized by profound vasodilation and modest hypoosmolality, respectively. In a pilot study of infertile women who became pregnant through donor eggs, in vitro fertilization, and embryo transfer, the gestational rise in glomerular filtration and fall in plasma osmolality were markedly subdued. Because these women were infertile, they lacked a CL and circulating relaxin (and possibly other vasoactive CL hormones). Based on these findings in pregnant rats and women, we hypothesize that infertile women conceiving through donor eggs will have overall subdued circulatory changes (e.g., attenuated reduction in systemic vascular resistance and subdued increase in cardiac output) particularly during early pregnancy when CL hormones predominate before the full development and maturation of the placenta. In contrast, infertile women conceiving by autologous eggs retrieved after ovarian stimulation and fresh embryo transfer may have a relatively hyperdynamic circulation due to the presence of many CL (up to 20 or more) and higher circulating levels of vasodilatory ovarian hormones such as relaxin. Emerging evidence suggests that women undergoing Assisted Reproductive Technologies (ART) have increased risk for adverse pregnancy outcomes such as preeclampsia and small for gestational-age babies. This increased risk may be partly caused by the maternal milieu, which is not physiological in ART pregnancies due to the abnormal status of the CL.

View details for DOI 10.1152/ajpregu.00239.2012

View details for Web of Science ID 000313738800001

View details for PubMedID 23100030
Outcomes of trophectoderm biopsy on cryopreserved blastocysts: a case series REPRODUCTIVE BIOMEDICINE ONLINE Lathi, R. B., Massie, J. A., Gilani, M., Milki, A. A., Westphal, L. M., Baker, V. L., Behr, B. 2012; 25 (5): 504-507

Abstract

Preimplantation genetic diagnosis (PGD) is an increasingly common adjunct to IVF. The information gained from PGD may be used to reduce the incidence of chromosomally abnormal pregnancies and augment the current selection process of embryos. As such, patients may choose to utilize PGD in either fresh or cryopreserved IVF cycles. It is a common practice to cryopreserve excess embryos at the blastocyst stage. In these cases, trophectoderm biopsy is the only technique available for PGD. This articles reports this study centre's experience with trophectoderm biopsies of cryopreserved blastocysts in 12 patients who underwent 13 cycles of PGD. The implantation rate per embryo transferred was 46% and the ongoing pregnancy rate per embryo transfer was 63%. The results from this case series demonstrate that trophectoderm biopsy on cryopreserved blastocysts to perform PGD is logistically feasible. In addition, the rate of implantation and ongoing pregnancy were maintained within a reasonable range to justify the procedure. Preimplantation genetic diagnosis (PGD) is an increasingly common adjunct to IVF and is used to evaluate the genetic makeup of the embryo prior to transfer of the embryo into the uterus. The information gained from PGD may be used to identify single-gene disorders that result in genetic disease, reduce the incidence of chromosomally abnormal pregnancies and/or augment the selection process of embryos to be transferred. In order to perform PGD, a biopsy of the embryo is the performed and cells are removed for testing. PGD may be performed in either fresh or frozen (cryopreserved) IVF cycles. Patients who have cryopreserved embryos remaining in storage from a previous fresh cycle may wish to have these embryos tested with PGD. Many embryos are frozen on day 5 of development, referred to as the blastocyst stage. At this stage of development, embryo biopsy is performed via a technique known as 'trophectoderm biopsy', in which 1-3 of the cells destined to become the placenta are removed from the embryo for chromosomal testing. We report our experience with trophectoderm biopsy of frozen blastocysts in 12 patients who underwent 13 cycles of PGD. The implantation rate per embryo transferred was 46% and the ongoing pregnancy rate per embryo transfer was 63%. The results from this case series demonstrate that trophectoderm biopsy on cryopreserved blastocysts to perform PGD is logistically feasible. In addition, the rate of implantation and ongoing pregnancy were maintained within a reasonable range to justify the procedure.

View details for DOI 10.1016/j.rbmo.2012.06.021

View details for Web of Science ID 000310639600010

View details for PubMedID 22985500
Elevated Prevalence of 35-44 FMR1 Trinucleotide Repeats in Women With Diminished Ovarian Reserve REPRODUCTIVE SCIENCES Pastore, L. M., Young, S. L., Baker, V. L., Karns, L. B., Williams, C. D., Silverman, L. M. 2012; 19 (11): 1226-1231

Abstract

Fragile X premutations are associated with primary ovarian insufficiency when the patient presents with amenorrhea, but the fragile X mental retardation 1 (FMR1) CGG repeat count among cycling women with low ovarian reserve (diminished ovarian reserve [DOR]) is not yet established.Sixty-two infertile DOR patients were recruited from 4 US private and academic fertility centers.The prevalence of 35-44 FMR1 CGG repeats was 14.5%. Compared with the general female population estimate from the literature, infertile women with DOR were more likely to have 35-44 FMR1 CGG repeats (14.5% and 3.9%, respectively, P = .0003). Similar findings were noted by 5-repeat bandwidth: 35-39 CGG repeats (9.7% DOR vs 3.2% comparison, P = .012) or 40-44 CGG repeats (4.8% DOR vs 0.7% comparison, P = .024).These data suggest that CGG repeats of 35-44 may be markedly overrepresented in women with DOR, whereas the current FMR1 reference range indicates that there is no clinical phenotype with <45 CGG repeats.

View details for DOI 10.1177/1933719112446074

View details for Web of Science ID 000309713300011

View details for PubMedID 22581803
High frequency of discordance between antimullerian hormone and follicle-stimulating hormone levels in serum from estradiol-confirmed days 2 to 4 of the menstrual cycle from 5,354 women in U.S. fertility centers FERTILITY AND STERILITY Leader, B., Hegde, A., Baca, Q., Stone, K., Lannon, B., Seifer, D. B., Broekmans, F., Baker, V. L. 2012; 98 (4): 1037-1042

Abstract

To determine the frequency of clinical discordance between antimüllerian hormone (AMH, ng/mL) and follicle-stimulating hormone (FSH, IU/L) by use of cut points defined by response to controlled ovarian stimulation in the same serum samples drawn on estradiol-confirmed, menstrual cycle days 2 to 4.Retrospective analysis.Fertility centers in 30 U.S. states and a single reference laboratory with uniform testing protocols.5,354 women, 20 to 45 years of age.None.Frequency of discordance between serum AMH and FSH values.Of the 5,354 women tested, 1 in 5 had discordant AMH and FSH values defined as AMH <0.8 (concerning) with FSH <10 (reassuring) or AMH ≥ 0.8 (reassuring) with FSH ≥ 10 (concerning). Of the women with reassuring FSH values (n = 4,469), the concerning AMH values were found in 1 in 5 women in a highly age-dependent fashion, ranging from 1 in 11 women under 35 years of age to 1 in 3 women above 40 years of age. On the other hand, of the women with reassuring AMH values (n = 3,742), 1 in 18 had concerning FSH values, a frequency that did not vary in a statistically significant fashion by age.Clinical discordance in serum AMH and FSH values was frequent and age dependent using common clinical cut points, a large patient population, one reference laboratory, and uniform testing methodology. This conclusion is generalizable to women undergoing fertility evaluation, although AMH testing has not been standardized among laboratories, and the cut points presented are specific to the laboratory in this study.

