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Background and ObjectivesPatients with multiple sclerosis (MS) may seek fertility treatment (FT)—including in vitro fertilization (IVF). Variable relapse risk after IVF has been reported in small historical cohorts, with more recent studies suggesting no change in annualized relapse rate (ARR). The objective of this study was to evaluate ARR 12 months pre-FT and 3 months post-FT in a multicenter cohort and identify factors associated with an increased risk of relapse.MethodsPatients with clinically isolated syndrome (CIS) or MS aged 18–45 years with at least 1 FT from January 1, 2010, to October 14, 2021, were retrospectively identified at 4 large academic MS centers. The exposed period of 3 months after FT was compared with the unexposed period of 12 months before FT. FTs included controlled ovarian stimulation followed by fresh embryo transfer (COS-ET), COS alone, embryo transfer (ET) alone, and oral ovulation induction (OI). The Wilcoxon signed rank test and mixed Poisson regression models with random effects were used to compare ARR pre-FT vs post-FT, with the incidence rate ratio (IRR) and 95% CI reported.ResultsOne hundred twenty-four FT cycles among 65 patients with MS (n = 56) or CIS (n = 9) were included: 61 COS-ET, 19 COS alone, 30 ET alone, and 14 OI. The mean age at FT was 36.5 ± 3.8 years, and the mean disease duration was 8.2 ± 5.0 years. Across 80 cycles with COS, only 5 relapses occurred among 4 unique patients within 3 months of treatment. The mean ARR after COS and before was not different (0.26 vs 0.25,p= 0.37), and the IRR was 0.95 (95% CI: 0.52–1.76,p= 0.88). No cycles with therapeutic disease-modifying therapies (DMTs) during COS had 3 months relapse (ARR 0 post-COS vs 0.18 pre-COS,p= 0.02, n = 34). Relapse rates did not vary by COS protocol. Among COS-ET cycles that achieved pregnancy (n = 43), ARR decreased from 0.26 to 0.09 (p= 0.04) within the first trimester of pregnancy. There were no relapses 3 months after ET alone and 1 relapse after OI.DiscussionIn this modern multicenter cohort of patients with MS undergoing diverse FTs, which included 43% on DMTs, we did not observe an elevated relapse risk after FT.

The 2021 Women's Preventive Services Initiative Well-Woman Chart outlines a framework for incorporating preventive health services recommended by the Women's Preventive Services Initiative, the US Preventive Services Task Force, and Bright Futures based on age, health status, and risk factors. Following the previous guidelines for preventive care, this document failed to offer recommendations or guidelines for infertility screening and fertility counseling in the course of well-woman care. Healthcare providers may be less likely to address fertility with their patients in the absence of clear, evidence-based recommendations, potentially resulting in underinformed reproductive choices and compromised reproductive potential. Given the devastating consequences of infertility and unintended childlessness, we, herein, propose that infertility screening and fertility counseling should become an integral part of well-woman care and that organizations, such as the Women's Preventive Services Initiative, put forth guidelines to assist providers in addressing fertility throughout a woman's reproductive lifespan.

The purpose of this review is to update readers on our current understanding of endometrial receptivity and to review the literature regarding endometrial assessment and pathologic states which may influence receptivity. Topics discussed include molecular mechanisms implicated in endometrial receptivity on the basis of which three commercially available yet controversial tests have been developed (Endometrial Function Test, Endometrial Receptivity Assay, and ReceptivaDx), as well as current evidence surrounding how common gynecologic conditions such as polyps, fibroids, adenomyosis, and chronic endometritis may influence endometrial receptivity and the success of assisted reproductive technologies (ART). While the sequential action of estrogen and progesterone is central to the development of endometrial receptivity, the exact molecular mechanisms governing the transition from non-receptive to receptive endometrium remain poorly understood. Commercially available tests attempt to harness molecular markers to assess and potentially improve endometrial receptivity; however, current evidence is insufficient to support their routine clinical application. Polyps, fibroids, adenomyosis, and chronic endometritis may negatively impact implantation either directly by impeding embryo transport and attachment or indirectly by influencing endometrial receptivity. Given the likely heterogenous genetic construct and molecular expression of any pathologic condition, further research is needed to develop molecular testing to guide approach to clinical treatment.

