Family Building in Transgender Patients: Modern Strategies with Assisted Reproductive Technology Treatment.

Purpose: Transgender and gender diverse (TGD) individuals continue to face adversity, stigma, and inequality, especially in health care. This study aimed to characterize the experience of TGD people and partners of TGD people with regard to fertility treatment. Methods: All TGD patients presenting to a single academic center between 2013 and 2021 were included. Baseline demographics collected included patient age, body mass index, anti-Mullerian hormone, basal antral follicle count, history of gender-affirming surgery, and/or gender-affirming hormone therapy. Outcomes included total patients who progressed to treatment, cycle type(s), and clinical outcomes. Results: In total, 82 patients who identified as TGD or had a partner who identified as TGD presented to care seeking fertility treatment. Of the 141 planned cycles, 106 (75.2%) progressed to treatment. Of the 15 in vitro fertilization (IVF) and co-IVF cycles, 12 achieved live birth. Of the 76 intrauterine inseminations 7 patients were discharged with ongoing pregnancies and one achieved live birth. Conclusion: These findings reaffirm that TGD individuals utilize the entire array of fertility services. With recent advances in access to care and modern medicine, assisted reproductive technology treatment has the power to support TGD patients in building contemporary family structures.

Fertility treatment outcomes in transgender men with a history of testosterone therapy.

Objective: To evaluate fertility treatment outcomes among transgender (TG) men with a history of gender-affirming hormone therapy with exogenous testosterone. Design: Descriptive, retrospective cohort study. Patients: Transgender men with a history of gender-affirming hormone therapy with exogenous testosterone underwent fertility treatments, including embryo cryopreservation, in vitro fertilization (IVF), co-IVF, oocyte cryopreservation, and intrauterine insemination (IUI), between 2013 and 2021. Intervention: Gender-affirming hormone therapy with testosterone. Main Outcome Measures: Live births (LBs), number of frozen embryos, and number of frozen oocytes. Other outcome measures included total gonadotropin used, peak estradiol levels, oocytes retrieved, oocyte maturity rate, fertilization rate, and embryo grade. Results: A total of 77 TG men self-presented or were referred to care at a single academic fertility center, of which 46 (59.7%) TG men underwent fertility preservation and/or family-building counseling, with 16 (20.8%) patients proceeding to fertility treatment. Of those patients who underwent treatment, 11 (68.8%) had a history of gender-affirming hormone therapy with exogenous testosterone use. Cohort 1 included IVF (n = 1), co-IVF (n = 1), embryo cryopreservation (n = 2), cohort 2 included oocyte cryopreservation (n = 4), and cohort 3 included IUI (n = 3). In cohort 1, both the patients who underwent IVF and the patients who underwent co-IVF achieved LBs. All embryo cryopreservation cycles froze three or more embryos. In cohort 2, the average number of frozen mature oocytes was 19.3 ± 16.2 (range 6-43). All patients who underwent IUI cycles achieved LB. Conclusion: In this study, no correlation existed between patient age, time on or off gender-affirming hormone therapy with exogenous testosterone, total gonadotropin used, and number of oocytes retrieved. All patients who completed IVF or embryo cryopreservation produced high-quality blastocytes, and this is the first study to show successful IUI cycles in patients with a history of gender-affirming hormone therapy with exogenous testosterone. This study demonstrates that TG men who have used gender-affirming hormone therapy previously can successfully undergo fertility treatments to attain oocyte and embryo cryopreservation, pregnancy, and LBs.

Association of Myomectomy With Anti-Müllerian Hormone Levels and Ovarian Reserve.