View details for DOI 10.1016/j.fertnstert.2012.06.006

View details for Web of Science ID 000309553500050

View details for PubMedID 22771028
Race matters: a systematic review of racial/ethnic disparity in Society for Assisted Reproductive Technology reported outcomes FERTILITY AND STERILITY Wellons, M. F., Fujimoto, V. Y., Baker, V. L., Barrington, D. S., Broomfield, D., Catherino, W. H., Richard-Davis, G., Ryan, M., Thornton, K., Armstrong, A. Y. 2012; 98 (2): 406-409

Abstract

To systematically review the reporting of race/ethnicity in Society for Assisted Reproductive Technology (SART) Clinic Outcome Reporting System (CORS) publications.Systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology of literature published in PubMed on race/ethnicity that includes data from SART CORS.Not applicable.Not applicable.In vitro fertilization cycles reported to SART.Any outcomes reported in SART CORS.Seven publications were identified that assessed racial/ethnic disparities in IVF outcomes using SART data. All reported a racial/ethnic disparity. However, more than 35% of cycles were excluded from analysis because of missing race/ethnicity data.Review of current publications of SART data suggests significant racial/ethnic disparities in IVF outcomes. However, the potential for selection bias limits confidence in these findings, given that fewer than 65% of SART reported cycles include race/ethnicity. Our understanding of how race/ethnicity influences ART outcome could be greatly improved if information on race/ethnicity was available for all reported cycles.

View details for DOI 10.1016/j.fertnstert.2012.05.012

View details for Web of Science ID 000306975400026

View details for PubMedID 22698638
Executive summary of the Stages of Reproductive Aging Workshop+10: addressing the unfinished agenda of staging reproductive aging FERTILITY AND STERILITY Harlow, S. D., Gass, M., Hall, J. E., Lobo, R., Maki, P., Rebar, R. W., Sherman, S., Sluss, P. M., de Villiers, T. J. 2012; 97 (4): 843-851

Abstract

The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period.Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus.STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage -1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics.STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified.

View details for DOI 10.1016/j.fertnstert.2012.01.128

View details for Web of Science ID 000302143500013

View details for PubMedID 22341880
Executive summary of the Stages of Reproductive Aging Workshop+10: addressing the unfinished agenda of staging reproductive aging MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY Harlow, S. D., Gass, M., Hall, J. E., Lobo, R., Maki, P., Rebar, R. W., Sherman, S., Sluss, P. M., de Villiers, T. J. 2012; 19 (4): 387-395

Abstract

The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period.Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus.STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage -1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics.STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified.

View details for DOI 10.1097/gme.0b013e31824d8f40

View details for Web of Science ID 000302141700005

View details for PubMedID 22343510
Executive summary of the Stages of Reproductive Aging Workshop+10: addressing the unfinished agenda of staging reproductive aging CLIMACTERIC Harlow, S. D., Gass, M., Hall, J. E., Lobo, R., Maki, P., Rebar, R. W., Sherman, S., Sluss, P. M., de Villiers, T. J. 2012; 15 (2): 105-114

Abstract

The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW +10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period.Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus.STRAW +10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage -1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics.STRAW +10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW +10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified.

View details for DOI 10.3109/13697137.2011.650656

View details for Web of Science ID 000301532500002

View details for PubMedID 22338612
Executive Summary of the Stages of Reproductive Aging Workshop+10: Addressing the Unfinished Agenda of Staging Reproductive Aging JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Harlow, S. D., Gass, M., Hall, J. E., Lobo, R., Maki, P., Rebar, R. W., Sherman, S., Sluss, P. M., de Villiers, T. J. 2012; 97 (4): 1159-1168

Abstract

The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period.Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus.STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage -3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage -1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics.STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified.

View details for DOI 10.1210/jc.2011-3362

View details for Web of Science ID 000302787800041

View details for PubMedID 22344196
Early pregnancy testosterone after ovarian stimulation and pregnancy outcome FERTILITY AND STERILITY Gustin, S. L., Mukherjee, G., Baker, V. L., Westphal, L. M., Milki, A. A., Lathi, R. B. 2012; 97 (1): 23-U48

Abstract

To examine early pregnancy (EP) testosterone (T) after ovarian stimulation and its effect on singleton pregnancy outcomes.Prospective cohort study.University-based tertiary care center.Subfertile women who conceived with or without fertility treatment.Ovarian stimulation for assisted reproduction, collection of serum total T levels in early pregnancy, and pregnancy follow-up.Rate of preterm delivery, low birth weight (LBW) (<2,500 g), and hypertensive disorders of pregnancy.EP serum samples were measured from 266 singleton pregnancies. The mean T level among spontaneous conceptions was 74.90 ng/dL (SD 48.35 ng/dL); 103 ng/mL was the 90th percentile. Mean EP T was increased among patients who underwent ovarian stimulation compared with nonstimulated control subjects. In patients undergoing IVF, T levels in EP were linearly correlated with the number of oocytes retrieved. When pregnancy outcomes in women with normal T were compared with women with elevated T (>90th percentile), we did not see an increased risk for preterm delivery, hypertensive disorders of pregnancy, LBW infants, or cesarean delivery (odds ratio ratios 1.43, 0.38, 1.39, and 0.85, respectively).Elevations in EP T are associated with ovarian stimulation but do not appear to be associated with adverse pregnancy outcome. Further investigation to determine the etiology of increased maternal and neonatal morbidity among subfertile women is warranted.

View details for DOI 10.1016/j.fertnstert.2011.10.020

View details for Web of Science ID 000298367600009

View details for PubMedID 22112646
An assessment of female university students' attitudes toward screening technologies for ovarian reserve FERTILITY AND STERILITY Bavan, B., Porzig, E., Baker, V. L. 2011; 96 (5): 1195-1199

Abstract

To assess female university students' attitudes toward screening technologies for ovarian reserve and their potential influence on career and family planning decisions.Online survey.Not applicable.Respondents from 4 universities in Northern California.None.Proportion with interest in screening technologies for ovarian reserve.Of the 328 respondents, 79% were interested in learning about the current status of their ovarian reserve. Hypothetically, if informed that ovarian reserve was very low, 53% would consider oocyte cryopreservation (even when informed that it is experimental); however, only 29% would consider stopping educational or professional pursuits to focus on conceiving. Participants also demonstrated gaps in knowledge, believing that the decline in ovarian reserve starts later than it actually does, that diet and nutrition can preserve ovarian reserve, and that infertility treatments are highly effective regardless of how severe the depletion of the egg supply is.Women attending universities are interested in assessing their own ovarian reserve. Gaps in knowledge about ovarian reserve exist among these reproductive-aged women.

