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Objective: To study cycle outcomes of women who choose to pursue oocyte cryopreservation, using published age-specific oocyte recommendations., Design: Retrospective cohort., Setting: Clinic., Patient(s): A total of 5,915 patients seeking planned oocyte cryopreservation, 3,504 ultimately underwent ovarian stimulation with oocyte retrieval and cryopreservation, 425 of this cohort subsequently thawed with intent to use embryo transfer., Exposure: Planned oocyte cryopreservation., Main Outcome Measure(s): Planned oocyte cryopreservation consultation, fertility preservation cycle(s) and ovarian stimulation outcomes., Result(s): A total of 5,915 women were seen in the initial consultation for planned fertility preservation (2012-2022). Ethnicity and the highest level of education were significant in predicting who would move forward with oocyte stimulation for fertility preservation. Women who reported working within the law and public policy and in the fields of health and medicine were statistically more likely to proceed with a cycle than those who listed other occupations. Of 3,504 women in the study cohort who underwent ovarian stimulation and egg retrieval, 1,331 (38.0%) achieved the age-based recommended number of oocytes to freeze. Only 57 (4.3%) of these women who met their age-based oocyte goal did so after their initial cryopreservation cycle. There was a significant association between ethnicity and number of cryopreservation cycles, specifically showing that Black or African American women were less likely to complete two or more cycles. Patients whose education background included graduate or professional degrees were more likely to have completed more than one cycle., Conclusion(s): Self-identified ethnicity was significantly associated with the odds of moving forward with oocyte stimulation for fertility preservation and egg retrieval after initial consultation with ethnic minorities significantly less likely to continue treatment. Of those who undergo egg freezing, most women pursue more than one stimulation and cryopreservation cycle, yet the majority never meet their recommended number to freeze., Competing Interests: Declaration of Interests D.B. has nothing to disclose. M.B. has nothing to disclose. A.C.C. has nothing to disclose. R.Y. has nothing to disclose. S.R. has nothing to disclose. K.D. reports consulting fees from BluDiagnostics and Medscape; honoraria from University of California, San Diego and Pacific Coast Reproductive Society; travel support from The American Society for Reproductive Medicine, The Society for Assisted Reproductive Technology and U.S. Fertility; data safety monitoring boards for Medscape, BluDiagnostics, Future Fertility, and LifeWhisperer; The Society for Reproductive Endocrinology and Infertility Research Chair, The Society for Assisted Reproductive Technology QA Chair, Medical Director; and Chief Research Officer, U.S. Fertility; stocks in U.S. Fertility (indirect) and Shady Grove Fertility; options in LifeWhisperer and Future Fertility. M.H. has nothing to disclose. A.D. has nothing to disclose. T.S. has nothing to disclose., (Published by Elsevier Inc.)

Importance: Understanding the potential risks associated with fertility treatments (FTs) can guide clinical decision and patient counseling., Objective: To investigate the validity of the association between the development of female-specific malignancies including ovarian, endometrial, breast, and cervical cancer after FT., Data Sources: A search of systematic reviews and meta-analyses was performed from inception to April 2022 within several databases: Cochrane Database of Systematic Reviews, EMBASE, Google Scholar, and PubMed., Study Selection and Synthesis: The inclusion criteria required the incidence of each cancer subgroup to be stated in both the defined treatment group (controlled ovarian stimulation and/or in vitro fertilization [IVF] or intracytoplasmic sperm injection) and the control group (no-FT, general population). From 3,129 identified publications, 11 meta-analytical reviews consisting of 188 studies were selected for synthesis., Main Outcome: The primary outcome of interest was incidence of each subgroup of cancer in the "FT" group compared with the "no-FT" group., Results: A statistically significant increase in incidence of ovarian (1,229/430,611 in FT group vs. 27,358/4,263,300 in no-FT group) cancer (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.00-1.45) and borderline ovarian tumors (117/414,729 in FT group vs. 934/2,626,324 in no-FT group) (OR, 1.87; 95% CI, 1.18-2.97) was observed. The incidence of ovarian cancer was higher with FT and IVF specifically (OR, 1.65; 95% CI, 1.07-2.54). For borderline ovarian tumors, the incidence was higher, not only with FT overall and IVF, but also according to the fertility drug regimen applied: clomiphene citrate (CC) only (OR, 1.99; 95% CI, 1.02-3.87), human menopausal gonadotropin only (OR, 3.46; 95% CI, 1.39-8.59), and CC and human menopausal gonadotropin combined (OR, 3.79; 95% CI, 1.47-9.77). When using the threshold for statistical significance, the meta-analyses relevant to ovarian cancers remained statistically significant (random-effects method). However, none of the examined associations could claim either strong or highly suggestive evidence., Conclusion and Relevance: An observed association between ovarian cancer (including borderline ovarian tumors) and FT has been demonstrated. The association between FT and female-specific malignancy remains a contentious topic because there have been contradictory outcomes among meta-analyses. This umbrella review interrogates existing systematic reviews and meta-analyses on this topic and concludes that a statistically significant increase in the incidence of ovarian cancer and borderline ovarian tumors is associated with FT. These findings have a significant clinical impact because it helps to inform and provide effective counseling for patients undergoing FT., Competing Interests: Declaration of Interests S.S. has nothing to disclose. J.F.B. has nothing to disclose. L.S.K. has nothing to disclose. N. Galazis has nothing to disclose. B.N.D. has nothing to disclose. K.J.G. has nothing to disclose. T.B.-M. has nothing to disclose. B.P.J. has nothing to disclose. N. Getreu has nothing to disclose. M.C. has nothing to disclose. A.M. has nothing to disclose. M.A.-M. has nothing to disclose. J.B.-N. has nothing to disclose. J.R.S. has nothing to disclose. J.Y. has nothing to disclose. D.T. has nothing to disclose. T.B. has nothing to disclose. S.G.