OBJECTIVE: To assess whether open and minimally invasive myomectomy are associated with changes in postoperative ovarian reserve as measured by serum anti-müllerian hormone (AMH) level. METHODS: This prospective cohort study included patients who were undergoing open abdominal myomectomy that used a tourniquet or minimally invasive (robot-assisted or laparoscopic) myomectomy that used vasopressin. Serum AMH levels were collected before the procedure and at 2 weeks, 3 months, and 6 months after surgery. The mean change in AMH level at each postsurgery timepoint was compared with baseline. The effect of surgical route on the change in AMH level at each timepoint was assessed by using multivariable linear regression. A subanalysis evaluated postoperative changes in AMH levels among the open myomectomy and minimally invasive myomectomy groups individually. RESULTS: The study included 111 patients (mean age 37.9±4.7 years), of whom 65 underwent open myomectomy and 46 underwent minimally invasive myomectomy. Eighty-seven patients contributed follow-up data. Serum AMH levels declined significantly at 2 weeks postsurgery (mean change -0.30 ng/mL, 95% CI -0.48 to -0.120 ng/mL, P=.002). No difference was observed at 3 months or 6 months postsurgery. On multiple linear regression, open myomectomy was significantly associated with a decline in AMH level at 2 weeks postsurgery (open myomectomy vs minimally invasive myomectomy: ß=-0.63±0.22 ng/mL, P=.007) but not at 3 months or 6 months. Subanalysis revealed a significant decline in mean serum AMH levels in the open myomectomy group at 2 weeks (mean change -0.46 ng/mL, 95% CI -0.69 to -0.25 ng/mL, P<.001) postsurgery but not at three or 6 months. In the minimally invasive myomectomy group, no significant differences in mean AMH levels were detected between baseline and any postoperative timepoint. CONCLUSION: Myomectomy is associated with a transient decline in AMH levels in the immediate postoperative period, particularly after open surgery in which a tourniquet is used. Anti-müllerian hormone levels returned to baseline by 3 months after surgery, indicating that myomectomy is not associated with a long-term effect on ovarian reserve, even with the use of a tourniquet to decrease blood loss. FUNDING SOURCE: This study was funded in part by a Roche Diagnostics Investigator-Initiated Study Grant.

Maternal and neonatal outcomes of trial of labor compared with elective cesarean delivery according to predicted likelihood of vaginal delivery.

OBJECTIVE: The vaginal birth after cesarean (VBAC) calculator developed by the Maternal-Fetal Medicine Units Network (MFMU) helps to identify the likelihood of VBAC. We sought to compare adverse maternal and neonatal outcomes of trial of labor after cesarean (TOLAC) to those of elective cesarean delivery after stratifying by VBAC likelihood. STUDY DESIGN: This was a retrospective cohort study of all women whose primary low transverse segment cesarean delivery and subsequent singleton term delivery with vertex presentation occurred at an academic center from January 2009 to June 2018. Only data from the second pregnancy were analyzed. The final analysis included 835 women. The MFMU VBAC calculator was used to assess the likelihood of VBAC. The two primary outcomes were composite adverse maternal (death or severe maternal complications) and neonatal outcomes (perinatal death or severe neonatal complications). The analyses were stratified based on the VBAC likelihood (less than 60% and 60-100%). Multivariable logistic regression was used to calculate adjusted odds ratio (OR) and 95% confidence interval (CI), controlling for predefined covariates. RESULTS: Among women with VBAC likelihood less than 60%, TOLAC compared with elective cesarean was associated with increased odds of the primary adverse maternal outcome (16.4% vs. 4.2%; adjusted OR 4.60 [95%CI 1.48-14.35]) and the primary adverse neonatal outcome (17.8% vs. 6.3%; adjusted OR 3.93 [95%CI 1.31-11.75]). Among women with VBAC likelihood of 60-100%, TOLAC compared with elective cesarean was associated with decreased odds of the primary adverse maternal outcome (6.4% vs. 11%; adjusted OR 0.47 [95%CI 0.25-0.89]) and similar odds of the primary adverse neonatal outcome (6.7% vs. 8.3%; adjusted OR 0.98 [95%CI 0.52-1.84]). CONCLUSIONS: Among women with a history of a primary low transverse cesarean delivery, those who underwent TOLAC compared to those who had elective cesarean had increased odds of adverse maternal and neonatal outcomes when VBAC likelihood was less than 60%.

In Vitro Fertilization and Early Pregnancy Outcomes After Coronavirus Disease 2019 (COVID-19) Vaccination.