View details for DOI 10.1016/j.fertnstert.2011.08.018

View details for Web of Science ID 000296572000031

View details for PubMedID 21924717
Use of preimplantation genetic diagnosis and preimplantation genetic screening in the United States: a Society for Assisted Reproductive Technology Writing Group paper FERTILITY AND STERILITY Ginsburg, E. S., Baker, V. L., Racowsky, C., Wantman, E., Goldfarb, J., Stern, J. E. 2011; 96 (4): 865-868

Abstract

To comprehensively report Society for Assisted Reproductive Technology (SART) member program usage of preimplantation genetic testing (PGT), preimplantation genetic diagnosis (PGD) for diagnosis of specific conditions, and preimplantation genetic screening for aneuploidy (PGS).Retrospective study.United States SART cohort data.Women undergoing a PGT cycle in which at least one embryo underwent biopsy.PGT.PGT use, indications, and delivery rates.Of 190,260 fresh, nondonor assisted reproductive technology (ART) cycles reported to SART CORS in 2007-2008, 8,337 included PGT. Of 6,971 cycles with a defined indication, 1,382 cycles were for genetic diagnosis, 3,645 for aneuploidy screening (PGS), 527 for translocation, and 1,417 for elective sex election. Although the total number of fresh, autologous cycles increased by 3.6% from 2007 to 2008, the percentage of cycles with PGT decreased by 5.8% (4,293 in 2007 and 4,044 in 2008). As a percentage of fresh, nondonor ART cycles, use dropped from 4.6% (4,293/93,433) in 2007 to 4.2% (4,044/96,827) in 2008. The primary indication for PGT was PGS: cycles performed for this indication decreased (-8.0%). PGD use for single-gene defects (+3.2%), elective sex selection (+5.3%), and translocation analysis (+0.5%) increased. PGT usage varied significantly by geographical region.PGT usage in the United States decreased between 2007 and 2008 owing to a decrease in PGS. Use of elective sex selection increased. High transfer cancellation rates correlated with reduced live-birth rates for some PGT indications.

View details for DOI 10.1016/j.fertnstert.2011.07.1139

View details for Web of Science ID 000295938800022

View details for PubMedID 21872229
Life Plans and Family-Building Options for Women with Primary Ovarian Insufficiency SEMINARS IN REPRODUCTIVE MEDICINE Baker, V. 2011; 29 (4): 362-372

Abstract

Primary ovarian insufficiency (POI) compromises a woman's chance of conceiving with her own oocytes. Although biomarkers such as serum follicle-stimulating hormone, serum antimüllerian hormone, and assessment of antral follicle count by transvaginal ultrasound can give some general idea about ovarian activity and perhaps fertility potential, no marker will definitively predict if and when childbearing will be possible for women with POI. No medical therapy has yet been definitively proven to improve ovarian function and fertility for women with overt POI. Fertility preservation, with cryopreservation of ovarian tissue, oocytes, or embryos, can be considered for some women with POI if oocytes are retrievable and current childbearing is not desired, with the caveat that data regarding long-term safety and efficacy are not available for women with POI. Options with a high chance of success are oocyte donation, embryo donation, and adoption. Child-free living may be a reasonable choice for some women. It is beneficial for women with POI to hear all life-plan and family-building options presented in a balanced manner.

View details for DOI 10.1055/s-0031-1280921

View details for Web of Science ID 000294138600010

View details for PubMedID 21969270
The time is now for a new approach to primary ovarian insufficiency FERTILITY AND STERILITY Cooper, A. R., Baker, V. L., Sterling, E. W., Ryan, M. E., Woodruff, T. K., Nelson, L. M. 2011; 95 (6): 1890-1897

Abstract

To articulate the need for a new approach to primary ovarian insufficiency. The condition, also known as premature menopause or premature ovarian failure, is defined by the presence of menopausal-level serum gonadotropins in association with irregular menses in adolescent girls or women younger than 40 years. It can be iatrogenic as related to cancer therapy or may arise spontaneously, either alone or as part of a host of ultrarare syndromes. In a large percentage of spontaneous cases no pathogenic mechanism can be identified.Literature review and consensus building at a multidisciplinary scientific workshop.There are major gaps in knowledge regarding the etiologic mechanisms, psychosocial effects, natural history, and medical and psychosocial management of primary ovarian insufficiency. An international research consortium and disease registry formed under the guidance of an umbrella organization would provide a pathway to comprehensively increase basic and clinical knowledge about the condition. Such a consortium and patient registry also would provide clinical samples and clinical data with a goal toward defining the specific pathogenic mechanisms. An international collaborative approach that combines the structure of a patient registry with the principles of integrative care and community-based participatory research is needed to advance the field of primary ovarian insufficiency.

View details for DOI 10.1016/j.fertnstert.2010.01.016

View details for Web of Science ID 000289620900007

View details for PubMedID 20188353
Age-specific serum anti-Mullerian hormone values for 17,120 women presenting to fertility centers within the United States FERTILITY AND STERILITY Seifer, D. B., Baker, V. L., Leader, B. 2011; 95 (2): 747-750

Abstract

To determine age-specific serum anti-Müllerian hormone (AMH) values for women presenting to U.S. fertility clinics.Retrospective study.Single clinical reference laboratory.A total of 17,120 women of reproductive age ranging from 24 to 50 years old.None.Determination of single-year median and mean AMH values with SDs.Single-year-specific median, mean, and SD values are summarized in Table 1. Both median and mean AMH values decreased steadily in a manner highly correlated with advancing age. The average yearly decrease in the median serum AMH value was 0.2 ng/mL/year through age 35 and then diminished to 0.1 ng/mL/year after age 35. The rate of decline in mean AMH values was 0.2 ng/mL/year through age 40 and then diminished to 0.1 ng/mL/year thereafter.Median and mean AMH levels decreased steadily with increasing age from 24 to 50 years of age. Such data may be of value to physicians and their patients who are considering reproductive options.

View details for DOI 10.1016/j.fertnstert.2010.10.011

View details for Web of Science ID 000286419000066

View details for PubMedID 21074758
Day 2 versus day 3 embryo transfer in poor responders: a prospective randomized trial FERTILITY AND STERILITY Shahine, L. K., Milki, A. A., Westphal, L. M., Baker, V. L., Behr, B., Lathi, R. B. 2011; 95 (1): 330-332

Abstract

Day 2 embryo transfer has been suggested as a method to improve pregnancy rates in poor responders compared with day 3 transfer. Our prospective randomized controlled trial does not show a difference in outcomes based on day of embryo transfer.