To determine the cost-effectiveness of planned oocyte cryopreservation (OC) as a strategy for delayed childbearing to achieve 1 or 2 live births (LB) compared with in vitro fertilization (IVF) and preimplantation genetic testing for aneuploidy (PGT-A) at advanced reproductive age.Decision tree model with sensitivity analyses using data from the Society for Assisted Reproductive Technology Clinical Outcome Reporting System and other clinical sources.Not applicable.A data-driven simulated cohort of patients desiring delayed childbearing with an ideal family size of 1 or 2 LB.Not applicable.Probability of achieving ≥1 or 2 LB, average and maximum cost per patient, cost per percentage point increase in chance of LB, and population-level cost/LB.For those desiring 1 LB, planned OC at age 33 with warming at age 43 decreased the average total cost per patient from $62,308 to $30,333 and increased the likelihood of LB from 50% to 73% when compared with no OC with up to 3 cycles of IVF/PGT-A at age 43. For those desiring 2 LB, 2 cycles of OC at age 33 and warming at age 40 yielded the lowest cost per patient and highest likelihood of achieving 2 LB ($51,250 and 77%, respectively) when compared withpursuing only 1 cycle of OC ($75,373 and 61%, respectively), no OC and IVF/PGT-A with embryo banking ($79,728 and 48%, respectively), or no OC and IVF/PGT-A without embryo banking ($79,057 and 19%, respectively). Sensitivity analyses showed that OC remained cost-effective across a wide range of ages at cryopreservation. For 1 LB, OC achieved the highest likelihood of success when pursued before age 32 and remained more effective than IVF/PGT-A when pursued before age 39, and for 2 LB, 2 cycles of OC achieved the highest likelihood of success when pursued before age 31 and remained more effective than IVF/PGT-A when pursued before age 39.Among patients planning to postpone childbearing, OC is cost-effective and increases the odds of achieving 1 or 2 LB when compared with IVF/PGT-A at a more advanced reproductive age.

Background The optimal route of progesterone administration for luteal support in cryopreserved embryo transfer (CET) has been the subject of much debate. While most published research has pertained to day 3 transfers, recent data on blastocyst CET has suggested that intramuscular progesterone (IMP) is superior to twice daily vaginal Endometrin suppositories for luteal phase support, resulting in significantly higher ongoing pregnancy rates. This study aimed to determine whether IMP is similarly superior to 8% Crinone vaginal gel for luteal phase support following blastocyst CET. Methods Autologous and donor oocyte blastocyst cryopreserved single embryo transfer (SET) cycles from January 2014–January 2019 utilizing either 50 mg IMP daily or 90 mg 8% Crinone gel twice daily for luteal support were included. The primary outcome was live birth. Secondary outcomes included biochemical pregnancy, spontaneous abortion, and clinical pregnancy. All analyses were adjusted a priori for oocyte age. Log-binomial regression analysis was performed with differences in outcomes reported as relative risk (RR) with 95% confidence intervals (CI). Results A total of 1710 cycles were included, of which 1594 utilized IMP and 116 utilized 8% Crinone gel. Demographic and cycles characteristics were similar between the two groups. Compared to cycles utilizing IMP, cycles utilizing Crinone gel resulted in similar rates of live birth (RR 0.91; 95% CI 0.73–1.13), biochemical pregnancy (RR 1.12, 95% CI 0.65–1.92), spontaneous abortion (RR 1.41, 95% CI 0.90–2.20), and clinical pregnancy (RR 1.00, 95% CI 0.86–1.17). Conclusions Compared to cryopreserved blastocyst SET cycles utilizing IMP for luteal support, cycles utilizing 8% Crinone gel resulted in similar likelihood of live birth.