-M. has nothing to disclose. J.Y.V. has nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the minimum follicular volume on the day of trigger that will correspond to a mature oocyte at egg retrieval by individualized follicular puncture and to calculate the mean follicular growth from ovulation induction to egg retrieval using SonoAVCfollicle., Design: A prospective observational study of 53 women undergoing in vitro fertilization, in which it was possible to identify unequivocally one or more follicles at trigger and egg retrieval using three-dimensional ultrasound., Setting: University-affiliated private in vitro fertilization center., Patients: The final sample included 206 follicles from 14 oocyte donors and 39 patients., Interventions: A three-dimensional ultrasound with SonoAVCfollicle was performed at trigger and egg retrieval. The same operator selected follicles that were identified easily on both scans and verified that they were apt to be aspirated individually. Follicles were punctured individually, recording the real aspirated volume and the maturity stage of the oocyte., Main Outcome Measures: The primary outcome was the relationship between follicular volume on the day of the trigger and the oocyte maturity stage. The secondary outcome was the rate of follicular growth from the day of trigger to the day of oocyte retrieval, as measured using SonoAVCfollicle., Results: On the day of trigger 206, follicles were selected. Of these, 5 could not be identified on the day of oocyte retrieval, probably because of follicular rupture (mean volume: 4 cm 3 , range: 2-7 cm 3 ), and in 48, an oocyte was not obtained. The relationship between follicular volume and oocyte maturity was studied in 153 follicles: 125 (82%) contained mature and 28 (18%) contained immature oocytes. Receiver operating characteristic curves showed an area under the curve value of 0.73 (95% confidence interval: 0.65-0.80). A follicular volume of >0.56 cm 3 is the cutoff point, with the highest Youden index having a sensitivity of 85% and a specificity of 64% to predict oocyte maturity. The mean follicular growth from trigger to egg retrieval was 26%-50% in 53% of cases., Conclusion: A follicular volume of >0.56 cm 3 at trigger is the cutoff point with the optimal balance between sensitivity and specificity for oocyte maturity. Follicles of >2-3 cm 3 may undergo spontaneous rupture before egg retrieval. Given these findings, we propose new volume-based criteria for trigger: 70% of follicles of >0.6 cm 3 and dominant follicles between 2 and 3 cm 3 . These findings need validation by randomized controlled trials., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study the contribution of ovulation induction and ovarian stimulation, in vitro fertilization (IVF), and unassisted conception to the increase in national plural births in the United States, a significant contributor to adverse maternal and infant health outcomes., Design: National and IVF-assisted plural birth data were derived from the Centers for Disease Control and Prevention's National Vital Statistics System (1967-2021, after introduction of Clomiphene Citrate in the United States) and the National Assisted Reproductive Technology Surveillance System (1997-2021), respectively., Setting: Not applicable., Patient(s): Not applicable., Intervention(s): Not applicable., Main Outcome Measure(s): In addition to IVF-assisted plural births, the contributions of unassisted conception to plural births among women aged <35 and ≥35 years were estimated using plural birth rates from 1949-1966 and a Bayesian logistic model with race and age as independent variables. The contribution of ovulation induction and ovarian stimulation was estimated as the difference between national plural births and IVF-assisted and unassisted counterparts., Result(s): From 1967-2021, the national twin birth rate increased 1.7-fold to a 2014 high (33.9/1,000 live births), then declined to 31.2/1,000 live births; the triplet and higher order birth rate increased 6.7-fold to a 1998 high (1.9/1,000 live births), then declined to 0.8/1,000 live births. In 2021, the contribution of unassisted conception among women aged <35 years to the national plural births was 56.1%, followed by ovulation induction and ovarian stimulation (19.5%), unassisted conception among women aged ≥35 years (16.8%), and IVF (7.6%). During 2009-2021, the contribution of ovulation induction and ovarian stimulation has remained stable, the contribution of unassisted conception among women aged <35 and ≥35 years has increased, and the contribution of IVF has decreased., Conclusion(s): Ovulation induction and ovarian stimulation are leading iatrogenic contributors to plural births. They are, therefore, targets for intervention to reduce the adverse maternal and infant health outcomes associated with plural births. Maternal age of ≥35 years is a significant contributor to the national plural birth increase., Competing Interests: Declaration of interest E.Y.A. has nothing to report. A.S.P. has nothing to report. P.A.G. has nothing to report. A.D.K. has nothing to report. Y.Z. has nothing to report. D.M.K. has nothing to report. R.G. has nothing to report., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the serum anti-Müllerian hormone (AMH) concentrations in a large, well-phenotyped cohort of women with polycystic ovary syndrome (PCOS) and evaluate whether AMH predicts successful ovulation induction in women treated with clomiphene and metformin., Design: Secondary analysis of randomized controlled trial., Setting: Not applicable., Patient(s): A total of 333 women with anovulatory infertility attributed to PCOS who participated in the double-blind randomized trial entitled the Pregnancy in Polycystic Ovary Syndrome I (PPCOS I) study (registration number, NCT00068861) who had serum samples from baseline laboratory testing available for further serum analysis were studied., Intervention(s): Not applicable., Main Outcome Measure(s): The association between the baseline AMH levels in each of the 3 treatment groups and ovulation, pregnancy, and live birth rates were assessed., Result(s): A total of 322 individuals had a baseline AMH concentration available, of which the mean AMH was 11.7 ± 8.3 ng/mL (range 0.1-43.0 ng/mL). With each unit (1 ng/mL) increase in baseline AMH, the odds of ovulation decreased by 10% (odds ratio, 0.90; 95% confidence interval, 0.86-0.93); this effect did not differ by treatment group. Women with a high baseline AMH concentration (>8 ng/mL) were significantly less likely to ovulate compared with those with a normal baseline AMH concentration (<4 ng/mL) (odds ratio, 0.23; 95% confidence interval, 0.05-0.68). This remained statistically significant when controlling for confounders, including age, body mass index, time in study, and Homeostatic Model Assessment for Insulin Resistance score. Ovulation occurred even at very high AMH concentrations; there was no maximum level noted at which no ovulation events occurred. Baseline AMH concentration was not associated with pregnancy or live birth rates when controlling for confounders., Conclusion(s): These AMH values in well-phenotyped individuals with PCOS add to the literature and will aid in identifying AMH criteria for the diagnosis of PCOS. In women with infertility and PCOS, a higher AMH concentration was associated with reduced odds of ovulation with ovulation induction with clomiphene, clomiphene + metformin, and metformin., Clinical Trial Registration Number: The original trial from which this analysis is derived was entitled "Pregnancy in Polycystic Ovary Syndrome: A 30 Week Double-Blind Randomized Trial of Clomiphene Citrate, Metformin XR, and Combined Clomiphene Citrate/Metformin XR For the Treatment of Infertility in Women With Polycystic Ovary Syndrome" and was registered on ClinicalTrials.gov as number NCT00068861. The URL for the trial is https://clinicaltrials.gov/study/NCT00068861. The first subject was enrolled in November 2002., Competing Interests: Declaration of Interests A.S.K. reports that Ansh Labs provided funding for AMH/LH assays and Northwestern University Department of OB/GYN Biostatistical Support Grant and the Ralph Kazer Reproductive Endocrinology Fellowship Fund provided funding for statistical analyses and sample shipments for the submitted work. L.H. has nothing to disclose. P.S. has nothing to disclose. D.A.A. has nothing to disclose. A.K. has nothing to disclose. B.K. has nothing to disclose. R.S.L. reports funding from UL1 TR002014 National Center for Advancing