View details for DOI 10.1016/j.fertnstert.2010.06.093

View details for Web of Science ID 000285411600086

View details for PubMedID 20813357
Age-Related Success with Elective Single versus Double Blastocyst Transfer. ISRN obstetrics and gynecology Friedman, B. E., Davis, L. B., Lathi, R. B., Westphal, L. M., Baker, V. L., Milki, A. A. 2011; 2011: 656204-?

Abstract

Background. Although the optimal outcome of assisted reproductive technology (ART) is a healthy singleton pregnancy, the rate of twin gestation from ART in women over the age of 35 is persistently high. Methods/Findings. We compared clinical pregnancy rates (PRs), ongoing pregnancy/live birth rates, and multiple gestation rates (MGRs) in 108 women who chose elective single blastocyst transfer (eSBT) to 415 women who chose elective double blastocyst transfer (eDBT) at a hospital-based IVF center. There was no significant difference in PR between eSBT and eDBT (57.4% versus 50.2%, P = 0.47) nor between eSBT and eDBT within each age group: <35, 35-37, 38-40, and >40. The risk of multiple gestations, however, was greatly increased between eSBT and eDBT (1.6 versus 32.4%, P < 0.00005), and this difference did not vary across age groups. Conclusion(s). Women undergoing eDBT are at uniformly high risk of multiple gestation regardless of age. eSBT appears to significantly lower the risk of multiple gestation without compromising PR.

View details for DOI 10.5402/2011/656204

View details for PubMedID 22191047
Inter-laboratory validation of the measurement of follicle stimulating hormone (FSH) after various lengths of frozen storage REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY Scriver, J., Baker, V. L., Young, S. L., Behr, B., Pastore, L. M. 2010; 8

Abstract

Serum follicle stimulating hormone (FSH) levels are used clinically to evaluate infertility, pituitary and gonadal disorders. With increased frequency of research collaborations across institutions, it is essential that inter-laboratory validation is addressed.An inter-laboratory validation of three commercial FSH immunoassays was performed with human serum samples of varying frozen storage length (2 batches of 15 samples each) at -25 degree C. Percentage differences and Bland-Altman limits of agreement were calculated.The inter- and intra-laboratory consistency of FSH values with the same assay manufacturer was much higher after shorter-term storage (frozen for less than 11 months, mean percentage degradation less than 4%) than after long-term storage (2-3 years, mean percentage degradation = 23%). Comparing assay results from different manufacturers, there was similar overall long term degradation as seen with the same manufacturer (-25%), however the degradation was greater when the original FSH was greater than 20 mIU/mL relative to less than 10 mIU/mL (p < 0.001 trend test).The findings suggest that degradation of serum samples stored between 11 months and 2-3 years at -25 degrees C can lead to unstable FSH measurements. Inter-laboratory variability due to frozen storage time and manufacturer differences in assay results should be accounted for when designing and implementing research or clinical quality control activities involving serum FSH at multiple study sites.

View details for DOI 10.1186/1477-7827-8-145

View details for Web of Science ID 000285635900001

View details for PubMedID 21114859
The impact on ovarian reserve after laparoscopic ovarian cystectomy versus three-stage management in patients with endometriomas: a prospective randomized study FERTILITY AND STERILITY Lewis, M., Baker, V., Nezhat, C. 2010; 94 (6): E81-E82

View details for DOI 10.1016/j.fertnstert.2010.08.010

View details for Web of Science ID 000283441400003

View details for PubMedID 20850721
Multivariate analysis of factors affecting probability of pregnancy and live birth with in vitro fertilization: an analysis of the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System FERTILITY AND STERILITY Baker, V. L., Luke, B., Brown, M. B., Alvero, R., Frattarelli, J. L., Usadi, R., Grainger, D. A., Armstrong, A. Y. 2010; 94 (4): 1410-1416

Abstract

To evaluate factors predictive of clinical pregnancy and of pregnancy loss from assisted reproductive technology (ART) using data from the Society for Assisted Reproductive Technology database for 2004-2006.Retrospective cohort.Clinic-based data.The study population included 225,889 fresh embryo transfer cycles using autologous oocytes and partner semen.None.Clinical intrauterine gestation (presence of gestational sac) and live birth (>or=22 weeks gestation and >or=300 g birth weight).Increasing maternal age was significantly associated with a reduced odds of conception and increased fetal loss until 19 weeks gestation, but not with later pregnancy loss. Intracytoplasmic sperm injection (ICSI), assisted hatching, and increasing number of embryos transferred had significant positive effects on the odds of conception and pregnancy continuation through the first trimester, but did not affect the risk of later loss. Blacks, Asians, and Hispanics had significantly lower odds of clinical pregnancy compared with whites. Also compared with whites, Hispanics and Asians had a significantly greater risk of pregnancy loss in the second and third trimesters, and blacks had a significantly greater risk of pregnancy loss in all trimesters.Certain demographic and ART treatment parameters influenced chance of conception and early pregnancy loss, whereas black race and Hispanic ethnicity were also significantly associated with late pregnancy loss in ART-conceived pregnancies.

View details for DOI 10.1016/j.fertnstert.2009.07.986

View details for Web of Science ID 000281674600041

View details for PubMedID 19740463
Factors affecting success rates in two concurrent clinical IVF trials: an examination of potential explanations for the difference in pregnancy rates between the United States and Europe FERTILITY AND STERILITY Baker, V. L., Jones, C. E., Cometti, B., Hoehler, F., Salle, B., Urbancsek, J., Soules, M. R. 2010; 94 (4): 1287-1291

Abstract

To compare a US clinical trial of gonadotropin therapy for IVF with a similar European trial to determine what factors may explain the higher clinical pregnancy rate in the US trial.Comparison of baseline, treatment, and outcome variables in the United States (US) and European trials.IVF practices in the US (n=4) and Europe (n=6).297 women undergoing IVF.None.Clinical pregnancy rate.Clinical pregnancy rates were 43.4% in the US compared with 29.7% in Europe (p=0.016), with a live birth rate of 38.2% versus 27.6% (p=0.064). This difference in clinical pregnancy rate could not be explained by differences in the US versus Europe for number of embryos transferred (2.3 vs. 2.6) or female age (34.6 vs. 30.4). Although the starting dose of gonadotropin was higher in the US trial compared with the European trial (300 versus 225 IU), the total dose of gonadotropin was only slightly higher in the US. In multiple logistic regression analysis of 81 pretransfer variables on clinical pregnancy, the only two found to be significant predictors of outcome were baseline endometrial thickness following down-regulation and number of days of gonadotropin treatment.This study suggests the possibility that US pregnancy rates may be higher in part because of differences in down-regulation or gonadotropin dosing. Other factors not assessed in these studies or in national datasets likely also contribute to the difference in pregnancy rates.

