Loss of Mafb and Maf distorts myeloid cell ratios and disrupts fetal mouse testis vascularization and organogenesis†.

Testis differentiation is initiated when Sry in pre-Sertoli cells directs the gonad toward a male-specific fate. Sertoli cells are essential for testis development, but cell types within the interstitial compartment, such as immune and endothelial cells, are also critical for organ formation. Our previous work implicated macrophages in fetal testis morphogenesis, but little is known about genes underlying immune cell development during organogenesis. Here, we examine the role of the immune-associated genes Mafb and Maf in mouse fetal gonad development, and we demonstrate that deletion of these genes leads to aberrant hematopoiesis manifested by supernumerary gonadal monocytes. Mafb; Maf double knockout embryos underwent initial gonadal sex determination normally, but exhibited testicular hypervascularization, testis cord formation defects, Leydig cell deficit, and a reduced number of germ cells. In general, Mafb and Maf alone were dispensable for gonad development; however, when both genes were deleted, we observed significant defects in testicular morphogenesis, indicating that Mafb and Maf work redundantly during testis differentiation. These results demonstrate previously unappreciated roles for Mafb and Maf in immune and vascular development and highlight the importance of interstitial cells in gonadal differentiation.

Young Adult Males' Perspectives of Male Hormonal Contraception.

OBJECTIVE: To evaluate the willingness of young adult males to use male hormonal contraception and to determine the most desirable formulation. METHODS: An institutional review board-approved survey measuring the willingness to use MHC was dispersed to two distinct populations: University of Cincinnati postgraduate programs and Cincinnati Health Department clinics. Questions on the survey allowed for the collection of demographic characteristics, as well as the preferred method of MHC, and concerns regarding potential adverse effects. This survey was directed at young adult males; therefore, only male participants who were 18 to 35 years old were included for analysis. Results were reported as frequencies in each group and χ2 analyses were performed to compare groups, with a P < 0.05 considered significant. RESULTS: Of 162 total survey participants, 45% would use MHC, whereas 30.9% were unsure and 23.5% would not use MHC. Overall, the University of Cincinnati survey population was more likely to be interested in using MHC than the Cincinnati Health Department population (P < 0.05). In both populations, most were interested in using the injectable form. Cited concerns deterring participants from using MHC were different between these two populations, with University of Cincinnati participants more frequently expressing concerns about possible failure of the contraceptive method, whereas Cincinnati Health Department participants had concerns about potential adverse effects (P < 0.001). CONCLUSIONS: There is significant interest among young adult males in using various forms of MHC, especially in injectable form. Differences in views of MHC were seen in two distinct male populations. Specifically, males who achieved a higher level of education, were employed, or in a relationship were found to more frequently be willing to use MHC. With further research and funding, MHC may serve as a significant way to decrease unintended pregnancies in the future.

Postponing Childbearing and Fertility Preservation in Young Professional Women.

OBJECTIVES: To evaluate young women's awareness of ovarian reserve testing and oocyte cryopreservation (OC) and assess how testing ovarian reserve may affect the desire for fertility preservation. METHODS: Three questionnaire-based observational studies were conducted among female students/young professionals 20 years of age and older. The third survey was completed after participants were offered anti-Mullerian hormone (AMH) testing. The main outcomes measured included awareness that OC is available, interest in pursuing fertility preservation, and whether interest would change based on knowledge of declining fertility. RESULTS: The first tier of the study included a survey of a total of 337 women. The majority of female subjects were aware of OC (92.1%). Approximately 38.5% of the women responded that they would consider OC for future fertility purposes. This percentage increased to 60.3% if one was aware her fertility was declining. The second tier of the study included 42 resident/fellow physicians who were offered AMH testing. A survey was completed before and after testing was completed. Approximately 12% of participants stated that their AMH level altered their anticipated age of childbearing, whereas 24% would consider cryopreservation based on their results. The most common concern regarding OC was the cost. CONCLUSIONS: Women should be counseled regarding reproductive aging and options for fertility preservation. Offering ovarian reserve testing and making OC more affordable may increase the number of women who undergo elective OC.

Influence of paternal age on perinatal outcomes.