PURPOSE: To assess the importance of each blastocyst morphological criteria with pregnancy and perinatal outcomes. METHODS: This single-center retrospective cohort study included blastocyst single embryo transfers (SET) performed between 1/2012–2/2018. Poisson regression was used to evaluate pregnancy outcomes following fresh and cryopreserved embryo transfer (CET) for association with blastocyst expansion, inner cell mass (ICM) quality, and trophectoderm (TE) quality. Among cycles resulting in live birth, associations with preterm birth, small for gestational age (SGA) and large for gestational age (LGA), were evaluated using logistic regression. RESULTS: A total of 1023 fresh and 1222 CET cycles were included, of which 465 (45.1%) fresh and 600 (48.5%) CET cycles resulted in singleton live birth. Clinical pregnancy rates increased with increasing expansion among fresh transfers (p for trend = 0.001) but not CET (p = 0.221), and with TE quality for both fresh and CET cycles (p = 0.005 and

Pervasive gender disparities exist in medicine regarding promotion, achievement of academic rank, and appointment to leadership positions. Fertility and childbearing concerns may contribute to these disparities.To assess fertility knowledge and concerns and evaluate barriers to family building and impact on academic attrition reported by female physicians.This qualitative study used mixed methods; first, structured 1:1 interviews exploring fertility knowledge and family-building concerns were conducted among 16 female physicians between November 2019 and May 2020. Transcripts were coded in Dedoose and used to develop a survey instrument with subsequent pilot testing conducted among 24 female physicians between April 2020 and September 2020. Data analysis was performed from January 2021 to March 2021.Fertility knowledge, perceptions of peer and institutional support surrounding childbearing, factors contributing to delayed childbearing, and impact of family planning on career decisions.Among 16 women who completed qualitative interviews, 4 (25%) were Asian, 1 (6%) was Black, 1 (6%) was multiracial, and 10 (63%) were White; mean (SD) age was 34.9 (4.0) years. Evaluation of fertility knowledge revealed 3 notable themes: (1) inadequate formal fertility education, (2) informal learning through infertility experiences of patients, peers, or personal struggles, and (3) desire to improve medical education through early introduction and transparent discussions about infertility. Exploration of childbearing concerns similarly revealed several salient themes: (1) high incidence of delayed childbearing, (2) perceived lack of peer and administrative support, and (3) impact of family building on career trajectory. These themes were borne out in pilot testing of the survey instrument: of 24 female physicians (7 Asian women [27%], 1 Black woman [4%], 1 Hispanic or Latinx woman [4%], 1 multiracial woman [4%], 15 White women [58%]; mean [SD] age, 36.1 [6.7] years), 17 (71%) had delayed childbearing and 16 (67%) had altered their career for family-building reasons.Qualitative interviews identified fertility and family building concerns among female physicians and were used to develop a tailored survey for women in medicine. These findings suggest that female physicians may delay childbearing and make substantial accommodations in their careers to support family building. A large-scale national survey is needed to better characterize the unique fertility, childbearing, and parenting needs of women in academic medicine to better understand how these concerns may contribute to academic attrition.

I have not failed. I've just found 10,000 ways that won't work. -Thomas A. Edison.

