Endometrial thickness assessed by transvaginal ultrasound in transmasculine people taking testosterone compared with cisgender women.

RESEARCH QUESTION: What is the endometrial thickness of endometrium exposed to testosterone in transmasculine people compared with unexposed endometrium in cisgender women as determined by transvaginal ultrasound (TVU)? DESIGN: Single centre, cross-sectional cohort study conducted the Centre of Expertise on Gender Dysphoria in Amsterdam. Between 2013 and 2015, transmasculine people scheduled for gender affirming surgery (GAS) were included in this study after they provided informed consent. They were undergoing gender affirming hormone therapy (testosterone) for at least 1 year. Endometrial thickness (mm) was measured by TVU in transmasculine people, immediately before their GAS while under general anaesthesia. Cisgender control women from the general population underwent the exact same TVU measurements in an outpatient clinical setting on cycle days 2-5. RESULT: Fifty-one transmasculine people and 77 controls were included. The mean duration of testosterone use was 30.2 months (SD 8.8). Endometrial thickness was significantly lower in transmasculine people compared with cisgender women: median 3.9 mm (interquartile range [IQR] 2.8-5.1) and 4.9 mm (IQR 4.0-6.3), respectively (P < 0.001), after correcting for confounding factor (current gonadotrophin releasing hormone agonist use). CONCLUSIONS: Endometrial thickness in transmasculine people exposed to testosterone is significantly lower compared with cisgender women without testosterone exposure. These results suggest an absence of endometrial proliferation by exogenous testosterone.

Anti-Müllerian Hormone Levels in Adolescence in Relation to Long-term Follow-up for Presence of Polycystic Ovary Syndrome.

CONTEXT: Anti-Müllerian hormone (AMH) measured in adolescence as biomarker for prediction of adult polycystic ovary syndrome (PCOS) is doubtful but not substantiated. OBJECTIVE: To investigate whether serum AMH levels and other PCOS-associated features in adolescence can predict the presence of PCOS in adulthood. DESIGN AND SETTING: A long-term follow-up study based on a unique adolescent study on menstrual irregularities performed between 1990 and 1997. PARTICIPANTS AND INTERVENTIONS: AMH was assayed in 271 adolescent girls. Data on PCOS features were combined with AMH levels. In 160 of the 271 (59%) participants, we collected information in adulthood about their menstrual cycle pattern and presence of PCOS (features) by questionnaire 2 decades after the initial study. RESULTS: AMH was higher in adolescent girls with oligomenorrhea compared with girls with regular cycles, median (interquartile range): 4.6 (3.1-7.5) versus 2.6 (1.7-3.8) µg/L (P < 0.001). Women with PCOS in adulthood had a higher median adolescent AMH of 6.0 compared with 2.5 µg/L in the non-PCOS group (P < 0.001). AMH at adolescence showed an area under the receiver operating characteristic curve for PCOS in adulthood of 0.78. In adolescent girls with oligomenorrhea the proportion developing PCOS in adulthood was 22.5% (95% CI, 12.4-37.4) against 5.1% (95% CI, 2.1-12.0) in girls with a regular cycle (P = 0.005). Given adolescent oligomenorrhea, adding high AMH as factor to predict adult PCOS or adult oligomenorrhea was of no value. CONCLUSIONS: Adolescent AMH either alone or adjuvant to adolescent oligomenorrhea does not contribute as prognostic marker for PCOS in adulthood. Therefore, we do not recommend routine its use in clinical practice.

Effects of long-term exogenous testosterone administration on ovarian morphology, determined by transvaginal (3D) ultrasound in female-to-male transsexuals.