BACKGROUND: There is an increasing trend to delay childbearing to advanced parental age. Increased risks of advanced maternal age and assisted reproductive technologies are widely accepted. There are limited data regarding advanced paternal age. To adequately counsel patients on risk, more research regarding advanced paternal age is necessary. OBJECTIVE: We sought to determine the influence of paternal age on perinatal outcomes, and to assess whether this influence differs between pregnancies achieved spontaneously and those achieved with assisted reproductive technology. STUDY DESIGN: A population-based retrospective cohort study of all live births in Ohio from 2006 through 2012 was completed. Data were evaluated to determine if advanced paternal age is associated with an increased risk of adverse outcomes in pregnancies. The analysis was stratified by status of utilization of assisted reproductive technology. Generalized linear regression models assessed the association of paternal age on pregnancy complications in assisted reproductive technology and spontaneously conceived pregnancies, after adjusting for maternal age, race, multifetal gestation, and Medicaid status, using Stata software (Stata, Release 12; StataCorp, College Station, TX). RESULTS: Paternal age was documented in 82.2% of 1,034,552 live births in Ohio during the 7-year study period. Paternal age ranged from 12-87 years, with a median of 30 (interquartile range, 26-35) years. Maternal age ranged from 11-62 years, with a median of 27 (interquartile range, 22-31) years. The use of assisted reproductive technology in live births increased as paternal age increased: 0.1% <30 years vs 2.5% >60 years, P < .001. After accounting for maternal age and other confounding risk factors, increased paternal age was not associated with a significant increase in the rate of preeclampsia, preterm birth, fetal growth restriction, congenital anomaly, genetic disorder, or neonatal intensive care unit admission. The influence of paternal age on pregnancy outcomes was similar in pregnancies achieved with and without assisted reproductive technology. CONCLUSION: Older paternal age does not appear to pose an independent risk of adverse perinatal outcomes, in pregnancies achieved either with or without assisted reproductive technology. However, small effect sizes such as very small risk increases or decreases may not be detectable despite the large sample size in this study of >830,000 births.

The Effect of Baseline Ovarian Cyst on Pregnancy Outcomes in Ovulation Induction/Intrauterine Insemination Cycles.

Objective: To determine the effects of a baseline ovarian cyst on ovulation induction/intrauterine insemination (OI/IUI) cycle outcomes. Methods: A retrospective cohort analysis of 270 patients and 461 OI/IUI cycles performed between 2011 and 2021 was performed. The exposure variable was a simple appearing ovarian cyst diagnosed at baseline ultrasound measuring ≥10 mm with an estradiol level <75 ng/mL. The primary outcome analyzed was an ultrasound-confirmed intrauterine pregnancy. Secondary outcomes included positive pregnancy test and live birth. Summary data were presented with percentages, mean (standard deviation), or median (interquartile range). Comparisons of dichotomous variables were performed with the chi-square test, and continuous variables were compared using t-test. Regression analysis was performed using a general linear model. p-Values <0.05 were considered statistically significant. Results: The clinical pregnancy rate was nominally higher in the group without a cyst present at baseline ultrasound compared with those cycles with a simple cyst present, but the difference was not statistically significant (45/300 [15%] vs. 15/161 [9.3%], risk ratio [RR] 0.63 [0.36, 1.1]). After adjusting for BMI ≥30 and age ≥35, there remained no significant difference in clinical pregnancy rate (adjusted RR 0.65 [0.37, 1.1]). Conclusion: Given the present data, it is reasonable to proceed with IUI in the case of a baseline simple ovarian cyst. However, this finding may have an impact on clinical pregnancy outcomes in OI/IUI, and further research on the topic is warranted. Although this study was underpowered with fewer cycles than needed to demonstrate a significant difference, the point estimate suggests that the difference in clinical pregnancy rate could be ∼35%.

Uterine fibroid cell cytoskeletal organization is affected by altered G protein-coupled estrogen receptor-1 and phosphatidylinositol 3-kinase signaling.