OBJECTIVE: To assess whether coronavirus disease 2019 (COVID-19) mRNA vaccination is associated with controlled ovarian hyperstimulation or early pregnancy outcomes. METHODS: This retrospective cohort study included patients who underwent controlled ovarian hyperstimulation or single euploid frozen-thawed embryo transfer at a single academic center. Patients fully vaccinated with a COVID-19 mRNA vaccine were compared with unvaccinated patients who cycled during the same time period. The primary outcome was the fertilization rate for controlled ovarian hyperstimulation and the clinical pregnancy rate for frozen-thawed embryo transfer. Secondary outcomes for controlled ovarian hyperstimulation included eggs retrieved, mature oocytes retrieved, mature oocytes ratio, blastulation rate, and euploid rate. Secondary outcomes for frozen-thawed embryo transfer included pregnancy rate, ongoing pregnancy rate, biochemical pregnancy loss rate, and clinical pregnancy loss rate. RESULTS: Among 222 vaccinated patients and 983 unvaccinated patients who underwent controlled ovarian hyperstimulation cycles between February and September 2021, there was no association on adjusted analysis between COVID-19 vaccination and fertilization rate (ß=0.02±0.02, P=.20) or any of the secondary outcomes assessed: eggs retrieved (ß=0.01±0.57, P=.99), mature oocytes retrieved (ß=0.26±0.47, P=.58), mature oocytes ratio (ß=0.02±0.01, P=.12), blastulation rate (ß=0.02±0.02, P=.27), or euploid rate (ß=0.05±0.03, P=.08). Among 214 vaccinated patients and 733 unvaccinated patients undergoing single euploid frozen-thawed embryo transfer, adjusted analysis demonstrated no significant association between vaccination and clinical pregnancy (adjusted odds ratio [aOR] 0.79, 95% CI 0.54-1.16) or any of the secondary outcomes: pregnancy (aOR 0.88, 95% CI 0.58-1.33), ongoing pregnancy (aOR 0.90, 95% CI 0.61-1.31), biochemical pregnancy loss (aOR 1.21, 95% CI 0.69-2.14), or clinical pregnancy loss (aOR 1.02, 95% CI 0.51-2.06). CONCLUSION: Administration of COVID-19 mRNA vaccines was not associated with an adverse effect on stimulation or early pregnancy outcomes after IVF. Our findings contribute to the growing body of evidence regarding the safety of COVID-19 vaccination in women who are trying to conceive.

Interpregnancy body mass index change and risk of hypertensive disorders in pregnancy.

BACKGROUND: Hypertensive disorders are a common cause of maternal mortality. Whether interpregnancy BMI (body mass index kg/m2) gain is associated with hypertensive disorders in a subsequent pregnancy is not unclear. OBJECTIVES: To examine the association between interpregnancy BMI and hypertensive disorders in women without a history of hypertensive disorders in pregnancy. STUDY DESIGN: This was a retrospective cohort study of all women who had more than one singleton pregnancy at 23 weeks' gestation or greater at a single academic institution. Only the second pregnancy in the dataset was analyzed. We excluded women who had any hypertensive disorder in the index pregnancy. Interpregnancy BMI change was calculated by the change of early pregnancy BMI (within 14 weeks' gestation) measured in the office between the index pregnancy compared to that of the subsequent pregnancy. Women were categorized according to interpregnancy BMI change (BMI loss greater than 2 kg/m2, BMI change ±2 kg/m2, and BMI gain greater than 2 kg/m2). The primary outcome was any hypertensive disorder (chronic hypertension and pregnancy-associated hypertension). Multivariable logistic regression was performed to calculate adjusted odds ratios (aOR) with 95% confidence interval (95%CI) after adjusting for predefined covariates. RESULTS: Of 3068 women who were analyzed, 342 (11%), 1698 (55%), and 1028 (34%) had interpregnancy BMI loss greater than 2 kg/m2, interpregnancy BMI change ±2 kg/m2, and interpregnancy BMI gain greater than 2 kg/m2, respectively. Interpregnancy BMI gain greater than 2 kg/m2 compared to interpregnancy BMI loss more than 2 kg/m2 was associated with increased odds of hypertensive disorders (8.3% vs. 4.0%; adjusted odds ratio 2.20 [95% confidence interval 1.55-3.13]) and pregnancy-associated hypertension (adjusted odds ratio 2.25 [95% confidence interval 1.54-3.27]). Interpregnancy BMI loss greater than 2 kg/m2 compared to interpregnancy BMI change ±2 kg/m2 was not associated with increased odds of any hypertensive disorders (5.3% vs. 4.0%; adjusted odds ratio 0.58 [95% confidence interval 0.32-1.05]). CONCLUSIONS: Compared to interpregnancy BMI change ±2 kg/m2, interpregnancy BMI gain greater than 2 kg/m2 was associated with increased odds of any hypertensive disorder. Weight control after pregnancy could be a potentially modifiable factor that may reduce the risk of hypertensive disorders.