Translational Sciences, 5 R01AT009484-02 Inositol Supplementation to Treat Polycystic Ovary Syndrome: A Double-Blind Dose Ranging RCT (INSUPP-P) NIH/NCCIH, 5 R01 HD091350-04 The COMET-PCOS Trial: Comparing the effects of Oral Contraceptive Pills vs. Metformin in the medical management of overweight/obese women with Polycystic Ovary Syndrome NIH/University of Pennsylvania, Guerbet USA Therapeutic Effect of Sonographic Hysterosalpingography: Oil vs. Water Based Media: The SHOW Pilot Trial, 5 R01 HD083323-04 Functional Analysis of PCOS Candidate Genes NIH/NICHD, 1 R01HD100630-01 AMH Signaling Pathway Variation in PCOS NIH, Hass Avocado Board A Multi-Site Randomized Clinical Trial to Compare Healthy Eating Recommendations for Six Months on Changes in Visceral Adiposity in Overweight/Obese Americans (Penn State Avocado Study), and 5 U10HD055925-10REV Data Coordinator Center for the RMN; consulting fees from Covis Pharma GmbH (2022), Novo Nordisk (12/2021), and Insudd (2020); honorarium from Honorary Professor, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China, 2012–present, Member, Steering Committee. Eastern Siberia PCOS Epidemiology & Phenotype study, Scientific Center of Family Health and Human Reproduction, Irkutsk, Russian Federation 2016–present, Member, International Advisory Panel, Developing, disseminating and implementing a core outcome set for infertility, funded by the Royal Society of New Zealand Catalyst Fund and the University of Auckland, New Zealand, 2017–present, Advisor, A metabolomic approach to redefine diagnostic criteria and classification of polycystic ovary syndrome (PI: Professor Chi Chui Wang, Chinese University of Hong Kong), funded by the Research Fund, Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (there are no in-person meetings.); PCOS Challenge (patient support group) Member, Medical/Scientific Advisory Board, 2017–present, Endocrine Society: Member Investment Subcommittee, 2018–present; Associate Editor, Human Reproduction Update, 2017-2020, Associate Editor, Fertility and Sterility, 2009-2020, Editorial Editor, Fertility and Sterility, 2020–present, Associate Editor, Global Reproductive Health, 2017–present; Owner of 1000 shares of Biodesix (BDSX); NIH, ZHD1 DSR-K (LR) 1 Loan Repayment Program (annually, 2008–present), Special Emphasis Panel/Scientific Review Group 10 ZHD1 DSR-M (55): National Centers for Translational Research in Reproduction and Infertility (2020), and Miscellaneous, Karolinska Institute, Stockholm, Sweden (2020) outside the submitted work. C.E.B. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the association between antimüllerian hormone (AMH) and preterm birth risk in a larger cohort of patients who underwent either in vitro fertilization or ovulation induction with intrauterine insemination at a US academic fertility center., Design: Retrospective cohort study., Setting: Single academic fertility center., Patient(s): Live singleton births from patients who underwent in vitro fertilization or ovulation induction between 2016 and 2020 at a single academic fertility center were included in this study. Patients were excluded if they had a missing prepregnancy AMH level, a pregnancy using donor oocytes or a gestational carrier, multiple gestations, a delivery before 20 weeks gestation, or a cerclage in place., Intervention(s): AMH level., Main Outcome Measure(s): The primary outcome was the proportion of preterm delivery. Secondary outcomes included the rate of pregnancy-induced hypertension, gestational diabetes, and small for gestational age., Result(s): In the entire cohort (n = 875), 8.4% of deliveries were preterm. The mean AMH values were similar between those with term and preterm births (3.9 vs. 4.2 ng/mL). Similar proportions of patients with term and preterm deliveries had AMH levels greater than the 75th percentile (25% vs. 21%). The odds of preterm birth were similar by AMH quartile after adjusting for the history of preterm birth. Similarly, in the polycystic ovary syndrome (PCOS) cohort, there was no difference between mean AMH values of term and preterm births (n = 139, 9.6 vs. 10.0 ng/mL). The proportions of patients with PCOS with AMH levels greater than the 75th percentile were similar between those with term and preterm deliveries (25% vs. 22%). The odds of preterm birth were similar by the AMH quartile after adjusting for the history of preterm birth., Conclusion(s): Elevated AMH levels were not associated with an increased risk of preterm birth in patients who conceived after in vitro fertilization and ovulation induction, including patients with PCOS. Although studies suggest that AMH levels may help stratify the risk of preterm birth in this population, our findings indicate that further studies are needed before clinical application., Competing Interests: Declaration of interests A.E.K. has nothing to disclose. M.K.S. has nothing to disclose. A.N. has nothing to disclose. N.K. has nothing to disclose. A.D. has nothing to disclose., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate if language preference influences intrauterine insemination outcomes., Design: Retrospective cohort., Setting: The study was conducted at an urban medical center in New York from January 2016 to August 2021., Patient(s): All women older than 18 years undergoing their first IUI cycle with an infertility diagnosis were included., Intervention(s): Intrauterine insemination after ovarian stimulation., Main Outcome Measure(s): Primary outcomes were intrauterine insemination success rate and duration of infertility before seeking infertility care. The primary outcomes used the Kaplan-Meier estimator to investigate the difference in duration of infertility before specialty consultation and logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) of clinical pregnancy among English speakers vs. those with limited English proficiency (LEP) undergoing initial IUI. Secondary outcomes included final IUI outcomes compared by language preference. Adjusted analyses controlled for race/ethnicity., Results: A total of 406 patients were included in this study, of which 86% preferred English, 7.6% preferred Spanish, and 5.2% preferred other. Patients with LEP have longer duration of infertility before seeking infertility care than English-proficient women (mean 4.53 ± 3.65 years vs. 2.01 ± 1.58 years). Although clinical pregnancy rate of initial IUI did not significantly vary (OR, 2.92; 95% CI, 0.68-12.47 unadjusted and OR, 2.88; 95% CI, 0.67-12.35 adjusted), the cumulative pregnancy rate was significantly higher in English-proficient patients than in LEP patients at the time of final IUI (22.32% vs. 15.38%). This is despite a similar number of total IUIs (2.40 English vs. 2.70 LEP). Additionally, LEP patients were significantly more likely to discontinue care after unsuccessful IUI, instead of proceeding to further fertility treatments such as in vitro fertilization., Conclusions: Limited English proficiency is associated with longer duration of infertility before initiating care as well as poorer IUI outcomes, including lower cumulative pregnancy rate. Further research is needed to assess what clinical and socioeconomic factors are contributing to lower IUI success rates and lower continuation in infertility care in LEP patients., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To describe a feasible fertility preservation strategy in a woman with vaginal carcinoma., Design: Video case report demonstrating the diagnostic work-up and laparoscopic oocyte retrieval performed under regional anesthesia., Setting: University tertiary care hospital., Patient(s): A 35-year-old nulliparous woman presented with vaginal bleeding and foul-smelling vaginal discharge. After a comprehensive diagnostic work-up, a final diagnosis of squamous cell carcinoma of the vagina stage II (Federation International Obstetrics and Gynecology classification) was made. As per the patient's desire, before undergoing chemoradiotherapy, the patient underwent oocyte cryopreservation. Transvaginal retrieval of oocytes was not feasible because of stenosis of the vaginal introitus and the potential risk of intracavitary tumor cell spillage. Transabdominal ultrasound-guided oocyte retrieval was not possible because of the body's habitus., Intervention(s): The patient underwent ovarian stimulation for in vitro fertilization. To minimize estrogen levels, letrozole was used during controlled ovarian stimulation. Laparoscopic oocyte retrieval was performed under spinal anesthesia., Main Outcome Measure(s): Successful laparoscopic egg retrieval and cryopreservation in a woman with squamous cell carcinoma of the vagina., Result(s): A total follicular count of nine was estimated before the oocyte retrieval. Eight oocytes were retrieved at laparoscopy, and eight mature oocytes were successfully cryopreserved. No complications were encountered, and the patient was discharged on the same day of surgery., Conclusion(s): To our knowledge, this is the first published case of fertility preservation using the laparoscopic approach in a patient with vaginal cancer. Letrozole is a valuable strategy to reduce high estrogen in patients with gynecological cancer undergoing controlled ovarian stimulation. Laparoscopy oocyte retrieval, performed under regional anesthesia, can be performed in an ambulatory setting and should be considered an effective fertility preservation strategy in patients with large vaginal tumors., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To evaluate the attachment rate of a human embryonic stem cell-derived trophoblastic spheroid onto endometrial epithelial cells in predicting the cumulative live birth rate of an in vitro fertilization (IVF) cycle., Design: A prospective observational study., Setting: University hospital and research laboratory., Patient(s): A total of 240 infertile women from 2017-2021., Intervention(s): Infertile women with regular cycles attending for IVF were recruited. An endometrial aspirate was collected from a natural cycle 1 month before IVF to determine the BAP-EB attachment rate., Main Outcome Measure(s): Cumulative live birth rates from a stimulated cycle and its derived frozen embryo transfer cycles within 6 months of ovarian stimulation were obtained., Result(s): The BAP-EB attachment rate in women who attained a cumulative live birth was similar to that in those who did not. When women were stratified by age into <35 years and ≥35 years, the BAP-EB attachment rate was significantly higher only in women aged ≥35 years having a live birth when compared with those in the same age group without a live birth. Receiver operating characteristic curve analysis of BAP-EB attachment rate in predicting cumulative live birth showed the areas under the curve of 0.559 (95% confidence interval [CI], 0.479-0.639), 0.448 (95% CI, 0.310-0.585), and 0.613 (95% CI, 0.517-0.710) for all ages, an age of <35 years, and an age of ≥35 years, respectively., Conclusion(s): The BAP-EB attachment rate offers only a very modest prediction of the cumulative live birth rate in women aged ≥35 years undergoing IVF., Clinical Trial Registration Number: NCT02713854 (https://clinicaltrials.gov/ct2/show/NCT02713854; Date of registration, March 21, 2016; date of enrollment of the first subject, August 1, 2017)., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Artificial intelligence has transformed many aspects of health care from image analysis to clinical decision making. Its evolution in medicine has been gradual and deliberate with several unanswered questions regarding efficiency, privacy, and bias. These artificial intelligence-based tools have relevance to assisted reproductive technologies with opportunities to impact informed consent, day-to-day management of ovarian stimulation, oocyte and embryo selection, and workflow. However, implementation must be an informed, cautious, and circumspect process to maximize outcomes and improve the clinical experience for patients and providers alike., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Because of the birth of the first baby after in vitro fertilization (IVF), the field of assisted reproductive technologies (ARTs) has seen significant advancements in the past 40 years. Over the last decade, the healthcare industry has increasingly adopted machine learning algorithms to improve patient care and operational efficiency. Artificial intelligence (AI) in ovarian stimulation is a burgeoning niche that is currently benefiting from increased research and investment from both the scientific and technology communities, leading to cutting-edge advancements with promise for rapid clinical integration. AI-assisted IVF is a rapidly growing area of research that can improve ovarian stimulation outcomes and efficiency by optimizing the dosage and timing of medications, streamlining the IVF process, and ultimately leading to increased standardization and better clinical outcomes. This review article aims to shed light on the latest breakthroughs in this area, discuss the role of validation and potential limitations of the technology, and examine the potential of these technologies to transform the field of assisted reproductive technologies. Integrating AI responsibly into IVF stimulation will result in higher-value clinical care with the goal of having a meaningful impact on enhancing access to more successful and efficient fertility treatments., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the association between the number of oocytes retrieved and the numbers of fertilized oocytes and blastocysts and cumulative and primary transfer live birth rates (LBRs)., Design: Retrospective study., Setting: Retrieval cycles and linked embryo transfers from the Society for Assisted Reproductive Technology Clinic Outcome Reporting System., Patient(s): Patients in the United States undergoing autologous in vitro fertilization cycles from 2014 to 2019 (n = 402,411 cycles)., Intervention(s): None., Main Outcome Measure(s): Normally fertilized oocytes, blastocysts, and cumulative and primary transfer LBRs., Result(s): There was a strong positive linear correlation between oocytes and fertilized oocytes and between oocytes and blastocysts. The cumulative LBR increased rapidly with the number of oocytes retrieved to approximately 16-20 oocytes, at which point it continued to increase but with diminishing returns. The increasing trend of the cumulative LBR was observed when stratifying patients by age and antimüllerian hormone and after controlling for confounding variables using multivariate logistic regression. The primary transfer LBR also increased with the number of oocytes to approximately 16-20 oocytes, at which point it plateaued but did not decline., Conclusion(s): A higher number of oocytes retrieved improves the cumulative LBR without impairing the primary transfer LBR. This suggests that ovarian stimulation strategies should aim to safely maximize the number of oocytes retrieved., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To identify whether the serum estradiol (E2) level on the day of human chorionic gonadotropin (hCG) trigger or luteinizing hormone (LH) surge (hCG-LH) was associated with the live birth rate (LBR) during ovulation induction (OI) or controlled ovarian hyperstimulation with letrozole followed by intrauterine insemination (IUI)., Design: Retrospective cohort study., Setting: Large, multicenter private practice., Patient(s): A total of 2,368 OI-IUI cycles in patients treated with letrozole followed by IUI were evaluated from January 1, 2014, to July 31, 2019., Intervention(s): Ovulation induction with letrozole, followed by autologous IUI., Main Outcome Measure(s): The primary outcome measure was the LBR as a function of the serum E2 level at the time of hCG administration or LH surge, adjusting for age, body mass index, the largest follicle diameter, and the number of follicles ≥14 mm in diameter. The clinical pregnancy rate as a function of the E2 level, pregnancy rate as a function of the lead follicle diameter, and pregnancy loss rates were the secondary outcome variables., Result(s): A total of 2,368 cycles met the inclusion criteria. Outcomes were evaluated at the 25th (E2 level, 110 pg/mL), 50th (157 pg/mL), 75th (225 pg/mL), and 90th (319 pg/mL) percentiles. The LBRs ranged from 9.4% to 11.1% in the lower E2 cohorts and from 12.5% to 13.5% in the higher E2 cohorts. The LBR was significantly greater in the cohort of women with higher E2 levels in all percentile comparisons except for the 90th percentile. The mean periovulatory follicle diameter of ≥20 or <20 mm was not independently associated with the LBR or clinical pregnancy rate, despite a significantly higher mean E2 level in the larger follicle group., Conclusion(s): In letrozole OI cycles followed by IUI, lower LBRs and clinical pregnancy rates were found in women with lower E2 levels than in those with higher E2 levels at the 25th, 50th, and 75th percentile E2 level quartiles. Where possible, delaying hCG trigger until the E2 level increases after aromatase inhibition and approaches the physiologic periovulatory level may improve the pregnancy rates with letrozole followed by IUI., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Oocyte in vitro maturation (IVM) is an assisted reproductive technology with a long and sometimes checked history. It is a minimally invasive technique involving the deliberate collection of immature oocytes from patients that have received no or minimal ovarian stimulation and the culture of oocytes to maturity in vitro, before standard procedures thereafter. Now, IVM is classified as nonexperimental and is primarily indicated for patients with a high antral follicle count, especially patients with polycystic ovaries or polycystic ovary syndrome, as well as for fertility preservation in cancer patients. In the recent past, IVM practice has had a confusing array of clinical protocols and has been slow to adapt to new scientific insights; however, recently, significant advances have been made in IVM culture methods based on new knowledge from animal studies, combined with defining a simple patient treatment protocol. These improvements have led to significant recent progress in IVM practice to the extent that IVM is now routinely practiced in a growing number of centers with specialized expertise around the world., (Copyright © 2023. Published by Elsevier Inc.)

In this review, we have summarized the evolution in our understanding of a relevance of gonadotropin dosing for cycle outcomes in women attempting to conceive through the utilization of the in vitro fertilization technology., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate whether extending letrozole (LE) treatment duration could induce ovulation in women with polycystic ovary syndrome (PCOS) who previously failed to ovulate after a 5-day regimen of 5 mg LE daily for at least 1 ovulation induction cycle, defined as "LE resistance"., Design: Retrospective cohort study., Setting: Tertiary care academic medical center., Patient(s): A total of 69 women with PCOS and LE resistance were included., Intervention(s): The duration of LE treatment was increased in a stepwise manner (named as "2-step extended LE regimen"): a 7-day regimen of 5 mg LE daily was prescribed in the first ovulation induction cycle, and if ovulation did not occur, a 10-day regimen was prescribed in the subsequent cycle., Main Outcome Measure(s): Ovulation rate was the primary outcome. Clinical pregnancy rate, live birth rate, spontaneous ovulation rate, and ovarian hyperstimulation syndrome rate were the secondary outcomes., Result(s): Of the 69 patients, 48 ovulated after the 7-day and 16 after the 10-day regimen. Overall, the cumulative ovulation rate reached 92.75% (64/69) after the 2-step extended LE regimen, with a cumulative clinical pregnancy rate of 31.88% (22/69) and a cumulative live birth rate of 24.63% (17/69). All patients ovulated spontaneously without exogenous trigger agents and none experienced ovarian hyperstimulation syndrome., Conclusion(s): Extending LE treatment duration is a feasible method for inducing ovulation in women with PCOS and LE resistance., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the ongoing pregnancy rate among patients with infertility with a low antimüllerian (AMH) level compared with those with a normal AMH level after oral and injectable ovulation induction (OI)/intrauterine insemination (IUI)., Design: Retrospective cohort., Setting: Academic center., Patient(s): Patients completing ≥1 medicated OI/IUI cycle at our center between 2015 and 2019 were included. The AMH levels were measured within 12 months of treatment initiation. The cohort was stratified into low AMH (AMH level, <1.0 ng/mL) and normal AMH (AMH level, ≥1.0 ng/mL) groups. All subsequent medicated OI/IUI cycles occurring within 1 year of initial cycle start date were included up to the third completed cycle or until an ongoing pregnancy was recorded. Patients were stratified by age (<35, 35-40, and >40 years), and the relationship between the low and normal AMH groups and each binary endpoint were quantified as risk ratios using the age-adjusted Poisson models., Intervention(s): None., Main Outcome Measure(s): Ongoing pregnancy., Result(s): A total of 3,122 patients completed 5,539 oral antiestrogen cycles, and 1,060 completed 1,630 injectable gonadotropin cycles. For oral antiestrogen treatment, pregnancy outcomes, including ongoing pregnancy rate per cycle, for patients with a low AMH level were comparable with those for patients with a normal AMH level (<35 years, 15.4% vs. 14.9%; 35-40 years, 10.0% vs. 11.0%; and >40 years, 2.8% vs. 3.3%). For injectable gonadotropin treatment, the ongoing pregnancy rate was lower in the low AMH group than in the normal AMH group for the ages of <35 (12.1% vs. 23.5%; relative risk [RR], 0.52 [95% confidence interval {CI}, 0.28-0.97]) and 35-40 (12.5% vs. 18.5%; RR, 0.70 [95% CI, 0.49-0.99]) years but comparable with that for patients aged >40 years (3.0% vs. 4.0%; RR, 0.86 [95% CI, 0.31-2.35]). The proportion of multifetal gestations was similar between the low and normal AMH groups treated with oral antiestrogens (13.1% vs. 10.8%); however, for injectable gonadotropin treatment, patients with a normal AMH level had a higher proportion of multifetal gestations (18.6% vs. 31.1%)., Conclusion(s): Compared with normal ovarian reserve, treatment with oral antiestrogens for OI/IUI for patients with low ovarian reserve results in comparable follicular development and ongoing pregnancy rates for all age groups. When patients with low ovarian reserve are treated with gonadotropins for OI/IUI, multifollicular recruitment is less likely resulting