View details for DOI 10.1016/j.fertnstert.2009.07.1673

View details for Web of Science ID 000281674600021

View details for PubMedID 19815197
A cost-benefit analysis of preimplantation genetic diagnosis for carrier couples of cystic fibrosis FERTILITY AND STERILITY Davis, L. B., Champion, S. J., Fair, S. O., Baker, V. L., Garber, A. M. 2010; 93 (6): 1793-1804

Abstract

To perform a cost-benefit analysis of preimplantation genetic diagnosis (PGD) for carrier couples of cystic fibrosis (CF) compared with the alternative of natural conception (NC) followed by prenatal testing and termination of affected pregnancies.Cost-benefit analysis using a decision analytic model.Outpatient reproductive health practices.A simulated cohort of 1,000 female patients.We calculated the net benefit of giving birth to a child as the present value of lifetime earnings minus lifetime medical costs.Net benefits in dollars.When used for women younger than 35 years of age, the net benefit of PGD over NC was $182,000 ($715,000 vs. $532,000, respectively). For women aged 35-40 years, the net benefit of PGD over NC was $114,000 ($634,000 vs. $520,000, respectively). For women older than 40 years, however, the net benefit of PGD over NC was -$148,000 ($302,000 vs. $450,000, respectively).Preimplantation genetic diagnosis provides net economic benefits when used by carrier couples of CF. Although there is an upper limit of maternal age at which economic benefit can be demonstrated, carrier couples of CF should be offered PGD for prevention of an affected child.

View details for DOI 10.1016/j.fertnstert.2008.12.053

View details for Web of Science ID 000276678100010

View details for PubMedID 19439290
The sex ratio of singleton offspring in assisted-conception pregnancies 63rd Annual Meeting of the American-Society-for-Reproductive-Medicine Luke, B., Brown, M. B., Grainger, D. A., Baker, V. L., Ginsburg, E., Stern, J. E. ELSEVIER SCIENCE INC. 2009: 1579–85

Abstract

To evaluate the effect of intracytoplasmic sperm injection (ICSI) and male factor infertility on the sex ratio in births from assisted reproductive technology.Historic cohort study.Clinic-based data.The study population included 15,164 singleton live births in the Society for Assisted Reproductive Technology national database for 2005 from cycles using ejaculated sperm, categorized by the use of insemination or ICSI and the absence or presence of male factor infertility, and cleavage- versus blastocyst-stage embryo transfers (ETs).None.The probability of a male infant with and without the use of ICSI and in the presence or absence of male factor infertility.The sex ratio for all U.S. live births in 2005 was 52.5%, versus 48.9% for cleavage-stage and 51.6% for blastocyst-stage embryos. With blastocyst-stage embryos, the sex ratios were 49.6% and 54.9% with and without ICSI and 52.6% and 50.0% with and without male factor infertility, respectively. With cleavage-stage embryos, the sex ratio was not significantly affected by ICSI or male factor infertility, singly or in combination.The use of ICSI, particularly with blastocyst-stage embryos, is associated with a decrease in the sex ratio of male infants.

View details for DOI 10.1016/j.fertnstert.2008.08.107

View details for Web of Science ID 000271710200015

View details for PubMedID 18950756
Oocyte retrieval versus conversion to intrauterine insemination in patients with poor response to gonadotropin therapy FERTILITY AND STERILITY Shahine, L. K., Lathi, R. B., Baker, V. L. 2009; 92 (4): 1315-1317

Abstract

We compared cycle characteristics and outcomes for planned in vitro fertilization cycles with five or fewer developing follicles that proceeded to retrieval (n = 170) with those that converted to intrauterine insemination (IUI) (n = 50). The risk of no embryo transfer was 24% in cycles that proceeded to retrieval. Live birth rate per cycle started was similar for IUI (6%) compared with retrieval (7%).

View details for DOI 10.1016/j.fertnstert.2009.03.059

View details for Web of Science ID 000270616100028

View details for PubMedID 19393998
Instructing an Embryonic Stem Cell-Derived Oocyte Fate: Lessons from Endogenous Oogenesis ENDOCRINE REVIEWS Nicholas, C. R., Chavez, S. L., Baker, V. L., Pera, R. A. 2009; 30 (3): 264-283

Abstract

Female reproductive potential is limited in the majority of species due to oocyte depletion. Because functional human oocytes are restricted in number and accessibility, a robust system to differentiate oocytes from stem cells would enable a thorough investigation of the genetic, epigenetic, and environmental factors affecting human oocyte development. Also, the differentiation of functional oocytes from stem cells may permit the success of human somatic cell nuclear transfer for reprogramming studies and for the production of patient-specific embryonic stem cells (ESCs). Thus, ESC-derived oocytes could ultimately help to restore fertility in women. Here, we review endogenous and ESC-derived oocyte development, and we discuss the potential and challenges for differentiating functional oocytes from ESCs.

View details for DOI 10.1210/er.2008-0034

View details for Web of Science ID 000265979000006

View details for PubMedID 19366753
Clinical efficacy of highly purified urinary FSH versus recombinant FSH in volunteers undergoing controlled ovarian stimulation for in vitro fertilization: a randomized, multicenter, investigator-blind trial FERTILITY AND STERILITY Baker, V. L., Fujimoto, V. Y., Kettel, L. M., Adamson, G. D., Hoehler, F., Jones, C. E., Soules, M. R. 2009; 91 (4): 1005-1011

Abstract

To compare the efficacy of highly purified human urinary follicle stimulating hormone (HP-hFSH) versus human recombinant follitropin-alpha (rFSH) in volunteers undergoing controlled ovarian stimulation for IVF.A randomized, controlled, investigator-blind trial.Four assisted reproductive technology centers.One hundred fifty-two IVF patients.Volunteers, aged 18-39, were randomized to HP-hFSH (n = 76) versus rFSH (n = 76) at a starting dose of 300 IU in down-regulated cycles.Number of oocytes, clinical pregnancy rate, and live birth rate with HP-hFSH versus rFSH.The total IU of gonadotropin used did not differ between the two groups. There was no difference in number of oocytes retrieved with HP-hFSH (mean = 16.3) compared with rFSH (mean = 17.1), confidence interval (CI) of difference = -3.79 to +2.18. Clinical pregnancy rate, as defined by the presence of a gestational sac, was 48.7% (CI = 37.0%-60.4%) with HP-hFSH versus 44.7% (CI = 33.3%-56.6%) with rFSH (CI of difference = -11.9% to +19.8%). Live birth rate was 38.2% (29 of 76) in both groups (CI = 27.2%-50.0%), for a difference between groups of 0.0% (CI of the difference = -15.4% to +15.4%).There were no statistically significant differences in mean oocyte number, clinical pregnancy rate, or live birth rate between HP-hFSH versus rFSH.