Interpregnancy Body Mass Index Change and Risk of Intrapartum Cesarean Delivery.

OBJECTIVE: This study aimed to examine the association between interpregnancy body mass index (BMI, kg/m2) change and intrapartum cesarean delivery in multiparous women without a history of cesarean delivery. STUDY DESIGN: We conducted a retrospective cohort study of all women who had more than one singleton pregnancy at 23 weeks' gestation or greater at MedStar Washington Hospital Center from January 2009 to June 2018. We excluded women who had a history of cesarean delivery, prelabor cesarean delivery, and contraindications for vaginal delivery. Interpregnancy BMI change was calculated by the change of early pregnancy BMI measured in the office. Women were categorized according to the interpregnancy BMI change (BMI loss more than 2 kg/m2, BMI change ± 2 kg/m2, and BMI gain more than 2 kg/m2). The primary outcome was an intrapartum cesarean delivery. Multivariable logistic regression was performed to calculate adjusted odds ratio (aOR) with 95% confidence interval (CI) after adjusting for predefined covariates. RESULTS: Of 2,168 women who were analyzed, 258 (12%), 1,192 (55%), and 718 (33%) had interpregnancy BMI loss more than 2 kg/m2, BMI change ± 2 kg/m2, and BMI gain more than 2 kg/m2, respectively. Women with BMI gain more than 2 kg/m2 compared with those with BMI change ± 2 kg/m2 had increased odds of intrapartum cesarean delivery (7.4 vs. 4.5%; aOR: 1.78; 95% CI: 1.10-2.86) and cesarean delivery for arrest disorders (3.1 vs. 1.1%; aOR: 3.06; 95% CI: 1.30-7.15). Women with BMI loss more than 2 kg/m2 compared with those with BMI change ± 2 kg/m2 had similar rates of cesarean delivery. CONCLUSION: Compared with interpregnancy BMI change ± 2 kg/m2, interpregnancy BMI gain 2 kg/m2 was associated with increased odds of intrapartum cesarean delivery. KEY POINTS: · BMI gain between pregnancies was associated with intrapartum cesarean delivery.. · BMI loss between pregnancies was not associated with intrapartum cesarean delivery.. · Our study suggests that at least maintaining weight between pregnancies is beneficial..

Association between long interpregnancy intervals and cesarean delivery due to arrest disorders.

BACKGROUND: It is hypothesized that pregnancy causes time-limited physiologic adaptations of the reproductive system, such as increased blood flow to the uterus. With long interpregnancy intervals, those adaptations may regress, and maternal physiologic characteristics may revert to those of primigravid women. Therefore, it is plausible that long interpregnancy interval is associated with cesarean delivery, especially due to arrest disorders (failed induction of labor, arrest of dilation, or arrest of descent). OBJECTIVE: To examine the association between interpregnancy interval and cesarean delivery due to arrest disorders in multiparous women without a history of cesarean delivery. MATERIALS AND METHODS: This was a retrospective cohort study of all women who had more than 1 singleton pregnancy at 23 weeks' gestation or greater at MedStar Washington Hospital Center from January 2009 to June 2018. We defined the interpregnancy interval as the duration from the birth of the preceding offspring to the date of conception of the index offspring. We a priori decided to categorize women based on the interpregnancy interval (less than 18 months, 18-59 months, and 60 months or greater). Our primary outcome was cesarean delivery due to arrest disorders. We also examined overall cesarean delivery and cesarean delivery due to nonreassuring fetal heart tracing. Multivariable logistic regression was performed to calculate adjusted odds ratios and 95% confidence intervals, controlling for predefined covariates. RESULTS: Of 2741 women, 1143 (41.7%), 1369 (49.9%), and 229 (8.4%) had an interpregnancy interval of less than 18 months, 18-59 months, and 60 months or more, respectively. After adjusting for confounders, an interpregnancy interval of 60 months or more compared to an interpregnancy interval of 18-59 months was associated with increased odds of cesarean delivery due to arrest disorders (4.8% vs 1.3%; adjusted odds ratio, 3.06; 95% confidence interval, 1.34-6.97) and cesarean delivery due to arrest of dilation (3.1% vs 0.7%; adjusted odds ratio, 3.24; 95% confidence interval, 1.10-9.59). An interpregnancy interval of less than 18 months compared to an interpregnancy interval of 18-59 months was associated with decreased odds of cesarean delivery due to nonreassuring fetal heart tracing (2.4% vs 4.1%; adjusted odds ratio, 0.55; 95% confidence interval, 0.32-0.92). CONCLUSION: An interpregnancy interval of 60 months or greater compared to an interpregnancy interval of 18-59 months was associated with increased odds of cesarean delivery due to arrest disorders. Beneficial effects on postpartum adaptations in the reproductive system may regress as interpregnancy interval increases.

