Does mRNA SARS-CoV-2 vaccine detrimentally affect male fertility, as reflected by semen analysis?

RESEARCH QUESTION: Does Pfizer's coronavirus disease 2019 (COVID-19) vaccination detrimentally affect semen analysis parameters? DESIGN: A prospective cohort study was conducted at a single large tertiary centre in Israel between February and March of 2021. Semen samples from 75 fertile men were analysed 1-2 months following their second dose of Pfizer's COVID-19 vaccine. The semen parameters were compared with the World Health Organization (WHO) reference ranges. The primary outcome was the percentage of abnormal semen parameters in those who were vaccinated, i.e. the rates of oligozoospermia, reduced percentage of motile spermatozoa and abnormal sperm morphology. RESULTS: The interval from the time of the second vaccination to the date of participation was on average 37 days, with most subjects describing either mild or no side effects after the first or second dose. The mean sperm concentration was 63.2 ± 33.6 â€¯×  106/ml, with only a single participant (1.3%) with a sperm count of 12.5 â€¯×  106/ml, considered by the WHO to be oligozoospermic. The mean sperm motility percentage was 64.5 ± 16.7%, with only a single man (1.3%) displaying reduced motility. No notable morphological abnormalities were observed. This constituted a lower percentage of abnormal semen parameters compared with the 5% rates reported in fertile men by the WHO. CONCLUSIONS: The semen parameters following COVID-19 vaccination were predominantly within the normal reference ranges as set by the WHO and do not reflect any causative detrimental effect from COVID-19 vaccination. The results strengthen the notion that the Pfizer's severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine is safe and should be recommended to men wishing to conceive.

Why fertility preservation rates of transgender men are much lower than those of transgender women.

RESEARCH QUESTION: What are the fertility preservation rates of transgender women and transgender men, and what are the factors that affect their decision-making? DESIGN: This prospective study included 97 transgender women and 91 transgender men referred to the Gender Clinic of the study medical centre's Endocrinology Institute and to the Gan Meir Community Health Care Centre. The responders completed a 28-item questionnaire during 2018. RESULTS: Most of the transgender women and transgender men wished to parent a child (67.4% and 61.9%, respectively, P = 0.447), but only 40.4% of the transgender women and 5.8% of the transgender men used fertility preservation (P < 0.001). The main reasons for not pursuing fertility preservation were unwillingness to postpone gender-affirming treatment (58.8% and 74.0%, respectively, P = 0.076), preference to adopt a child (58.8% and 60.9%, respectively, P = 0.818) and cost (44.9% and 60.9%, respectively, P = 0.086). Factors related to the fertility preservation process itself were specifically chosen by transgender men compared with transgender women as the reason for not pursuing this treatment, including distress caused by the fertility preservation technique (60.3% versus 29.3%, respectively, P = 0.006), fear of gender dysphoria caused by hormonal treatment (63.5% versus 28.3%, P = 0.002) and concern over the attitude of medical staff (44% versus 19%, P = 0.027). CONCLUSIONS: Fertility preservation rates were considerably lower among transgender men than transgender women, strongly related to the fertility preservation process itself. Finding ways to overcome the obstacles confronted by transgender individuals, especially transgender men, will enhance their future biological parenting.

Diagnostic accuracy of random urinary protein-to-creatinine ratio for proteinuria in patients with suspected pre-eclampsia.

PURPOSE: To evaluate the correlation between urine protein/creatinine ratio (UPCR) and proteinuria in a 24-h urine collection and to calculate the predicative accuracy of different cutoffs of UPCR for the diagnosis of proteinuria. METHODS: A retrospective cohort study including women who admitted for the evaluation for suspected preeclampsia (PET) beyond 20 weeks of gestation in a single tertiary center. Both UPCR test and quantification of proteinuria using 24-h urine collection were obtained during their index hospitalization no more than 48 h apart. Women with pre-existing diabetes mellitus, known renal disease or proteinuria prior to pregnancy or chronic hypertension were excluded. Predictive accuracy of UPCR for several cutoffs of proteinuria was evaluated. Multivariate logistic regression analysis was used to assess diagnostic accuracy of UPCR in sub-populations according to obstetrical characteristics. RESULTS: Overall 463 patients were included. Of them 316 (68.3%) have 24-h urine protein collection of ≥ 300 mg/day. Mean gestational age at evaluation was 34.0 ± 3.4 weeks. Median (and interquartile range) time interval between UPCR and 24-h urine collection was 1.8 (1.6-1.9) days. Sensitivity and specificity of UPCR of 0.3 for predicting proteinuria ≥ 300 mg/day were 90.1% and 63.3%, respectively. The corresponding values for difference proteinuria cutoffs: ≥ 1000 mg/day and 5000 mg/day were 98.4, 100% and 29.1, 36.0%, respectively. The optimal UPCR thresholds for 24-h urine protein collection of ≥ 300 mg/day, ≥ 1000 mg/day and 5000 mg/day were 0.31, 0.70 and 2.49, respectively. The predictive accuracy of UPCR > 0.30 in predicting proteinuria was unaffected by demographic and obstetrical characteristics as maternal age, pre-pregnancy BMI, gestational age at examination, creatinine levels or by multiple gestation [adjusted OR 18.27 (95% CI 9.97-33.47)]. CONCLUSION: UPCR was strongly correlated with various cutoffs of proteinuria obtained by 24-h urine collection. UPCR cutoff varied depending on the specific measured outcome. This correlation was not affected by gestational age at examination.