View details for DOI 10.1016/j.fertnstert.2008.01.064

View details for Web of Science ID 000265132300007

View details for PubMedID 18367182
Balancing the professional and personal FERTILITY AND STERILITY Armstrong, A. Y., Alvero, R. J., Dunlow, S., Nace, M. C., Baker, V., Stewart, E. A. 2009; 91 (1): 18-21

Abstract

To review the common roles that physicians pursue away from work and identify related challenges and potential solutions, so that individuals can develop a personalized plan for success in each of the areas.Literature review.University-based and university-affiliated medical centers.No subjects were involved in this literature review.Literature searches in Entrez PubMed and the following Websites: http://www.apgo.org, http://www.psychiatrictimes.com, as well as other data sources.Results of physician surveys and summaries of strategies for achieving work-personal life balance.According to surveys of physicians in various specialties, a majority of physicians have high levels of job, marital, and parental satisfaction. However, professional and personal challenges faced by physicians include struggle with time management, lack of mentorship, and difficulty maintaining intimate relationships. Multiple potentially effective strategies have been described in the literature, including exerting control over hours worked, taking a long view of life that acknowledges the need for changing priorities over time, developing communication skills, seeking counseling services if needed that focus on physician relationships, and simplifying home life whenever possible.Although there are unique challenges in being a physician, partner, and parent, many of the professional challenges faced by physicians are common to many adults in the United States. Self-assessment may help individuals to clarify priorities and develop strategies that can lead to improved personal satisfaction.

View details for DOI 10.1016/j.fertnstert.2007.10.064

View details for Web of Science ID 000262396700002

View details for PubMedID 18191125
Genetic evaluation of oocyte donors: recipient couple preferences and outcome of testing FERTILITY AND STERILITY Baker, V. L., Rone, H. M., Adamson, G. D. 2008; 90 (6): 2091-2098

Abstract

To report preferences of recipient couples for genetic testing of their oocyte donors.Observational report of results from a genetic testing-options form implemented as part of routine care.Private practice.Recipients and oocyte donors.Recipient couples completed a form before screening of their oocyte donor that outlined required screening and recommended tests that the couple could accept or decline. Couples were given information about carrier frequency, risk to their child if results were abnormal, and cost.Percentage of couples accepting optional testing.Of the 63 couples with data available from their first testing-options form, 42 (67%) accepted and 21 (33%) declined fragile X testing, whereas 34 (54%) accepted and 29 (46%) declined karyotyping. When asked whether they would accept additional testing of their donor if it was recommended by a genetic counselor, 15 (24%) said that they would accept additional testing regardless of cost, 35 (56%) declined, and 13 (20%) indicated that their decision would depend on the cost. In many cases, history was elicited by the genetic counselor or test results were obtained that influenced further testing, decisions to proceed, or provided information important for the child.Recipient couples sometimes chose to decline tests that we recommended but did not require, despite the relatively low cost of this testing compared with the total cost of the oocyte donation cycle.

View details for DOI 10.1016/j.fertnstert.2007.10.069

View details for Web of Science ID 000261566800008

View details for PubMedID 18249390
Economic cost for implementation of the US Food and Drug Administration's Code of Federal Regulations Title 21, Part 1271 in an egg donor program FERTILITY AND STERILITY Baker, V. L., Gvakharia, M. O., Rone, H. M., Manalad, J. R., Adamson, D. 2008; 90 (3): 537-545

Abstract

To assess the economic cost of implementing the U.S. Food and Drug Administration's Code of Federal Regulations Title 21, Part 1271 for infectious screening of egg donors in our practice during the first year.Physicians and employees of our practice were surveyed to ascertain the scope of duties and the number of hours spent to implement the regulations. The economic cost to the practice and the cost of additional laboratories were calculated.Private practice.Egg donors and recipient couples who underwent treatment in our center from May 25, 2005 (the day regulations became effective) to May 25, 2006; and physicians, administrators, and staff who were employed by the practice during this time frame.Using a questionnaire, structured interviews were conducted for all physicians and employees of our practice. The information regarding number of hours was provided to our chief financial officer, who calculated the cost to the practice. The cost that recipient couples paid for laboratory tests that would not otherwise be required to meet American Society for Reproductive Medicine guidelines and the cost of an external audit were also added to the overall practice costs to determine a total cost associated with the regulations in the first year.List of activities associated with implementation of the regulations, personnel hours involved to implement the regulations, and economic cost to the practice and to recipient couples.The total number of personnel hours spent by our practice in preparation for implementation of the regulations was 623.3 hours. In the first year, 675.2 additional hours were required to implement the regulations for 40 donors who cycled during this time. The economic cost to the practice for both preparation and implementation of the regulations was $219, 838, and the cost of additional laboratory work borne by the recipient couples was $15,880. Thus, the total cost was calculated to be $235,718 at 1 year after implementation of the regulations.Implementation of the FDA 21 CFR, Part 1271 was associated with a very high economic cost, even if the costs incurred by the government to develop and implement the regulation are excluded.

View details for DOI 10.1016/j.fertnstert.2007.06.100

View details for Web of Science ID 000259317200011

View details for PubMedID 17953961
Use of progesterone in three challenging cases. Sexuality, Reproduction, and Menopause Carson S, Baker VL, Liu J, Wysocki S 2008: S30-36
A new SERM on the horizon. Female Patient Baker VL 2008; 33: 15-19
Correlation of thyroid stimulating hormone (TSH) level with pregnancy outcome in women undergoing in vitro fertilization 72nd Annual Meeting of the Pacific-Coast-Obstetrical-and-Gynecological-Society Baker, V. L., Rone, H. M., Pasta, D. J., Nelson, H. P., Gvakharia, M., Adamson, G. D. MOSBY-ELSEVIER. 2006: 1668–74

Abstract

The aim of this study was to determine if pregnancy outcome for women undergoing in vitro fertilization is correlated with pre-conception thyroid-stimulating hormone level.We performed a retrospective cohort study of in vitro fertilization cycles in our private practice with an initial positive serum human chorionic gonadotropin level and thyroid-stimulating hormone level available (n = 364). We examined whether or not birth outcome differed between cycles in which the thyroid-stimulating hormone was > 2.5 mIU/L compared with cycles with a thyroid-stimulating hormone level of < or = 2.5 mIU/L. Logistic regression was used to determine the association between thyroid-stimulating hormone level and spontaneous abortion rate.Delivery outcome was available for 195 cycles, 36% of which had a thyroid-stimulating hormone level > 2.5. The gestational age at delivery was higher in cycles with a thyroid-stimulating hormone < or = 2.5 than for cycles with a thyroid-stimulating hormone > 2.5 (38.5 vs 38.0 weeks for singletons, 36.0 vs 34.6 weeks for twins, overall P = .012 for thyroid-stimulating hormone level). The mean birth weight for cycles with a thyroid-stimulating hormone < or = 2.5 was higher than for cycles with a thyroid-stimulating hormone > 2.5 (7.33 vs 6.78 lbs for singletons, P = .024 and 5.36 vs 4.83 lbs for twins, P = .023). Restricting analysis to cycles where the woman was not taking thyroid replacement did not change the overall conclusions. There was a trend toward increasing risk of miscarriage with increasing thyroid-stimulating hormone level in nondonor cycles, controlling for age and day 3 follicle-stimulating hormone level, but this trend did not reach statistical significance.A pre-conception thyroid-stimulating hormone level > 2.5 mIU/L is associated with a lower gestational age at delivery and lower birth weight in women undergoing in vitro fertilization.

