Stewart, Elizabeth A.

Background With improvements in in vitro culture techniques, there has been a steady shift in practice to transfer in vitro fertilisation (IVF) embryos at the blastocyst-stage to increase pregnancy rates per embryo transfer (ET) and reduce the risk of multiple pregnancy. In patients with fewer embryos (≤5 zygotes), fresh cleavage-stage ET is still commonly performed to reduce the risk of cycle cancellation if no embryo survives to the blastocyst-stage in vitro. However, evidence for improved outcomes with cleavage-stage embryo transfer in this subgroup of patients is lacking. We will compare blastocyst-stage to cleavage-stage ET with regard to cumulative live birth rates (CLBR) per oocyte retrieval and other patient-centred cycle outcomes in patients with ≤5 zygotes. Methods and analysis Multicentre, randomised pragmatic comparative effectiveness trial with superiority design comparing blastocyst-stage to cleavage-stage ET in patients with ≤5 zygotes. This trial will enrol and randomise 1126 women aged 18–44 undergoing IVF to either fresh cleavage-stage or blastocyst-stage ET at eleven IVF centres. Surplus embryos will be vitrified at the blastocyst-stage. The primary outcome is the CLBR per oocyte retrieval. Secondary outcomes include: multiple pregnancy, pregnancy loss <20 weeks and cycle cancellation. Exploratory outcomes include: live birth per fresh ET, ectopic pregnancy, time to pregnancy, stillbirth, preterm birth, financial burden, patient distress and facilitators and barriers for patient involvement and implementation. All primary analyses will be conducted according to the intent-to-treat principle. We also will report per-protocol analyses as a sensitivity analysis. A multidisciplinary stakeholder team, including a 5-patient stakeholder panel, will participate in study design, conduct and oversight. Ethics and dissemination The Institutional Review Board at Beth Israel Deaconess Medical Center (BIDMC) provides central regulatory oversight. Results will inform timing of embryo transfer in patients with ≤5 zygotes and will be disseminated through academic publications, meeting presentations and communications to advocacy groups and patient participants. Trial registration number NCT06746129 .

Objective: To evaluate the relationship between race and social determinants of health and receipt of hysterectomy versus uterine-preserving fibroid treatment. Methods: A retrospective cohort study using deidentified claims and longitudinal health data from OptumLabs ® Data Warehouse. Patients aged 15–55 years with newly diagnosed fibroids between 2010 and 2023 were included. Menopausal individuals and those with gynecological cancer were excluded. The primary outcome was hysterectomy by any route versus uterine-preserving fibroid surgery within 180 days of fibroid diagnosis. We used logistic regression to assess associations between socioeconomic factors and receipt of hysterectomy after adjusting for pertinent covariates. Results: A total of 73,479 individuals were included; 50,645 received hysterectomy, 22,834 received a uterine-preserving treatment. Race, income, education level, and rurality were independently associated with the probability of hysterectomy. Odds of hysterectomy were lower for all people of color compared with White individuals (Asian odds ratio [OR] 0.61 [95% confidence interval (CI): 0.56–0.66], Black OR: 0.70 [95% CI: 0.67–0.73], and Hispanic OR: 0.90 [95% CI: 0.86–0.95]). Individuals with household income <$40,000, less than high school education, and rural address were more likely to undergo hysterectomy compared with those with income >$124,999 (OR: 1.15, 95% CI: 1.09–1.21), bachelor’s degree or higher (OR: 2.55, 95% CI: 1.78–3.65), and metropolitan address (OR: 1.70, 95% CI: 1.44–2.01). All associations were significant at p < 0.05. Conclusion: People with fewer socioeconomic advantages, such as lower household income, lower educational attainment, and rural address were more likely to receive hysterectomy rather than uterine-preserving fibroid treatment. After controlling for age, surgery year, and socioeconomic factors, people of color were less likely to receive hysterectomy rather than uterine-preserving fibroid treatment.