Long term safety of controlled ovarian stimulation for fertility preservation prior to chemotherapy treatment in breast cancer patients.

OBJECTIVE: To evaluate the long-term safety of controlled ovarian stimulation for fertility preservation prior to breast cancer chemotherapy treatment DESIGN: Retrospective observational cohort SUBJECTS: 213 women aged 18-43 years with newly diagnosed stage I-III breast cancer treated with systemic chemotherapy during 2015-2019. Of those, 74 underwent controlled ovarian stimulation for fertility preservation recipients and 141 did not (controls). EXPOSURE: Controlled ovarian stimulation for fertility preservation MAIN OUTCOME MEASURES: Invasive disease-free survival, calculated from the time of surgery to the time of detection of breast cancer recurrence or death, whichever came first. RESULTS: At diagnosis, fertility preservation recipients were significantly younger than controls (32.7 vs 38.5 years), were less likely to be partnered (44.4% vs 90.1%) or parous (38.9% vs 95%) and were more likely to harbor a BRCA germline mutation (36.5% vs 14.2%). Disease characteristics and treatment modalities were comparable between groups, apart from tumor staging, with maximal tumor diameter being over 5 cm in 22.2% of fertility preservation recipients as opposed to 5.7% of controls (P<0.05). Mean follow-up was 60.9 and 65.4 months for fertility preservation recipients and controls, respectively. 5-year-invasive disease free survival was 80% for fertility preservation recipients and 86% for controls (p=0.20). In a multivariate analysis adjusted for statistically significant covariates, invasive disease free survival remained similar between the groups (Hazards Ratio (HR), 0.86, 95CI 0.4-1.87, p = 0.71). Invasive disease free survival rates were not statistically different in clinically relevant subgroups including patients receiving neoadjuvant chemotherapy (HR 1.57, CI 95 0.62-3.99, p=0.34), and those co-treated with tamoxifen during stimulation due to an ER-positive disease (HR 1.66, 95CI 0.67-3.49, p=0.23). CONCLUSIONS: Fertility preservation with controlled ovarian stimulation for patients with breast cancer was not found to impair long-term oncologic outcomes, including in emerging clinically relevant subgroups.

Risk-reducing salpingo-oophorectomy and breast cancer incidence among Jewish BRCA1/BRCA2-mutation carriers-an Israeli matched-pair study.

OBJECTIVE: To study the association of risk-reducing bilateral salpingo-oophorectomy (RRBSO) and breast cancer risk among BRCA pathogenic sequence variants (PSV). METHODS: Jewish Israeli BRCA carriers who underwent RRBSO were matched with those who did not-by the mutated gene and year of birth (±1 year). Breast cancer rates were compared. RESULTS: Overall, 127 pairs met the inclusion criteria, 79 (60.6%) pairs harbored BRCA1 PSV and 50 (39.4%) pairs harbored BRCA2 PSV. Median follow up was 8.7 years (interquartile range 4.6-16.1 years). Breast cancer rate for all BRCA carriers combined was not affected by RRBSO (RRBSO 21 [16.5%] versus no RRBSO 31 [24.4%], hazard ratio [HR] for breast cancer 0.61, 95% confidence interval [CI] 0.33-1.14, P = 0.127). No association between RRBSO and breast cancer incidence was noted among BRCA1 PSV carriers. In BRCA2 PSV carriers, RRBSO was associated with a decreased overall breast cancer incidence (HR 0.20, 95% CI 0.44-0.91, P = 0.038), as well as after 5, 10, 15, and 20 years. Hormone replacement therapy was used by 62 PSV carriers, 52 in the RRBSO group and 10 in the no-RRBSO group and did not affect breast cancer risk (P = 0.463). CONCLUSION: RRBSO is associated with breast cancer risk reduction in Jewish Israeli BRCA2 PSV carriers. Risk-reducing bilateral salpingo-oophorectomy was associated with breast cancer risk reduction in Jewish Israeli BRCA2 pathogenic sequence variant carriers.

Transgender men's preferences when choosing obstetricians and gynecologists.

