Initiation and outcomes of women pursuing planned fertility preservation.

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. INTERVENTION(S): 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.

A Mixed-Methods Study to Evaluate Family Planning Desires and Barriers to Building Families Among Gay, Bisexual, and Lesbian Cisgender Military Service Members.

INTRODUCTION: Barriers to seeking infertility care for lesbian, gay, bisexual, transgender, intersex, queer/questioning, and asexual (LGBTIQA+) individuals are well documented in the literature. However, little is known about military LGBTIQA+ service members seeking infertility care within the Military Health System. Approximately 6.1% of active duty U.S. service members across all branches identify as LGBTIQA+, which underscores the need for a deeper understanding of the needs of this community to support and retain service members. We therefore sought to describe the lived experiences of lesbian and gay cisgender service members in building their families in order to understand their family-building desires and potential barriers to seeking infertility care. MATERIALS AND METHODS: We developed a survey to investigate the impact of military service on family planning. After Institutional Review Board approval, we distributed the survey throughout Walter Reed National Military Medical Center's obstetrics and gynecology clinic and posted the survey on multiple open and closed social media pages for LGBTIQA+ service members. We reported descriptive statistics of our survey and compared binary variables using the Fisher exact test. Following completion of this survey, participants could self-select to participate in semi-structured interviews. RESULTS: Sixty-eight respondents completed our survey and self-identified as either cis-male (n = 28) or cis-female (n = 40). Most respondents (67.9% cis-males, 92.5% cis-females) plan to build their families during their military commitment; however, approximately half (50.0% cis-male, 42.5% cis-female) reported a lack of support in this endeavor. Many respondents were unaware of resources that would assist in the pursuit of donor egg, donor sperm, or surrogacy (78.6% cis-males, 50.0% cis-females). Thirty-six participants elected to complete a follow-up interview. After coding the interviews, 5 themes emerged: (1) barriers to initiating care; (2) institutional barriers within the military; (3) political barriers; (4) knowledge sharing; and (5) implicit and explicit bias. CONCLUSIONS: Our results suggest significant barriers to LGBTIQA+ service members seeking infertility care. Overall, LGBTIQA+ service members did not feel supported by the military in building their families. Although the military has expanded access to infertility services, efforts to raise awareness and build support for LGBTIQA+ service members are warranted.

Cephalopagus twins diagnosed at 7 weeks gestational age following IVF/ICSI.

A patient in her 30s who was a G0 proceeded with in vitro fertilisation (IVF) for a history of male factor infertility. Following single embryo transfer, the patient was diagnosed with a conjoined twin pregnancy. During her IVF cycle, the patient was stimulated with an antagonist protocol for 13 days followed by a gonadotropin-releasing hormone agonist trigger. 13 eggs were retrieved, 9 were mature and 5 fertilised with intracytoplasmic sperm injection. Of those, two were cryopreserved. She had a successful frozen blastocyst embryo transfer. The patient's 7-week ultrasound demonstrated a single gestational sac, yolk sac and fetal pole. However, the crown-rump length appeared visually abnormal and two heartbeats were visualised. She was referred to maternal-fetal medicine (MFM) for a first-trimester ultrasound. Her ultrasound with MFM was notable for a fluid-filled chest, foreshortened limbs and early sacral agenesis. She was subsequently diagnosed with cephalopagus twins and underwent an induced abortion following consultation with MFM.

Assessment of clinical pregnancies in up to eight ovarian stimulation with intrauterine insemination treatment cycles in those unable to proceed with in vitro fertilization.

OBJECTIVE: To study the primary objective of clinical pregnancy (CP) rate per ovarian stimulation with intrauterine insemination (OS-IUI) treatment cycle in patients with repetitive cycles up to a maximum of 8 cycles. DESIGN: Retrospective cohort. SETTING: Large fertility clinic. PATIENTS: A total of 37,565 consecutive OS-IUI cycles from 18,509 patients were included in this study. INTERVENTIONS: Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. The CP rate was analyzed using generalized estimating equations and controlled for age, stimulation protocol, and body mass index. MAIN OUTCOMES MEASURES: Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. RESULTS: A total of 37,565 consecutive OS-IUI cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients aged <35 years comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of CP for cycles one to 8 was 15.7% per cycle. The mean predicted probability of CP in aggregated data from cycles 2 to 4 was only 1.7% lower compared with cycle 1 as the referent (16.7% vs. 15.0%, 95% confidence interval [CI] 2nd: 0.88 {0.82, 0.95}, 3rd: 0.86 {0.79, 0.93}, 4th: 0.88 {0.79, 0.98}). However, the 15.0% mean predicted probability of CP for the second through the fourth cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of CP of cycles 5 to 8 was not significantly different compared with the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 [0.85, 1.11], 6th: 0.93 [0.79, 1.10], 7th: 1.01 [0.81, 1.26], 8th: 1.01 [0.76, 1.34]). The modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of CP from OS-IUI continues to increase with each of the 8 successive cycles. CONCLUSION: Clinical pregnancy rates are satisfactory in up to 8 consecutive OS-IUI treatment cycles. These data are useful for counseling, especially in those patients for whom in vitro fertilization is not financially or ethically feasible.