View details for DOI 10.1016/j.ajog.2006.03.040

View details for Web of Science ID 000238055100039

View details for PubMedID 16731084
Multiple births from assisted reproductive technologies: a challenge that must be met FERTILITY AND STERILITY Adamson, D., Baker, V. 2004; 81 (3): 517-522

Abstract

The success of assisted reproductive technologies (ART) has been accompanied by dramatic increases in multiple births and their associated costs. Physicians who perform ART must develop effective treatment paradigms to reduce multiple births or risk regulatory intervention.

View details for DOI 10.1016/j.fertnstert.2003.09.041

View details for Web of Science ID 000220180300008

View details for PubMedID 15037394
Subfertility: causes, treatment and outcome BEST PRACTICE & RESEARCH IN CLINICAL OBSTETRICS & GYNAECOLOGY Adamson, G. D., Baker, V. L. 2003; 17 (2): 169-185

Abstract

Common causes of subfertility include ovulatory disorders, tubal disease, peritoneal adhesions, endometriosis, uterine abnormalities, abnormalities of sperm and advancing female age. Infertility is unexplained after thorough evaluation in about 5-10% of cases. Significant caveats must be attached to the interpretation of available data regarding infertility treatments. Successful ovulation induction in anovulatory women is possible for nearly all women except in cases of ovarian failure. Surgery is an option for some patients with tubal damage, adhesions, endometriosis and uterine abnormalities. Male factor infertility may be amenable to treatment of a specific cause, but is often empirical with the use of intra-uterine insemination (IUI) or in vitro fertilization (IVF). Egg donation is currently the most effective treatment available for age-related infertility when other treatments have not been successful. Couples with unexplained infertility may be effectively treated with ovulation induction plus IUI or IVF.

View details for DOI 10.1053/ybeog.2003.358

View details for Web of Science ID 000183225600002

View details for PubMedID 12758094
Selective estrogen receptor modulators in reproductive medicine and biology OBSTETRICAL & GYNECOLOGICAL SURVEY Baker, V. L., Leitman, D., Jaffe, R. B. 2000; 55 (7): S21-S47

Abstract

Estrogen replacement therapy has significant potential benefits for postmenopausal women, such as improvement of menopausal symptoms and protection from osteoporosis, but it may also increase a woman's risk of breast cancer. Also, some women do not take hormone replacement therapy because of such undesirable side effects as breast tenderness and uterine bleeding. Therefore, there is much interest in the development of compounds that provide the benefits of estrogen replacement therapy without the risks and side effects. The selective estrogen receptor modulators make up one class of compounds with both estrogen agonist and antagonist activity. This review discusses the clinical indications, risks, benefits, and mechanisms of action of selective estrogen receptor modulators and related compounds.

View details for Web of Science ID 000166318500001

View details for PubMedID 10890575
Downregulation of protein kinase C by phorbol ester increases expression of epidermal growth factor receptors in transformed trophoblasts and amplifies human chorionic gonadotropin production PLACENTA Baker, V. L., Murai, J. T., Taylor, R. N. 1998; 19 (7): 475-482

Abstract

Epidermal growth factor (EGF) and its homologue, transforming growth factor-alpha (TGF-alpha), regulate human chorionic gonadotropin (hCG) synthesis in the human placenta. The current study was designed to investigate the involvement of the protein kinase C pathway in EGF-mediated hCG-beta production by JAr choriocarcinoma cells. Downregulation of protein kinase C activity by chronic exposure to the phorbol ester, phorbol 12,13-dibutyrate (PDB), produced a greater increase in hCG-beta secretion than did activation of protein kinase C activity by short-term exposure to PDB. Pretreatment with the protein kinase C inhibitors calphostin and chelerythrine also resulted in enhanced basal and EGF-stimulated hCG-beta production. Individual concentrations (5 nM EGF and 500 nM PDB) that maximally stimulated hCG production, were additive in combination. The additive effect of PDB on EGF-induced hCG-beta secretion was mediated in part by increased JAr cell EGF-receptor concentrations detected by Western blot and Scatchard analyses. The results suggest that EGF and PDB stimulate hCG production in JAr cells by different but interactive mechanisms. It is speculated that downregulation of protein kinase C stimulates basal and EGF-mediated hCG-beta production by uninhibiting other signalling pathways that regulate hCG-beta secretion in trophoblasts.

View details for Web of Science ID 000076134300004

View details for PubMedID 9778120
Minimum intrauterine pressure required for uterine distention 25th Annual Meeting of the American-Association-of-Gynecologic-Laparoscopists Baker, V. L., Adamson, G. D. JOURNAL AMER ASSOC GYNECOLOGIC LAPAROSCOPISTS. 1998: 51–53

Abstract

Study Objective. To determine the minimum intrauterine pressure required to distend the uterine cavity during hysteroscopy using saline as a distending medium. Design. Nonrandomized, prospective study (Canadian Task Force classification II-2). Setting. Ambulatory surgery suites. Patients. Seven women from the practice of the principal investigator. Intervention. Hysteroscopy was performed and intrauterine perfusion pressure was measured. Measurements and Main Results. Intrauterine perfusion pressure required to separate the anterior and posterior uterine walls was measured using a Cobe CDX pressure transducer kit. The uterine cavity was distended when intrauterine perfusion pressure reached a median of 40 mm Hg (range 25-50 mm Hg). Conclusion. This preliminary study suggests that a liquid with the same viscosity as normal saline distends the uterine cavity at a pressure of approximately 40 mm Hg. This pressure is lower than that at which spillage from fallopian tubes occurs, suggesting that it may theoretically be possible to ablate the endometrial lining with heated liquid without spilling liquid into the peritoneal cavity. Further study with larger numbers of patients is required to verify this finding.