Wheel running reduces ethanol seeking by increasing neuronal activation and reducing oligodendroglial/neuroinflammatory factors in the medial prefrontal cortex.

The therapeutic effects of wheel running (WR) during abstinence on reinstatement of ethanol seeking behaviors in rats that self-administered ethanol only (ethanol drinking, ED) or ED with concurrent chronic intermittent ethanol vapor experience (CIE-ED) were investigated. Neuronal activation as well as oligodendroglial and neuroinflammatory factors were measured in the medial prefrontal cortex (mPFC) tissue to determine cellular correlates associated with enhanced ethanol seeking. CIE-ED rats demonstrated escalated and unregulated intake of ethanol and maintained higher drinking than ED rats during abstinence. CIE-ED rats were more resistant to extinction from ethanol self-administration, however, demonstrated similar ethanol seeking triggered by ethanol contextual cues compared to ED rats. Enhanced seeking was associated with reduced neuronal activation, and increased number of myelinating oligodendrocyte progenitors and PECAM-1 expression in the mPFC, indicating enhanced oligodendroglial and neuroinflammatory response during abstinence. WR during abstinence enhanced self-administration in ED rats, indicating a deprivation effect. WR reduced reinstatement of ethanol seeking in CIE-ED and ED rats, indicating protection against relapse. The reduced ethanol seeking was associated with enhanced neuronal activation, reduced number of myelinating oligodendrocyte progenitors, and reduced PECAM-1 expression. The current findings demonstrate a protective role of WR during abstinence in reducing ethanol seeking triggered by ethanol contextual cues and establish a role for oligodendroglia-neuroinflammatory response in ethanol seeking. Taken together, enhanced oligodendroglia-neuroinflammatory response during abstinence may contribute to brain trauma in chronic alcohol drinking subjects and be a risk factor for enhanced propensity for alcohol relapse.

Evaluating Exercise as a Therapeutic Intervention for Methamphetamine Addiction-Like Behavior.

The need for effective treatments for addiction and dependence to the illicit stimulant methamphetamine in primary care settings is increasing, yet no effective medications have been FDA approved to reduce dependence [1]. This is partially attributed to the complex and dynamic neurobiology underlying the various stages of addiction [2]. Therapeutic strategies to treat methamphetamine addiction, particularly the relapse stage of addiction, could revolutionize methamphetamine addiction treatment. In this context, preclinical studies demonstrate that voluntary exercise (sustained physical activity) could be used as an intervention to reduce methamphetamine addiction. Therefore, it appears that methamphetamine disrupts normal functioning in the brain and this disruption is prevented or reduced by engaging in exercise. This review discusses animal models of methamphetamine addiction and sustained physical activity and the interactions between exercise and methamphetamine behaviors. The review highlights how methamphetamine and exercise affect neuronal plasticity and neurotoxicity in the adult mammalian striatum, hippocampus, and prefrontal cortex, and presents the emerging mechanisms of exercise in attenuating intake and in preventing relapse to methamphetamine seeking in preclinical models of methamphetamine addiction.