in a significantly decreased ongoing pregnancy rate for patients aged <35 and 35-40 years but also a decrease in multifetal gestations. Overall, the ongoing pregnancy rates of 8.7% per oral antiestrogen cycle and 8.1% per injectable gonadotropin cycle in patients with low ovarian reserve are comparable with the expected rates in the general infertility population., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To evaluate whether children conceived using assisted reproductive technology (ART) or ovulation induction (OI) have greater cardiometabolic risk than children conceived without treatment., Design: Clinical assessments in 2018-2019 in the Upstate KIDS cohort., Setting: Clinical sites in New York., Patient(s): Three hundred thirty-three singletons and 226 twins from 448 families., Intervention(s): Mothers reported their use of fertility treatment and its specific type at baseline and approximately 4 months after delivery. High validity of the self-reported use of ART was previously confirmed. The children were followed up from infancy through 8-10 years of age. A subgroup was invited to participate in clinic visits., Main Outcome Measure(s): The measurements of blood pressure (BP), arterial stiffness using pulse wave velocity, anthropometric measures, and body fat using bioelectrical impedance analysis were performed (n = 559). The levels of plasma lipids, C-reactive protein, and hemoglobin A1c were measured using blood samples obtained from 263 children., Result(s): The average age of the children was 9.4 years at the time of the clinic visits Approximately 39% were conceived using fertility treatment (18% using ART and 21% using OI). Singletons conceived using fertility treatment (any type or using ART or OI specifically) did not statistically differ in systolic or diastolic BP, heart rate, or pulse wave velocity. Singletons conceived using OI were smaller than singletons conceived without treatment, but the average body mass index of the latter was higher (z-score: 0.41 [SD, 1.24]) than the national norms. Twins conceived using either treatment had lower BP than twins conceived without treatment. However, twins conceived using OI had significantly higher arterial stiffness (0.59; 95% CI, 0.03-1.15 m/s), which was attenuated after accounting for maternal BP (0.29; 95% CI, -0.03 to 0.46 m/s). Twins did not significantly differ in size or fat measures across the groups. The mode of conception was not associated with the levels of lipids, C-reactive protein, or glycosylated hemoglobin., Conclusion(s): Clinical measures at the age of 9 years did not indicate greater cardiometabolic risk in children conceived using ART or OI compared with that in children conceived without treatment., Clinical Trial Registration Number: ClinicalTrials.gov #NCT03106493., (Published by Elsevier Inc.)

The assessments of oocyte quality and quantity and endocrine profile have traditionally been the cornerstone of the general workup of couples with infertility. Over the years, several clinical, hormonal, and functional biomarkers have been adopted to assess ovarian function and identify endocrine disorders before assisted reproductive technology. Furthermore, the genetic workup of patients has drastically changed, introducing novel markers. This not only allowed the prediction of response to ovarian stimulation but also contributed toward the development of a safer and more efficient management of women undergoing assisted reproductive technology. The scope of this review is to provide an overview of the current and novel strategies adopted for the assessment of ovarian function and ovulatory and endocrine disorders in women planning to conceive. Furthermore, it aims to provide an insight in the role of novel genetic biomarkers and use of expanded carrier screening as part of preliminary workup of women with infertility., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the influence of coronavirus disease 2019 (COVID-19) messenger ribonucleic acid vaccine on ovarian response and in vitro fertilization (IVF) treatment outcomes., Design: A retrospective cohort study., Setting: A tertiary university-affiliated medical center and a private medical center., Patient(s): The study included a total of 400 patients, 200 vaccinated women and 200 age-matched unvaccinated women, who underwent IVF in January-April 2021., Intervention(s): None., Main Outcome Measure(s): The mean number of oocytes retrieved and clinical pregnancy rates in vaccinated vs. unvaccinated patients., Result(s): A total of 200 patients underwent oocyte retrieval 14-68 days after receiving COVID-19 vaccination. No difference was found in the mean number of oocytes retrieved per cycle (10.63 vs. 10.72) between vaccinated and unvaccinated patients. Among 128 vaccinated and 133 unvaccinated patients who underwent fresh embryos transfers, no difference was demonstrated in the clinical pregnancy rates (32.8% vs. 33.1%), with 42 and 44 clinical pregnancies, respectively. The fertilization rates and mean number of cryopreserved embryos were similar between the 2 groups in freeze-all cycles (55.43% vs. 54.29% and 3.59 vs. 3.28, respectively). Among vaccinated and unvaccinated patients who underwent fresh embryo transfers, no difference was noted in the fertilization rate (64.81% vs. 61.98%) and transferred embryos' quality. Regression models applied demonstrated no effect of the vaccine on oocyte yields and pregnancy rates., Conclusion(s): The COVID-19 messenger ribonucleic acid vaccine did not affect the ovarian response or pregnancy rates in IVF treatment. Women should be vaccinated for COVID-19 before attempting to conceive via IVF treatments, given the higher risk of severe illness in pregnant women., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To study the effect of patients' immunization after coronavirus disease 2019 (COVID-19) infection or messenger ribonucleic acid (mRNA) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine on frozen-thawed embryo transfer (FET)., Design: Cohort retrospective study., Setting: Tertiary university affiliated medical center., Patient(s): All consecutive patients undergoing FET cycles in our center. The study group (immune group) consisted of patients treated during the COVID-19 pandemic (between January 2021 and August 2021) who either recovered from COVID-19 infection or received the mRNA SARS-CoV-2 vaccine. The control groups consisted of patients treated during the COVID-19 pandemic (between January 2021 and August 2021) but were not infected or did not receive the mRNA SARS-CoV-2 vaccine (not-immune2021 group) and those treated between January 2019 and August 2019 (before the pandemic) (not-immune2019 group)., Intervention(s): Frozen-thawed embryo transfer cycles., Main Outcome Measure(s): Ongoing pregnancy rates and FET cycles' characteristics. Data on patient age and variables related to infertility treatment were collected from the patient records., Result(s): During the study periods, 428 patients underwent 672 FET cycles. The immune group consisted of 141 patients who underwent 264 FET cycles (44 in postinfection and 220 in postvaccination), whereas the not-immune2021 and not-immune2019 groups consisted of 93 and 194 patients undergoing 125 and 283 FET cycles, respectively. Patients' characteristics and the types of endometrial preparations were comparable between the study groups. The implantation rate and clinical and ongoing pregnancy rates per transfer were similar between the study groups (immune group, postinfection and postvaccination; not-immune2021 group; not-immune2019 