Objectives: To analyze the association between primary infertility and infertility type with the age of natural menopause. Methods: This is a retrospective cohort study reviewing a subset of women from the Mayo Primary Infertility Cohort (MPIC). The MPIC is a cohort of 1,001 women diagnosed with primary infertility and 1,001 age-matched referent women. In this study, we included all women at risk for natural menopause and further evaluated those who had reported natural menopause in the medical record. We compared the risk of natural menopause using Cox proportional hazard models with infertility status and infertility type as covariates. In those with documented menopause during the study period, the association between primary infertility and early and premature menopause was analyzed with χ 2 testing. We evaluated the association between age at natural menopause, primary infertility status, and infertility type in this group using linear regression. Results: In all, 461 women with primary infertility, with 530 referent individuals, were at risk of natural menopause, and of these, 340 women with infertility and 346 referent women underwent documented natural menopause on review of medical records. Women with primary infertility had an increased risk of natural menopause (hazard ratio: 1.25, 95% CI: 1.06-1.46) and underwent menopause 1 year earlier than referent individuals (β=−1.17, 95% CI: −1.82 to −0.52) after adjustment for body mass index, tobacco use, race, menstrual cycle regularity, and previous contraception use. Women with primary infertility were more likely to undergo early menopause (age 40-45) than referent women (7.6% vs. 3.0%, P =0.01). Compared with referent women, women with endometriosis underwent menopause 2.75 years earlier (95% CI: −4.38 to −1.13, P =0.0009), and women with unexplained infertility underwent menopause 1.45 years earlier (95% CI: −2.26 to −0.64, P =0.0005). Conclusions: Women with primary infertility had an increased risk of early menopause and collectively underwent menopause 1 year earlier than women without a history of primary infertility.

Abstract Objective To compare the long‐term risk of subsequent abdominopelvic surgery in women who underwent hysterectomy with ovarian conservation (H‐OC) versus referent women, and in women who underwent abdominal H‐OC versus vaginal H‐OC. Methods We conducted a population‐based cohort study in Olmsted County, Minnesota, USA including 1573 women who underwent H‐OC for a benign indication at age 18–44 years between January 1, 1980, and December 31, 2002, and 1573 age‐matched (±1 year) referent women who had not undergone hysterectomy or any oophorectomy as of the matching date. For both the H‐OC women and the referent women, we defined the index date as the H‐OC or matching date plus 6 months. The index date served as the starting point for follow‐up. Results Overall, we found an increased risk of subsequent lysis of adhesions in women who underwent H‐OC compared to referent women (hazard ratio [HR], 1.57 [95% confidence interval [CI]: 1.09–2.27]). Women undergoing H‐OC also had an increased risk of subsequent gastrointestinal tract procedures (HR, 1.18 [95% CI: 1.05–1.31]) compared to referent women. When comparing surgical route of H‐OC, we identified an increased risk of subsequent adnexal surgeries in women undergoing abdominal compared with vaginal H‐OC (HR, 1.91 [95% CI: 1.40–2.61]). Conclusion Women who underwent H‐OC have an increased risk of subsequent abdominopelvic surgeries compared to referent women. In addition, women who underwent abdominal H‐OC have an increased risk of subsequent adnexal procedures compared to women who underwent vaginal H‐OC.

Objectives: To determine the risk of developing de novo carpal tunnel syndrome (CTS), arthritis, or rheumatoid arthritis in women who underwent hysterectomy with bilateral ovarian conservation (H-OC) before reaching spontaneous menopause. Methods: We identified 1,573 women undergoing H-OC for a benign indication at age 18 to 44 years between 1980 and 2002 in Olmsted County, Minnesota. Each woman was age-matched (±1 y) to a referent woman who had not undergone hysterectomy or oophorectomy before the matching date (index date). Diagnostic codes for CTS and arthritis were extracted from the Rochester Epidemiology Project medical records-linkage system through 2019. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models and the two cohorts were balanced for 19 chronic conditions and for several potential confounders present at index date. Results: Over a median 25.8-year follow-up, women undergoing H-OC had an increased risk of developing CTS (HR: 1.33; 95% CI: 1.13-1.56) compared with referent women. The risk was similar in strata by age at H-OC and was higher for women with endometriosis and menstrual disorders indications. Women undergoing H-OC also had an increased risk of developing arthritis (HR: 1.34; 95% CI: 1.23-1.47). The risk was similar in strata by age at H-OC and by indication. Rheumatoid arthritis considered separately was also associated with H-OC (HR: 1.55; 95% CI: 1.05-2.30). Conclusions: H-OC was associated with an increased risk of de novo CTS, arthritis (all types), and rheumatoid arthritis. Further studies are needed to confirm these associations and to explore potential biological mechanisms.