BACKGROUND: Transgender men are a marginalized population with unique health care needs. However, their usage of health services is low because of considerable discrimination. A major factor in their avoidance is patient-provider interactions. METHODS: This cross-sectional study included 102 transgender men who anonymously completed a 55-item questionnaire in clinic, between 10/2017 and 01/2019. In addition, 92 transgender women filled out the part about family physician's preferences. We examined which characteristics transgender men prefer in their obstetricians/gynecologists in order to promote their usage of healthcare services. RESULTS: A small majority of the transgender men (54.1%) had no gender preference for their obstetrician/gynecologist, while 42.9% preferred a female obstetrician/gynecologist and 3.1% preferred a male obstetrician/gynecologist. Most transgender men with a same-gender preference preferred female obstetricians/gynecologists for both invasive procedures (e.g., pelvic examination, 97.4%) and non-invasive procedures (e.g., cesarean section, 60%). The reasons for preferences regarding invasive procedures were feeling comfortable, embarrassment and feeling that female obstetricians/gynecologists are gentler. Transgender men who preferred female obstetricians/gynecologists ranked ability (90.5%), sexual tolerance (92.9%) and gender identity tolerance (90.5%) as the top three desirable qualities of obstetricians/gynecologists, while the responders who did not prefer female ranked ability (94.6%), experience (92.9%) and knowledge (92.9%) as the top three qualities. Transgender men with female preferences considered female obstetricians/gynecologists to be more accepting of gender identity compared to the responders that did not prefer females (47.5% vs. 9.1%, P < .001).. CONCLUSION: A small majority of the transgender men exhibited no gender preference when choosing an obstetrician/gynecologist, although 42.9% preferred females. The latter choice was associated with the assumption that female obstetricians/gynecologists are more tolerant towards their transgender men patients. Educating the medical staff about their special needs and establishing dedicated SGM centers staffed with high percentages of female healthcare providers are highly recommended.

Fertility treatments and breast cancer risk in Jewish Israeli BRCA mutation carriers.

OBJECTIVE: To determine whether fertility treatments impact the risk of breast cancer in Jewish Israeli BRCA1/2 mutation carriers. DESIGN: Historical cohort study. SETTING: University-affiliated tertiary medical center. PATIENT(S): A total of 1,824 Jewish Israeli BRCA1/2 mutation carriers from a single center were stratified into 1,492 (81.8%) carriers who were not treated for infertility and 332 (18.2%) carriers who underwent fertility treatment with clomiphene citrate (n = 134), gonadotropin (n = 119), in vitro fertilization (n = 183), or a combination of treatments (n = 89). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Hazard ratios (HR) and 95% confidence intervals (CI) for the association of breast cancer with fertility treatment and other hormonal and reproductive variables. RESULT(S): Breast cancer was diagnosed in 687 BRCA1/2 mutation carriers. Multivariate analysis, either of the whole group or stratified by each gene, showed no association between fertility treatment and breast cancer risk, regardless of the type of treatment (clomiphene citrate: HR 0.77, 95% CI 0.49-1.19; gonadotropin: HR 0.54, 95% CI 0.28-1.01; in vitro fertilization: HR 0.65, 95% CI 0.39-1.08; and combined treatments: HR 1.23, 95% CI 0.49-3.06). An increased breast cancer risk was associated with paternal origin of the mutation (HR 1.43, 95% CI 1.17-1.75) and use of oral contraceptives for >5 years (HR 1.62, 95% CI 1.27-2.06) in both BRCA1 and BRCA2 mutation carriers. Ovarian cancer risk was decreased with the use of any oral contraceptive (HR 0.61; 95% CI 0.46-0.82). CONCLUSION(S): Fertility treatment for BRCA1/2 mutation carriers is not associated with a discernible increase in breast cancer risk.

Fertility treatments and invasive epithelial ovarian cancer risk in Jewish Israeli BRCA1 or BRCA2 mutation carriers.

OBJECTIVE: To determine whether BRCA mutation carriers who undergo fertility treatments are at increased risk of developing invasive epithelial ovarian cancer (IEOC). DESIGN: Historical cohort study. SETTING: Tertiary university-affiliated medical center and the National Cancer Registry. PATIENT(S): A total of 1,073 Jewish Israeli BRCA mutation carriers diagnosed in a single institution between 1995 and 2013, including 164 carriers (15.2%) who had fertility treatments that included clomiphene citrate (n = 82), gonadotropin (n = 69), in vitro fertilization (IVF) (n = 66), or a combination (n = 50), and 909 carriers not treated for infertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Odds ratios (OR) and 95% confidence intervals (CI) for IEOC association with fertility treatments and other hormone and reproductive variables. RESULT(S): In 175 (16.3%) mutation carriers, IEOC was diagnosed; 139 women carried BRCA1, 33 carried BRCA2, and 3 had unknown mutations. Fertility treatments were not associated with IEOC risk (age-adjusted OR 0.63; 95% CI, 0.38-1.05) regardless of treatment type (with clomiphene citrate, OR 0.87; 95% CI, 0.46-1.63; with gonadotropin, OR 0.59; 95% CI, 0.26-1.31; with IVF, OR 1.08, 95% CI, 0.57-2.06). Multivariate analysis indicated an increased risk of IEOC with hormone-replacement therapy (OR 2.22; 95% CI, 1.33-3.69) and a reduced risk with oral contraceptives (OR 0.19; 95% CI, 0.13-0.28) in both BRCA1 and BRCA2 mutation carriers. Parity was a risk factor for IEOC by univariate but not multivariate analysis. CONCLUSION(S): According to our results, treatments for infertile BRCA mutation carriers should not be contraindicated or viewed as risk modifiers for IEOC. Parity as a risk factor in BRCA mutation carriers warrants further investigation.