group)., Conclusion(s): Coronavirus disease 2019 infection or vaccination did not affect patients' performance or implantation in their subsequent FET cycle., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Growth hormone, letrozole, and clomiphene citrate do not have US Food and Drug Administration approval for their use in in vitro fertilization (IVF) cycles. However, despite this fact, they often are used to augment the IVF cycle in women considered "low responders." Unfortunately, because of the problems inherent to recruiting women who have undergone several unsuccessful IVF treatment cycles, and their inevitable low live birth rate, studies involving adjuvants for women considered low responders to ovarian stimulation often are underpowered. This is compounded further by the difficulty in recruiting vulnerable women to a study with a placebo arm. Consequently, the evidence base for their use as adjuncts to IVF treatment may be limited, and consequently their use may be empirical rather than evidence based. This short narrative review describes the evidence for these "add-ons" for a patient with a low response to ovarian stimulation. It suggests that a woman with a low ovarian response will derive benefit from using growth hormone; with a reduction in the ovarian stimulation required for oocyte retrieval, collection of a greater number of oocytes, and improvement in the clinical pregnancy rate. Although there currently is insufficient evidence to state categorically that it leads to an increased chance of a live birth. In the same situation, clomiphene citrate and letrozole lead to a reduced requirement for gonadotropins before oocyte retrieval, but with no improvement in live birth rate for their use., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This month's Views and Reviews provides insights into one of the most difficult clinical care populations: individuals with low ovarian reserve and limited response to stimulation. After a discussion of available definitions of "poor ovarian response" and how new definitions are improving the characterization of the individual patient and our ability to offer prognosis, we review alternative strategies for management. The first chapter presents options for pretreatment, including hormonal manipulation and nutriceuticals. The second chapter discusses the potential benefit of more gentle stimulation in this population. Subsequent chapters address adjuvants during stimulation, alterations of final oocyte maturation and processes in the laboratory, and finally when and how to stop treatment., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

This Committee Opinion provides practitioners with suggestions to reduce the likelihood of iatrogenic multiple gestation resulting from infertility treatment. This document replaces the document of the same name previously published in 2012 (Fertil Steril 2012;97:825-34 by the American Society for Reproductive Medicine)., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To estimate the probability of clinical or multiple pregnancy during ovulation induction (OI)/ovarian stimulation (OS)., Design: Secondary analysis of two multicenter randomized clinical trials (combined)., Setting: Multicenter., Patients: A total of 750 women with polycystic ovary syndrome and 900 women with unexplained infertility., Interventions: Ovulation induction/OS with either timed intercourse (polycystic ovary syndrome) or intrauterine insemination., Main Outcome Measures: Clinical and multiple pregnancy rates/cycle, cumulative pregnancy rates. Age, body mass index, parity, diagnosis, medication, markers of ovarian reserve, and ovarian response were considered in multivariable regression models for clinical, multiple, and cumulative pregnancy rates. Receiver operating characteristic curves were created for clinical and multiple pregnancy rates., Results: Younger patient and partner age, treatment type, lower body mass index, and medication dose were all associated with clinical pregnancy. Variables associated with multiple pregnancy included the abovementioned variables (except age), in addition to diagnosis, parity, higher antral follicle count, antimüllerian hormone levels, and ovarian response. Gonadotropin use was associated with multiple pregnancy, with progressively increasing odds ratios (cycles 1-4). Receiver operating characteristic curves indicated the model's predictive power to be fair for clinical pregnancy (areas under the curve [95% confidence interval {CI}]: 0.78 [0.75-0.81] for cycle 1 and 0.70 [0.64-0.75] for cycle 4) and good-to-excellent for multiple pregnancy (areas under the curve [95% CI]: 0.78 [0.72-0.84] for cycle 1 and 0.86 [0.78-0.93] for cycle 4). Partner age, lower medication dose, parity, antimüllerian hormone levels, and diagnosis were associated with cumulative pregnancy rates., Conclusions: Using the majority of the factors known to predict the outcome of OI/OS cycles, we constructed an easy-to-use formula that may predict individualized chances of clinical and multiple pregnancy for commonly used fertility treatments (https://pregnancyprediction.medicine.yale.edu/CalDirect.html)., Clinical Trial Registration Numbers: Assessing Multiple Intrauterine Gestations after Ovulation Stimulation NCT01044862; PPCOSII NCT00719186., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To compare neonatal and maternal outcomes among twin pregnancies conceived as a result of different types of fertility treatments with those of spontaneously conceived twin pregnancies., Design: Retrospective Cohort., Setting: Population-based analysis., Patient(s): Population-based analysis of twin pregnancies in the United States based on their mode of conception using the natality data from the National Center for Health Statistics from the Centers for Disease Control and Prevention (from January 2015 through December 2017)., Intervention(s): None., Main Outcome Measure(s): Adverse neonatal and maternal outcomes., Result(s): The overall prevalence of early adverse maternal outcomes and medical complications and obstetric complications including the risk of unplanned hysterectomy, intensive care unit admission, maternal blood transfusion, and perineal laceration were significantly higher in the fertility treatment group (including both ovulation induction/intrauterine insemination and assisted reproductive technology groups) compared with those of the spontaneous conception group, even after adjusting for several potential confounders. The risk of adverse composite neonatal outcomes was slightly lower in the spontaneous conception live twin birth group even after adjustment for several potential confounders., Conclusion(s): The rate of maternal and neonatal morbidity in twins conceived via different fertility treatments was slightly increased compared with those of twins conceived spontaneously. Because the absolute risks of maternal and neonatal morbidity were low, overall reassurance regarding these outcomes can be provided to the patients undergoing all types of fertility treatments., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the diagnostic performance of the antimüllerian hormone (AMH) level determined using the Access AMH assay for predicting poor ovarian response (POR) defined as ≤4 oocytes retrieved, including the validation of the predefined AMH cutoff of 0.93 ng/mL in both serum and plasma., Design: Prospective cohort study., Setting: Fifteen private and academic fertility centers (14 in the United States and 1 in Canada)., Patient(s): Women aged 21-45 years planning