STUDY QUESTION: Does long-term exogenous testosterone administration result in polycystic ovarian morphology (PCOM), determined by (3D) transvaginal ultrasound (TVU) in female-to-male transsexuals (FtMs). SUMMARY ANSWER: Long-term exogenous testosterone administration in FtMs does not result in PCOM determined by (3D) TVU. WHAT IS KNOWN ALREADY: The role of androgens in the pathophysiology of polycystic ovary syndrome (PCOS) is still unclear. From animal studies, intra-ovarian androgens have been suggested to disturb folliculogenesis, through a pro-atretic effect on growing follicles. It remains debatable whether exogenous androgens induce PCOM in humans. In the past histomorphologic studies indicated that androgen administration in FtMs could cause PCO-like changes. However, ultrasound morphology is an established criterion for PCOS, TVU data of ovaries after prolonged androgen exposure are lacking. STUDY DESIGN, SIZE, DURATION: Prospective, observational, case-control study, in an academic setting, performed in 2014-2015, including 56 FtMs and 80 controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study population consisted of adult FtMs treated with long-term testosterone, as part of their cross-sex hormone treatment, and scheduled for sex-reassignment surgery (bilateral salpingo-oophorectomy). Prior to the operation, under anaesthetics TVU measurements (3D transvaginal probe 3-9 MHz; HD11, Philips Ultrasound, Inc.) of the ovaries were performed. The control group consisted of females from a general population who underwent the same TVU and analysis. Antral follicle count (AFC) (3D) and ovarian volume (3D) were calculated using specialized software. PCOM was defined as AFC of 12 or more follicles (2-10 mm) in at least one ovary. MAIN RESULTS AND THE ROLE OF CHANCE: Prevalence rates of PCOM were not significantly different in the FtMs compared to controls, determined by (3D) TVU: 32.1% (17/53) versus 30.7% (23/75), P = 0.87. LIMITATIONS, REASONS FOR CAUTION: Testosterone levels in FtMs are supraphysiological, and may not be comparable to the testosterone levels in women with PCOS. However, we applied a unique and ethically acceptable opportunity of exploring the effects of androgens on human ovaries. WIDER IMPLICATIONS OF THE FINDINGS: This first explorative study shows that long-term exogenous testosterone administration in adult women does not seem to induce PCOM determined by TVU. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: The trial was registered at the Dutch Trial Register (www.trialregister.nl), registration number NTR4784.

Embryo Transfer with Controlled Injection Speed to Increase Pregnancy Rates: A Randomized Controlled Trial.

BACKGROUND/AIMS: Catheter injection speed affects depth and placement of the embryo into the uterine cavity and is shown to be highly variable in, and between, subjects in a manually performed embryo transfer. In an effort to standardize the injection speed during embryo transfer, we developed an automated transfer pump: the pump-regulated embryo transfer (PRET) device. In this randomized controlled trial, we aimed to investigate if standardization of the injection speed and pressure with this PRET results in a better controlled positioning of the transferred embryo(s). METHODS: Five hundred ninety-nine in-vitro fertilization/intracytoplasmic sperm injection/frozen-thawed embryo transfer cycles were randomly assigned to the PRET or manual transfer. Positioning of the embryo(s) into the uterine cavity was measured with ultrasound. RESULTS: The PRET device generates a significantly smaller variance of the positioning of the embryo(s) into the uterine cavity. This resulted in an ongoing pregnancy rate of 21% in the PRET versus 17% in the manual (p = 0.22) transfer group; frozen-thawed embryo transfers resulted in 17.5 versus 10.9% (p = 0.097), respectively. CONCLUSION: The PRET results in better controlled positioning of the embryo(s), and it also gives the opportunity to standardize embryo transfer. Whether the PRET may positively influence pregnancy rates, needs to be investigated in a multicenter trial.

Mass spectrometry methods measured androgen and estrogen concentrations during pregnancy and in newborns of mothers with polycystic ovary syndrome.

OBJECTIVE: Little is known about the aetiology of polycystic ovary syndrome (PCOS). Some suggest that elevated maternal androgens during gestation play a causative role. This implies placental passage of androgens during pregnancy. The aim of this study is to compare androgen and estrogen concentrations in maternal serum during pregnancy and in umbilical cord blood, between mothers with PCOS and their offspring compared to controls. DESIGN: Prospective case-control study. METHODS: Maternal blood samples were collected around 20 weeks of gestation and at delivery. Umbilical cord blood was also taken at delivery. Androgens (testosterone (T), androstenedione (ADION), dehydroepiandrostenedione (DHEA)) and estrogens (estrone (E1), estradiol (E2), estriol (E3)) were measured using the liquid chromatography tandem mass spectrometry (LC-MS/MS) methods. RESULTS: At 20 weeks of gestation: T (P=0.019) and ADION (P=0.034) were higher in the PCOS mothers (pregnant with a girl), whereas DHEA, E1, E2, and E3 were not different. Maternal concentration at birth: T (P=0.004) and ADION (P=0.009) were also higher in the subgroup of PCOS mothers that were pregnant with a girl compared to the girl pregnancy controls. DHEA, E1, E2 and E3 were not different. In umbilical cord blood, no differences were found for T, ADION, DHEA, E2, E3, and AMH between the PCOS mothers and the controls respectively. E1 was lower in girls from PCOS mothers (P=0.007). CONCLUSIONS: Despite elevated maternal androgen concentrations during pregnancy in PCOS mothers, offspring showed no signs of elevated androgen concentrations in cord blood at birth using the latest highly specific LC-MS/MS methods.