Meeting the demand for fertility services: the present and future of reproductive endocrinology and infertility in the United States.

The field of reproductive endocrinology and infertility (REI) is at a crossroads; there is a mismatch between demand for reproductive endocrinology, infertility and assisted reproductive technology (ART) services, and availability of care. This document's focus is to provide data justifying the critical need for increased provision of fertility services in the United States now and into the future, offer approaches to rectify the developing physician shortage problem, and suggest a framework for the discussion on how to meet that increase in demand. The Society of REI recommend the following: 1. Our field should aggressively explore and implement courses of action to increase the number of qualified, highly trained REI physicians trained annually. We recommend efforts to increase the number of REI fellowships and the size complement of existing fellowships be prioritized where possible. These courses of action include: a. Increase the number of REI fellowship training programs. b. Increase the number of fellows trained at current REI fellowship programs. c. The pros and cons of a 2-year focused clinical fellowship track for fellows interested primarily in ART practice were extensively explored. We do not recommend shortening the REI fellowship to 2 years at this time, because efforts should be focused on increasing the number of fellowship training slots (1a and b). 2. It is recommended that the field aggressively implements courses of action to increase the number of and appropriate usage of non-REI providers to increase clinical efficiency under appropriate board-certified REI physician supervision. 3. Automating processes through technologic improvements can free providers at all levels to practice at the top of their license.

Preimplantation genetic testing for sickle cell disease: a cost-effectiveness analysis.

Objective: To evaluate the cost-effectiveness of in vitro fertilization with preimplantation genetic testing for monogenic disease (IVF + PGT-M) in the conception of a nonsickle cell disease (non-SCD) individual compared with standard of care treatment for a naturally conceived, sickle cell disease (SCD)-affected individual. Design: A Markov simulation model was constructed to evaluate a one-time IVF + PGT-M treatment compared with the lifetime standard of care costs of treatment for an individual potentially born with SCD. Using an annual discount rate of 3% for cost and outcome measures, quality-adjusted life years were constructed from utility weights and life expectancy values and then used as the effectiveness measurement. An incremental cost-effectiveness ratio was calculated for both treatment arms, and a willingness-to-pay threshold of $50,000 per quality-adjusted life year was assumed. Setting: Tertiary care or university medical center. Patients: A hypothetical cohort of 10,000 patients was analzyed over a lifetime horizon using yearly cycles. Interventions: In vitro fertilization with preimplantation genetic testing for monogenic disease use in conception of a non-SCD individual. Main Outcome Measures: The primary outcomes of interest were the incremental cost and effectiveness of an IVF+PGT-M conception compared with the SOC treatment of an SCD-affected individual. Results: In vitro fertilization with preimplantation genetic testing for monogenic disease was the optimal strategy in 93.17% of the iterations. An incremental savings of $137,594 was demonstrated with a gain of 1.96 QALYs and 3.69 life years over a lifetime. Sensitivity analysis demonstrated that SOC treatment never met equivalent cost-effectiveness. Conclusions: Our model demonstrates that IVF + PGT-M for selection against SCD, compared with lifetime SOC treatment for those affected, is the most cost-effective strategy within the United States healthcare sector.

Reproductive genetics laboratory may impact euploid blastocyst and live birth rates: a comparison of 4 national laboratories' PGT-A results from vitrified donor oocytes.

OBJECTIVE: To evaluate potential variation in the euploid blastocyst rate and live birth rate (LBR) per single frozen euploid blastocyst transfer, among 4 unique United States reproductive genetics laboratories. Analyses were limited to blastocysts derived from vitrified donor oocytes, to minimize variation in oocyte quality. DESIGN: Retrospective cohort study from 2016 to 2020. SETTING: Donor Egg Bank Database. PATIENT(S): Patients undergoing in vitro fertilization with donor oocytes. We excluded patients with uterine factor, male factor, or surgically extracted sperm. Only healthy women <34 years old were accepted as oocyte donors. INTERVENTION(S): Next generation sequencing platforms for chromosomal analysis MAIN OUTCOME MEASURE(S): Euploid blastocyst rate and LBR per euploid transfer. Secondary outcomes included the rate of aneuploidy, mosaic calls, biochemical pregnancy loss, and miscarriage rate. RESULT(S): A total of 2,633 embryos were included. Four laboratories had >200 embryos tested. Euploid blastocyst rate was significantly higher in laboratory A (73.6%) vs. B (63.3%), C (60.9%), and D (52.3%). Mosaic rate was significantly lower for Laboratories B (2.8%) and C (5.5%) vs. Laboratories A (9.9%) and D (11.5). The LBR was significantly higher in laboratory A (58.73%) vs. laboratory D (47.3%). There were no significant differences in the implantation or miscarriage rate among laboratories. CONCLUSION(S): In this large study, controlling for oocyte quality, some preimplantation genetic testing for aneuploidy (PGT-A) laboratories report a significantly higher euploid blastocyst rate with concurrent higher LBR. This type of comparison is important as it provides insight into the role of the PGT-A process in outcomes. Further research is needed to evaluate the differences in laboratory techniques and bioinformatic algorithms accounting for variable outcomes across PGT-A laboratories.

Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial.

Importance: Endometrial receptivity testing is purported to improve live birth following frozen embryo transfer by identifying the optimal embryo transfer time for an individual patient; however, data are conflicting. Objective: To compare live birth from single euploid frozen embryo transfer according to endometrial receptivity testing vs standardized timing. Design, Setting, and Participants: Double-blind, randomized clinical trial at 30 sites within a multicenter private fertility practice in the Eastern US. Enrollment was from May 2018 to September 2020; follow-up concluded in August 2021. Participants underwent in vitro fertilization, preimplantation genetic testing for aneuploidy, endometrial receptivity testing, and frozen embryo transfer. Those with euploid blastocyst(s) and an informative receptivity result were randomized. Exclusion criteria included recurrent pregnancy loss, recurrent implantation failure, surgically aspirated sperm, donor egg(s), and unmitigated anatomic uterine cavity defects. Interventions: The intervention group (n = 381) underwent receptivity-timed frozen embryo transfer, with adjusted duration of progesterone exposure prior to transfer, if indicated by receptivity testing. The control group (n = 386) underwent transfer at standard timing, regardless of receptivity test results. Main Outcomes and Measures: The primary outcome was live birth. There were 3 secondary outcomes, including biochemical pregnancy and clinical pregnancy. Results: Among 767 participants who were randomized (mean age, 35 years), 755 (98%) completed the trial. All randomized participants were analyzed. The primary outcome of live birth occurred in 58.5% of transfers (223 of 381) in the intervention group vs 61.9% of transfers (239 of 386) in the control group (difference, -3.4% [95% CI, -10.3% to 3.5%]; rate ratio [RR], 0.95 [95% CI, 0.79 to 1.13]; P = .38). There were no significant differences in the intervention vs the control group for the prespecified secondary outcomes, including biochemical pregnancy rate (77.2% vs 79.5%, respectively; difference, -2.3% [95% CI, -8.2% to 3.5%]; RR, 0.97 [95% CI, 0.83 to 1.14]; P = .48) and clinical pregnancy rate (68.8% vs 72.8%, respectively; difference, -4.0% [95% CI, -10.4% to 2.4%]; RR, 0.94 [95% CI, 0.80 to 1.12]; P = .25). There were no reported adverse events. Conclusions and Relevance: Among patients for whom in vitro fertilization yielded a euploid blastocyst, the use of receptivity testing to guide the timing of frozen embryo transfer, compared with standard timing for transfer, did not significantly improve the rate of live birth. The findings do not support routine use of receptivity testing to guide the timing of embryo transfer during in vitro fertilization. Trial Registration: ClinicalTrials.gov Identifier: NCT03558399.

The impact of the COVID-19 pandemic on gestational carriers.

Reproductive medicine has been significantly impacted by the coronavirus (COVID-19) pandemic, and this includes the gestational carrier (GC) process. The objectives of this commentary are to evaluate the impact of COVID-19 on the GC process, as well to communicate Shady Grove Fertility's considerations of and response to COVID-19 on the GC process to the larger assisted reproductive technology (ART) community. We also gathered conclusions drawn from available data on the impact of COVID-19 infection on maternal and neonatal morbidity and mortality as well as on counseling patients on vaccination. We compiled proposals to mitigate risk and to maximize safe evaluation and treatment for GCs during the ongoing pandemic. Over 2 years after the onset of the pandemic, the multiple resurgences of cases in the USA have necessitated nimble strategies to provide ongoing and safe reproductive care and have posed unique challenges to the GC process. With the prospect of the virus continuing to spread globally well into the future, as healthcare professionals of the ART community, we will need to ensure effective collaboration and communication as we provide care during the ongoing pandemic.

Preconception hemoglobin A1c concentration in healthy women is not associated with fecundability or pregnancy loss.