Does a shorter follicular phase length (FPL) affect cycle outcomes and endometrial development among women undergoing gonadotrophin ovarian stimulation/intrauterine insemination (OS/IUI)?Retrospective cohort study of 4773 OS/IUI cycles among 2054 patients. FPL was analysed first continuously, then dichotomously using an arbitrary cut-off at the 15th percentile (8 days) to divide cycles into shorter and longer FPL groups. Receiver operating characteristic (ROC) curves were constructed to further analyse the impact of FPL on all outcomes. Primary outcomes included clinical pregnancy, spontaneous abortion, multiple pregnancy and non-viable (ectopic/biochemical) pregnancy rates (CPR, SABR, MPR and NVPR, respectively). Secondary outcomes included endometrial thickness. All analyses controlled for age, day 3 FSH and body mass index.When analysing FPL continuously, CPR increased by 6.0% (adjusted odds ratio [aOR] 1.06, 95% CI 1.03-1.09, P 0.001) with each additional follicular phase day. Similarly, in the dichotomous analysis, cycles with a longer FPL resulted in higher CPR with 45% higher odds of clinical pregnancy (aOR 1.45, 95% CI 1.07-1.97, P = 0.018). No effect of FPL was noted on NVPR, SABR or MPR. Endometrial thickness increased by 0.09 mm (95% CI 0.06-0.12, P 0.001) with each additional FPL day and was increased in the longer compared with the shorter FPL group (adjusted mean difference 1.08 mm, 95% CI 0.81-1.34, P 0.001).The data suggest that in gonadotrophin OS/IUI cycles, FPL might impact both chance of clinical pregnancy and endometrial thickness, independent of maternal age and ovarian reserve.

Study Objective Determine whether patients with endometriosis have a greater likelihood of morbidity at cesarean section. Design Retrospective cohort study Setting Academic hospital Patients or Participants Patients with a singleton pregnancy resulting in primary cesarean delivery between 01/01/2015-12/31/2018. Women with history of surgically-confirmed endometriosis were matched 1:3 to women never diagnosed with endometriosis on delivery year and whether the cesarean was indicated for myomectomy history. Endometriosis was sub-categorized into rASRM stage I/II or stage III/IV by operative findings. Composite morbidity was defined by any transfusion, hysterectomy, or organ injury at cesarean. Additional outcomes included placenta previa, accreta, total surgical time for cesarean, and time from incision to hysterotomy. Multivariable logistic regression models adjusting for age, race, gravidity, IVF conception, and operative hysteroscopy quantified odds ratios(OR) and 95% confidence intervals(CI). Interventions N/A Measurements and Main Results Study population included 384 patients (rASRM stage I/II=44, III/IV=52, no endometriosis=288). Composite morbidity was clinically and statistically significantly greater (17% versus 6%; OR=3.90,CI=1.37-11.05) for stage III/IV patients compared to women without endometriosis. The stage III/IV group also had higher odds of previa (13% versus 3%; OR=4.94,CI=1.45-16.78) and trended towards increased accreta (11% versus 1%; OR=10.18,CI=1.85-55.88) compared to women without endometriosis. Odds of composite morbidity and abnormal placentation were similar comparing stage I/II endometriosis patients to women without endometriosis. Time from skin to uterine incision did not differ between either endometriosis group and women without endometriosis, while stage III/IV patients were more likely to have a surgical time >1 hour (OR=2.49,CI=1.21-5.11). Conclusion Among patients who had a singleton pregnancy resulting in primary cesarean delivery, women with a history of stage III/IV endometriosis had greater odds of placenta previa, and surgical morbidity compared to patients without endometriosis. These findings suggest that one or more characteristics of rASRM stage III/IV may be related to abnormal placentation and morbidity at cesarean delivery, and endometriosis phenotypes should be better documented and further explored.

Since the first successful human in vitro fertilization (IVF) pregnancy nearly 40 years ago, remarkable progress has been made in assisted reproductive technology (ART). Improvements in oocyte retrieval, embryo culture, genetic screening, and embryo selection have contributed to dramatic improvements in IVF outcomes. A more robust understanding of embryologic development has driven innovation in not only the timing of embryo transfer but also the number of embryos to transfer. Additionally, overcoming the technical hurdle of embryo vitrification has given both physicians and patients several benefits including the flexibility to mitigate effects of superovulation on the endometrium, limit the number of embryos transferred, afforded an opportunity to screen the quality of embryos both by evaluating in vitro development as well as preimplantation genetic testing. Within this review, we highlight in a stepwise fashion the considerations for embryo transfer timing and technique that physicians and patients alike must consider when undergoing an IVF cycle.