OBJECTIVE: To determine whether cyclic strain affects fibroid cell cytoskeletal organization, proliferation, and collagen synthesis differently than myometrial cells. DESIGN: A basic science study using primary cultures of patient-matched myometrial and fibroid cells. SETTING: Academic laboratory. PATIENT(S): Premenopausal women undergoing myomectomy or hysterectomy for the treatment of symptomatic uterine fibroids. INTERVENTION(S): Application of uniaxial strain patterns mimicking periovulation, menses, or dysmenorrhea using the Flexcell tension system or static control. Secondarily, inhibition of G protein-coupled estrogen receptor-1 and phosphatidylinositol 3-kinase. MAIN OUTCOME MEASURE(S): Cell alignment, cell number, and collagen content. RESULT(S): Menses-strained cells demonstrated the most variation in cell alignment, cell proliferation, and procollagen content between myometrial and fibroid cells. Procollagen content decreased in myometrial cells with increasing strain amplitude and decreasing frequency. G protein-coupled estrogen receptor-1 inhibition decreases cellular alignment in the presence of strain. CONCLUSION(S): Mechanotransduction affecting cytoskeletal arrangement through the G protein-coupled estrogen receptor-1-phosphatidylinositol 3-kinase pathway is altered in fibroid cells. These results highlight the importance of incorporating mechanical stimulation into the in vitro study of fibroid pathology.

Women's preferences for a new contraceptive under development: an exploratory study.

Objective: Currently available contraceptive methods do not meet the needs of all users. We sought to explore preferences of potential end-users regarding an on-demand, non-hormonal female contraceptive currently under development, using a web-based survey. Study design: We recruited respondents for an exploratory survey via web link on Amazon Mechanical Turk (MTurk). Individuals were eligible if they were 18-44 years of age, identified as cis-gender female, were English-speaking, not pregnant, and had used barrier contraception previously. Respondents provided demographic characteristics and a basic reproductive history. We then provided a brief description of the potential contraceptive. Respondents were asked about their interest in the proposed contraceptive and preferences for method attributes. Results: A total of 500 respondents completed the survey. Three-quarters of respondents were <35 years of age and 48.2% were currently using a barrier contraceptive method. Three-fourths of respondents (73.8%) expressed interest in using the contraceptive under development. The majority wanted the method to be small (≤2 inches), rod-shaped, and low cost (<$5 per use). More than half (59.4%) said it was important to be able to use the method without partners' knowledge. The most reported potential concerns were vaginal irritation (51.6%) and lack of effectiveness (46.4%). Sixty percent of respondents were confident they could use the method correctly. Discussion: Available contraceptive methods lack attributes preferred by some users. Development of new contraceptives frequently does not involve end-user input early in the development process. Individuals in this sample displayed interest in the proposed contraceptive and expressed preferences that can inform the further development of this method.

Minimal Stimulation Using Gonadotropin-Releasing Hormone Antagonist is Associated with Higher Live Birth Rates: A National Study of 13,050 Cycles.

Background: The optimal protocol for minimal stimulation in vitro fertilization (IVF) has yet to be established. This study aims to determine if the use of gonadotropin-releasing hormone (GnRH) antagonist during minimal stimulation improves outcomes. Materials and Methods: All cycles designated as minimal stimulation from 2014 to 2016 from the Society for Assisted Reproductive Technology Clinic Online Reporting System were identified. Cycles in which GnRH antagonist was administered (n = 5984) were compared to those that did not receive it (n = 7066). Wilcoxon's rank-sum test and chi-square test were used to analyze continuous and categorical variables. Results: A total of 6750 patients undergoing 13,050 cycles were included. GnRH antagonist use was associated with a significantly higher total gonadotropin dosage (median 975.0 [interquartile range, IQR, 600.0, 1575.0] vs. median 660.0 [IQR 375.0, 975.0], p < 0.001), lower cycle cancelation rate (11.3% vs. 13.6%, p < 0.001; OR 1.24, 95% CI 1.12-1.38, p < 0.001), and higher live birth rate (4.3% vs. 2.1%, p < 0.001; OR 0.47, 95% CI 0.39-0.58, p < 0.001). GnRH antagonist use was associated with a significantly higher live birth rate in women ≥35 years of age (2.7% vs. 0.9%, p < 0.001; OR 0.34, 95% CI 0.25-0.47, p < 0.001) and antimullerian hormone <1 (4.9% vs. 2.6%, p = 0.004; OR 0.52, 95% CI 0.33-0.81, p = 0.004). Conclusion: The use of GnRH antagonist suppression during minimal stimulation IVF is associated with an improved live birth rate, especially in older women and in women with diminished ovarian reserve. Although GnRH antagonist use may increase costs, it significantly decreases cancelation rate, increases number of embryos cryopreserved, and should be encouraged for minimal stimulation IVF.