Objective: To examine the relationship of preconception hemoglobin A1c, a marker of cumulative exposure to glucose over the preceding 2-3 months, with time to pregnancy, pregnancy loss, and live birth among fecund women without diagnosed diabetes or other medical diseases. Design: A secondary analysis of a prospective cohort of women participating in the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial. Setting: Four US academic medical centers. Patients: A total of 1,194 healthy women aged 18-40 years with a history of one or two pregnancy losses attempting spontaneous conception were observed for up to six cycles while attempting pregnancy and throughout pregnancy if they conceived. Interventions: Not applicable. Main Outcome Measures: Time to pregnancy, human chorionic gonadotropin pregnancy, clinical pregnancy, pregnancy loss, and live birth. Results: Although increasing preconception A1c level was associated with reduced fecundability (fecundability odds ratio [FOR] per unit increase in A1c 0.74; 95% confidence interval [CI] 0.57, 0.96) in unadjusted models and models adjusted for age, race, smoking and treatment arm (FOR 0.79; 95% CI 0.60, 1.04), results were attenuated after further adjustment for body mass index (FOR 0.91; 95% CI 0.68, 1.21). Preconception A1c levels among women without diagnosed diabetes were not associated with live birth or pregnancy loss. Conclusionss: Among healthy women without diagnosed diabetes, we observed no association of A1c with live birth or pregnancy loss. The association between A1c and fecundability was influenced by body mass index, a strong risk factor for both diabetes and infertility. These data support current recommendations that preconception A1c screening should be reserved for patients with risk factors for diabetes. Clinical Trial Registration Number: ClinicalTrials.gov: NCT00467363.

The Safety of Low-Dose Aspirin on the Mode of Delivery: Secondary Analysis of the Effect of Aspirin in Gestation and Reproduction Randomized Controlled Trial.

OBJECTIVE: This study aimed to examine whether prenatal low-dose aspirin (LDA) therapy affects risk of cesarean versus vaginal delivery. STUDY DESIGN: This study is a secondary analysis of the randomized clinical effects of aspirin in gestation and reproduction (EAGeR) trial. Women received 81-mg daily aspirin or placebo from preconception to 36 weeks of gestation. Mode of delivery and obstetric complications were abstracted from records. Log-binomial regression models estimated relative risk (RR) of cesarean versus vaginal delivery. Data were analyzed among the total preconception cohort, as well as restricted to women who had a live birth. RESULTS: Among 1,228 women, 597 had a live birth. In the intent-to-treat analysis, preconception-initiated LDA was not associated with risk of cesarean (RR = 1.02; 95% confidence interval [CI]: 0.98-1.07) compared with placebo. Findings were similar in just women with a live birth and when accounting prior cesarean delivery and parity. CONCLUSION: Preconception-initiated daily LDA was not associated with mode of delivery among women with one to two prior losses. KEY POINTS: · Aspirin was not associated with risk of cesarean section.. · Aspirin was not associated with mode of delivery.. · No increased risk of bleeding with use of aspirin..

Common practices among consistently high-performing in vitro fertilization programs in the United States: 10-year update.

OBJECTIVE: To evaluate similarities and differences in clinical and laboratory practices among high-performing fertility clinics. DESIGN: Cross-sectional questionnaire study of selected programs. SETTING: Academic and private fertility practices performing in vitro fertilization (IVF). PATIENT(S): Not applicable. INTERVENTION(S): A comprehensive survey was conducted of 13 IVF programs performing at least 100 cycles a year and having high cumulative singleton delivery rates for 2 years. MAIN OUTCOME MEASURE(S): Clinical and laboratory IVF practices. RESULT(S): Although many areas of clinical practice varied among top programs, some commonalities were observed. All programs used a combination of follicle-stimulating hormone and luteinizing hormone for IVF stimulation, intramuscular progesterone in frozen embryo transfer cycles, ultrasound-guided embryo transfers, and a required semen analysis before starting the IVF cycle. Common laboratory practices included vitrification of embryos at the blastocyst stage, air quality control with positive air pressure and high-efficiency particulate air filtration, use of incubator gas filters, working on heated microscope stages, and incubating embryos in a low-oxygen environment, most often in benchtop incubators. CONCLUSION(S): Some areas of consistency in clinical and laboratory practices were noted among high-performing IVF programs that are likely contributing to their success. High-performing programs focused on singleton deliveries. As the field of IVF is rapidly evolving, it is imperative that we share best practices in an effort to improve outcomes from all clinics for the good of our patients.

Recurrent implantation failure: Sapereaude.

Recurrent implantation failure is a challenging clinical dilemma, without consensus diagnostic criteria. Current evidence provides a starting point for clinical investigation and treatment, while novel therapeutics are being investigated. Ultimately, a consensus diagnosis is needed to inform clinical management and future investigation.