controlled ovarian stimulation for in vitro fertilization., Intervention(s): None., Main Outcome Measure(s): Number of oocytes retrieved, categorized as POR and normal-to-high ovarian response (non-POR). The correlation of AMH level and antral follicle count., Result(s): Data were available for 472 participants who completed the study (74 with POR and 398 non-POR). The mean AMH serum level among those with POR was 0.99 ng/mL (median 0.76 ng/mL) compared with 2.83 ng/mL (median 2.36 ng/mL) among the normal-to-high responders. For confirmation of the 0.93 ng/mL AMH level cutoff as a predictor of POR, a receiver operating characteristic analysis gave an area under the curve of 0.852, with corresponding sensitivity and specificity of 63.5% and 89.2%, respectively. The associated positive predictive value was 52.2% and the negative predictive value was 92.9%. The AMH plasma values demonstrated a strong correlation with AMH serum values with an r value = 0.9980. The previously established AMH cutoff of 1.77 ng/mL for antral follicle count >15 resulted in a sensitivity of 83.8% (95% confidence interval [CI] 77.7-88.5) and a specificity of 59.9% (95% CI 54.2-65.4)., Conclusion(s): This study validated the previously established AMH cut-point for the prediction of POR. Because this cut-point may vary depending on the assay used, the specific AMH assay should be reported in the literature whenever possible., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To determine the relationship between high antimüllerian hormone (AMH) levels and increased preterm delivery risk in populations of women with polycystic ovary syndrome (PCOS) or unexplained infertility undergoing ovulation induction., Design: Secondary analysis of data from two multicenter randomized clinical trials: Pregnancy in Polycystic Ovary Syndrome II (PPCOS II); and Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS)., Setting: Not applicable., Patients: Live births at ≥24 weeks' gestation from both the PPCOS II (n = 172) and AMIGOS (n = 222) cohorts were evaluated, and those at risk for iatrogenic preterm delivery including placental conditions, fetal growth restriction, multiple gestations, hypertensive diseases of pregnancy, and pre-gestational diabetes were excluded. The final analysis included 118 women with PCOS from the PPCOS II cohort and 146 women with unexplained infertility from the AMIGOS cohort., Intervention(s): None., Main Outcome Measure(s): Spontaneous preterm delivery., Results: In the PCOS population, median AMH overall was 5.5 ng/dL (interquartile range 2.9-9.3 ng/dL). In all, 62% of participants who delivered preterm had AMH levels above the 75th percentile. When comparing clinical covariates between the preterm and term deliveries, women with PCOS who delivered preterm had notably higher AMH than their term counterparts (11.1 vs. 5.4 ng/mL). In the univariate logistic regression analysis, each unit increase in AMH raised the odds of preterm delivery by 14% (odds ratio 1.14, 95% confidence interval 1.02-1.26). The effect was magnified only after adjusting for age, race, body mass index, smoking status, testosterone, homeostatic model assessment for insulin resistance, and treatment randomization group (adjusted odds ratio 1.25, 95% confidence interval 1.06-1.49). Unlike in the PCOS population, the unexplained infertility cohort had no significant difference in AMH levels between those with or without preterm delivery (2.3 vs. 2.6 ng/mL)., Conclusions: Our findings suggest that women with PCOS and high AMH who conceived after ovulation induction represent a high-risk group for preterm delivery. These data indicate that closer monitoring in the third trimester of pregnancies in PCOS patients with early first trimester AMH levels above 9.3 ng/mL may be warranted., Clinical Trial Registration Number: NCT01044862., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To determine if short-term weight change among women with unexplained infertility (UI) and polycystic ovary syndrome (PCOS) undergoing ovulation induction is associated with live birth., Design: Secondary analysis of randomized trials., Setting: Multicenter fertility trial sites., Patient(s): A total of 900 women with UI and 750 women with PCOS., Main Outcome Measure(s): Live birth., Intervention(s): Weight assessment at enrollment and start of up to 4-5 cycles of clomiphene, letrozole, or gonadotropins and intrauterine insemination for women with UI and clomiphene or letrozole with regular intercourse for women with PCOS., Result(s): Weight data were available for 856 women with UI and 697 women with PCOS. Mean weight change was -0.2 ± 0.3 kg among women with UI and +2.2 ± 0.2 kg among women with PCOS and did not differ based on treatment allocation. There were 115 women with PCOS (16.4%) who gained ≥3 kg. Increased body mass index and three or more cycles were associated with weight gain in women with PCOS. There was no difference in live birth rate among women with PCOS and ≥3 kg weight gain and women with PCOS who did not gain weight., Conclusion(s): Women with PCOS gained an average of 2.2 kg regardless of the medication received, whereas women with UI experienced no short-term weight change during ovulation induction. Weight gain in women with PCOS was not associated with live birth rate., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Multiple birth rates after fertility treatment are still high in many countries. Multiple births are associated with increased rates of preterm birth and low birth weight babies, in turn increasing the risk of severe morbidity for the children. The multiple birth rates vary in different countries between 2% and 3% and up to 30% in some settings. Elective single-embryo transfer, particularly in combination with frozen-embryo transfer and milder stimulation in ovulation induction/intrauterine insemination, to avoid multifollicular development is an effective strategy to decrease the multiple birth rates while still achieving acceptable live-birth rates. Although this procedure is used successfully in many countries, it ought to be implemented broadly to improve the health of the children. One at a time should be the normal routine., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Elucidation of multiple waves of antral ovarian follicular development during the menstrual cycle has challenged traditional concepts of female reproductive physiology and foundations of assisted reproductive therapies. Approximately two-thirds of women develop two follicle waves throughout an interovulatory interval and the remainder exhibit three waves of follicle development. Major and minor waves of follicle development have been observed. Major waves are those in which a dominant follicle develops; dominant follicles either regress or ovulate. In minor waves, physiologic selection of a dominant follicle is not manifest. Knowledge of waves of antral follicular development has led to the global adoption of novel ovarian stimulation strategies in which stimulation can be initiated at various times throughout the cycle. Random-start and luteal-phase ovarian stimulation regimens have had important clinical applications for women requiring urgent oocyte or embryo cryopreservation for fertility preservation prior to chemotherapy. Ovarian stimulation twice in the same cycle, referred to as double stimulation, may be used to optimize clinical outcomes in women with a poor ovarian response to stimulation as well as in those requiring fertility preservation before chemotherapy., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)