Mid-pregnancy, perinatal, and neonatal reproductive endocrinology: a prospective cohort study in twins and singleton control subjects.

OBJECTIVE: To answer the questions: Are perinatal reproductive hormone profiles different in case of a twin compared with a singleton pregnancy? Are reproductive endocrine profiles of twin girls influenced by their male co-twin and vice versa? DESIGN: Prospective cohort study from January 2004 to October 2009. SETTING: Not applicable. PATIENT(S): A total of 204 mothers of twins and 248 singleton control subjects, aged >18 years, pregnant with a twin or singleton and no endocrine disease or malignancy. INTERVENTION(S): Blood samples were collected at mid-gestation from the mother and at delivery from the mothers and the umbilical cords. Estrogens, androgens, sex hormone-binding globulin, progesterone, and gonadotropins were measured. MAIN OUTCOME MEASURE(S): Hormonal profiles were compared between singletons and twins, different types of twins, and opposite-sex and same-sex twins. RESULT(S): Estrogen and progesterone concentrations were higher in mothers of twins compared with singletons, but twin babies had lower estrogen and progesterone concentrations at birth. Opposite-sex twin girls did not have higher androgens in cord blood compared with same-sex twin girls. Boys of an opposite-sex twin had lower luteinizing hormone concentrations compared with dizygotic twin boys with a brother as a co-twin. CONCLUSION(S): Children from a twin are not overexposed to sex steroids at the time of birth, despite higher concentrations in their mothers, and girls from opposite sex twins do not show androgenic influences from their male co-twin. The female co-twin may influence the hypothalamic-pituitary-testicular axis of her brother via central inhibition.

Antimüllerian hormone levels decrease in female-to-male transsexuals using testosterone as cross-sex therapy.

OBJECTIVE: To investigate the effect of hormonal androgenic treatment on antimüllerian hormone (AMH) serum levels in female-to-male (FtM) transsexuals. Polycystic ovary syndrome (PCOS) is associated with elevated AMH levels. Some hypothesize that the high AMH level is a consequence of androgen-induced excessive development of small antral follicles. However, this role of androgens is not yet clear. DESIGN: Observational, prospective, cohort study. SETTING: Tertiary academic medical center. PATIENT(S): Twenty-two FtM transsexuals, healthy native females receiving cross-sex hormone therapy/androgenic treatment. INTERVENTION(S): Androgenic treatment with testosterone (T) and an aromatase inhibitor while endogenous hormone secretion was suppressed with the use of a GnRH agonist. MAIN OUTCOME MEASURE(S): Hormone concentrations were measured before and after androgenic treatment (administration of T and aromatase inhibitor). Measured hormones: AMH, inhibin B, T, androstenedione, DHEAS, E2, SHBG, LH, and FSH. RESULT(S): AMH concentrations were significantly lower after androgenic treatment (4.4 ± 4.4 µg/L vs. 1.4 ± 2.1 µg/L). Androgenic treatment resulted in a strong suppression of AMH secretion over a relative short period of 16 weeks. CONCLUSION(S): Our data underscore the likely important role of androgens in the dynamics of folliculogenesis. It challenges the idea that androgens induce high AMH levels, which is gaining more interest nowadays as an important particular PCOS feature. This strong decline furthermore indicates that AMH must be interpreted in the context of other reproductive endocrine conditions. CLINICAL TRIAL REGISTRATION NUMBER: NTR2493.