Uterine leiomyomas are noncancerous smooth muscle neoplasms that occur in up to 70% of women and the single most common cause of hysterectomy. There is a variety of treatments available for uterine leiomyomas, including medications, uterine artery embolization, myomectomy, and hysterectomy but surgical treatments predominate. Medical optimization of anemia is often required prior to surgical treatment secondary to heavy menstrual bleeding and resultant iron deficiency anemia from chronic blood loss. While iron and multivitamins are critical to increase hemoglobin, pharmacologic therapy to suppress menstrual bleeding is often needed. First line therapy is typically a trial of combined oral contraceptive pills (OCPs); however, this may not be effective in all patients. Parenteral administration of long-acting GnRH agonists is often used as a second line treatment; however, these agents can lead to an initial “flare” effect precipitating a heavy bleed during the agonist phase which can be problematic in such patients. An alternative course of action is the use of oral GnRH antagonist combination therapy (OGAC) with estradiol and norethindrone, an option approved in both the United States and the European Union for long-term treatment of leiomyoma-related heavy menstrual bleeding. To demonstrate the clinical utility of OGAC therapy in the preoperative setting, we report a successful patient outcome and review relevant literature.

Abstract The impact of early-life traumatic experiences on late-life morbidity remains partly unknown. We tested the hypothesis that adverse childhood experiences (ACE) and specifically abuse (physical, verbal or emotional, or sexual) experienced during childhood or early adulthood are associated with a higher rate of accumulation of multi-morbidity in women. Here we show strong evidence in support of the hypothesis. We studied 1,026 women aged 21–45 years randomly selected from the general population in Olmsted County, Minnesota and used the Rochester Epidemiology Project medical records-linkage system to measure the rate of development of 18 chronic conditions. The women had a median age of 41 years at inclusion in the study and were followed historically for a median of 21 years. Women with an ACE score ≥ 2 had higher incidence of 10 of the 18 chronic conditions considered separately and an accelerated accumulation of multi-morbidity measured as a score compared to women with ACE score 0. In addition, women exposed specifically to abuse in childhood or early adulthood had accelerated accumulation of multi-morbidity. We excluded the possible confounding effect of socioeconomic status and explored a series of possible mediation events or characteristics. We discuss several possible biological and social or behavioral mechanisms underlying these associations.

Abstract Introduction Microdissection testicular sperm extraction (microTESE) is performed in men with nonobstructive azoospermia who desire sperm retrieval for use in IVF. This procedure can be performed in the operating room or in the clinic with local analgesic. Objective To report office-based microTESE sperm retrieval, fertilization, and livebirth rates. Methods A review was conducted of all patients who underwent office-based microTESE for nonobstructive azoospermia with a partner that who underwent concurrent oocyte retrieval for an intended in-vitro fertilization (IVF) intracytoplasmic injection (ICSI) cycle 2022-2024. All male partners underwent Y chromosome microdeletion testing, karyotype analysis, and hormonal testing preoperatively. Patients with a diagnosis of hypogonadism were offered medical therapy and those diagnosed with a varicocele were offered varicocelectomy prior to microTESE. Office-based microTESE was performed using a surgical operating microscope, spermatic cord block, and oral anxiolytic. Female partners underwent oocyte retrieval with oocyte cryopreservation prior to microTESE. Oocyte warming and ICSI was performed only following the collection of motile sperm from the fresh microTESE samples. Relevant demographic and clinical data were collected for patients and their partners. Descriptive data analysis was performed and reported as mean ± standard deviation. Results Ten patients underwent 11 office-based microTESE procedures. One patient had repeat microTESE following an unsuccessful IVF/ICSI cycle. Overall sperm retrieval rate was 70% for first time microTESE with mean search time 197.2 ± 96.5 min. Amongst couples with successful sperm retrieval, normal fertilization rate was 42%. Early cleavage arrest was seen in 84% of normally fertilized oocytes with a 16% blastocyst rate. Embryo development arrested entirely in two couples, while the remaining five couples had at least one blastocyst on day 5 and underwent embryo transfer. Of these, four resulted in a clinical pregnancy (36%). Three couples had a successful live birth and one has an ongoing pregnancy with ultrasound-confirmed fetal heartbeat. Conclusions Our small series demonstrates high sperm retrieval rates from office-based microTESE. Fertilization rates, clinical pregnancies and live birth rates are comparable with those reported in the literature. Given the financial cost associated with microTESE and IVF/ICSI for nonobstructive azoospermia patients, office-based microTESE may be a solution to make the process more financially accessible for couples. Disclosure No.