View details for Web of Science ID 000073163000010

View details for PubMedID 9454877
Reproductive endocrine and endometrial effects of raloxifene hydrochloride, a selective estrogen receptor modulator, in women with regular menstrual cycles JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Baker, V. L., Draper, M., Paul, S., Allerheiligen, S., Glant, M., Shifren, J., Jaffe, R. B. 1998; 83 (1): 6-13

Abstract

Previous studies of raloxifene conducted in animal models and postmenopausal women have demonstrated antiestrogenic action on the endometrium. The purpose of this first study of raloxifene in women with normal menstrual cycles was to determine its reproductive endocrine and endometrial effects. In part I, raloxifene (400 mg) was administered for 5 days in the follicular, periovulatory, or luteal phase of the menstrual cycle (n = 12). In part II, women were randomized to receive raloxifene (100 or 200 mg) for 28 days beginning on day 3 of the cycle (n = 19). All women ovulated in both parts of the study. Raloxifene did not alter the length of the menstrual cycle or the day of the LH surge. A 5-day course of raloxifene administered in any phase of the cycle elevated FSH area under the curve (AUC) for the entire cycle and estradiol AUC for the second half of the cycle compared with those in control cycles. In part II, raloxifene also appeared to increase the FSH AUC and estradiol AUC. Raloxifene decreased the number of gland mitoses in follicular phase endometrial biopsies. Subtle effects suggestive of gland-stromal dysynchrony were noted in a limited number of the secretory phase endometrial biopsies. This study has demonstrated that 1) raloxifene does not prevent ovulation in women with normal menstrual cycles; 2) ovarian estrogen production will continue, and in some cases increase, in response to raloxifene; and 3) antiestrogenic effects of raloxifene on the endometrium are subtle in the endocrine milieu of normal to high circulating estradiol concentrations.

View details for Web of Science ID 000071270600003

View details for PubMedID 9435408
Human umbilical vessels and cultured umbilical vein endothelial and smooth muscle cells lack detectable protein and mRNA encoding estrogen receptors JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION Baker, V. L., Chao, V. A., Murai, J. T., Zaloudek, C. J., Taylor, R. N. 1997; 4 (6): 316-324

Abstract

To identify and characterize estrogen receptors in human umbilical vascular tissues and in cultured cells derived from the human umbilical vein.Human umbilical vein endothelial (HUVE) and human umbilical vein smooth muscle (HUVSM) cells were isolated. Immunohistochemical, radioligand binding. Western immunoblotting, and reverse transcription-polymerase chain reaction (RT-PCR) methods were used to detect estrogen receptors in vascular tissues and in cells derived from the umbilical cord.Estrogen receptor protein was not detected in either umbilical vessel tissue or in isolated HUVE or HUVSM cells. Messenger RNAs for the classic estrogen receptor (alpha) and estrogen receptor beta isoforms also were undetectable by RT-PCR.These findings suggest that the effects of estradiol observed in this widely used vascular model are mediated by very low concentrations of receptors that evade standard methods of detection. Alternatively, this steroid may affect umbilical vascular cells through mechanisms that do not involve the classic genomic estrogen-receptor pathway.

View details for Web of Science ID A1997YJ29000009

View details for PubMedID 9408888
Transvaginal reduction of an interstitial heterotopic pregnancy with preservation of the intrauterine gestation 63rd Annual Meeting of the Pacific-Coast-Obstetrical-and-Gynecological-Society Baker, V. L., Givens, C. R., Cadieux, M. C. MOSBY-YEAR BOOK INC. 1997: 1384–85

Abstract

With use of transvaginal ultrasonographic guidance, cardiac activity in an interstitial heterotopic pregnancy at 7 weeks' gestation was terminated. The interstitial pregnancy resolved, and a healthy term infant was delivered. If an early diagnosis of an interstitial heterotopic pregnancy is made, selective reduction may allow preservation of the intrauterine gestation without surgery.

View details for Web of Science ID A1997XH73400106

View details for PubMedID 9215203
Clinical uses of antiestrogens. Obstetrical & gynecological survey Baker, V. L., Jaffe, R. B. 1996; 51 (1): 45-59

Abstract

An antiestrogen is a compound that blocks the action of estrogen. Most synthetic antiestrogens have agonistic or antagonistic activity depending on the tissue and the endogenous estrogen mileu. The triphenylethylene derivatives, clomiphene and tamoxifen, are the antiestrogens in greatest clinical use. Their biologic effects, clinical indications, and risks are reviewed. Novel antiestrogens which are beginning to be studied clinically include the benzothiophene derivative, raloxifene and the "pure" antiestrogens such as ICI 182,780. New clinical indications for existing compounds as well as the development of novel antiestrogens may lead to better treatment options for endocrine-dependent conditions.

View details for PubMedID 8657397
THRESHOLD INTRAUTERINE PERFUSION PRESSURES FOR INTRAPERITONEAL SPILL DURING HYDROTUBATION AND CORRELATION WITH TUBAL ADHESIVE DISEASE FERTILITY AND STERILITY Baker, V. L., Adamson, G. D. 1995; 64 (6): 1066-1069

Abstract

To determine the minimum intrauterine perfusion pressure that will produce spill from the fallopian tubes into the peritoneal cavity and to correlate this pressure with the extent of tubal adhesive disease.Hydrotubation was performed at laparoscopy and intrauterine perfusion pressure was measured. The extent of peritubal and fimbrial adhesions was graded at laparoscopy.Ambulatory surgery suites.Ten patients with infertility and/or pelvic pain were enrolled in the study. Data from nine patients were analyzed.Measurement of intrauterine perfusion pressures.The minimum pressure that produced spill of dye from each fallopian tube and the correlation between extent of external tubal pathology and this threshold pressure.The median threshold pressure at which dye spilled from at least one fallopian tube was 100 mm Hg, and no spill occurred at pressures < 70 mm Hg. The threshold pressure was correlated negatively with the extent of tubal disease.Fluid with the same viscosity as hydrotubation dye will not spill into the peritoneal cavity through normal fallopian tubes until the intrauterine perfusion pressure exceeds 70 mm Hg. The threshold pressure is higher when tubal adhesive disease that can be visualized by laparoscopy is present.

View details for Web of Science ID A1995TF35400004

View details for PubMedID 7589653
ALTERNATIVES TO ORAL ESTROGEN REPLACEMENT - TRANSDERMAL PATCHES, PERCUTANEOUS GELS, VAGINAL CREAMS AND RINGS, IMPLANTS, AND OTHER METHODS OF DELIVERY OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA Baker, V. L. 1994; 21 (2): 271-297

Abstract

Alternatives to oral estrogen replacement, including the transdermal patch, deliver estradiol in a constant manner, produce more physiologic estrone and estradiol levels than oral therapy, and avoid the first-pass effect on hepatic protein synthesis. Transdermal patches and estradiol implants have been demonstrated to produce favorable lipid profiles, prevent bone loss, relieve vasomotor symptoms, and improve urogenital atrophy. Vaginal estrogen is an effective treatment for vaginal atrophy. The advantages and disadvantages of each of the hormonal alternatives to oral estrogen replacement are discussed.

View details for Web of Science ID A1994NR24300005

View details for PubMedID 7936545
Surrogacy: one physician's view of the role of law. University of San Francisco law review. University of San Francisco. School of Law Baker, V. L. 1994; 28 (3): 603-612

View details for PubMedID 11655177

Valerie L. Baker, MD

Professor of Obstetrics and Gynecology (Reproductive Endocrinology and Infertility) at the Stanford University Medical Center

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