Outcomes of oocyte vitrification in trans masculine individuals.

RESEARCH QUESTION: What are the outcomes and experiences of oocyte vitrification treatment in trans masculine individuals (TMI) before and after testosterone use? DESIGN: This retrospective cohort study was conducted at the Amsterdam UMC in the Netherlands between January 2017 and June 2021. The TMI who had completed an oocyte vitrification treatment were consecutively approached for participation. Informed consent was provided by 24 individuals. Participants (n = 7) who initiated testosterone therapy were advised to stop 3 months before stimulation. Demographic characteristics and oocyte vitrification treatment data were retrieved from medical records. Evaluation of the treatment was collected via an online questionnaire. RESULTS: The median age of participants was 22.3 years (interquartile range 21.1-26.0) and mean body mass index was 23.0 kg/m2 (SD 3.2). After ovarian hyperstimulation, a mean of 20 oocytes (SD 7) were retrieved and a mean of 17 oocytes (SD 6) could be vitrified. Aside from a lower cumulative FSH dose, there were no significant differences between the prior testosterone users and testosterone naïve TMI. The overall satisfaction of oocyte vitrification treatment in participants was high. Hormone injections were considered the most strenuous part of treatment by 29% of participants, closely followed by oocyte retrieval (25%). CONCLUSIONS: No difference in response to ovarian stimulation was found for oocyte vitrification treatment between the prior testosterone users and testosterone naïve TMI. The questionnaire identified hormone injections as the most burdensome aspect of oocyte vitrification treatment. This information can be used to improve gender sensitive fertility counselling and fertility treatment strategies.

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.

Gestational surrogacy: results of 10 years of experience in the Netherlands.

RESEARCH QUESTION: What are the reproductive and obstetric outcomes of the gestational surrogacy treatment in the Netherlands? DESIGN: This retrospective cohort study reports all data of gestational surrogacy treatment in the VU University Medical Centre over a period of 10 years. Data was collected from 60 intended parents and 63 gestational carriers, including reproductive and obstetric outcomes. RESULTS: All intended mothers had a medical indication for gestational surrogacy and used autologous oocytes, and semen of the intended father. Ninety-three IVF cycles were initiated in 60 intended mothers, with subsequent 184 single embryo transfers in 63 gestational carriers. This resulted in 35 ongoing singleton pregnancies. At least one live birth was achieved for 55.0% of intended couples. Pregnancy was complicated in 20.6% by a hypertensive disorder. Labour was induced in 52.9%, and the Caesarean section rate was 8.8%. None of the pregnancies was complicated by preterm birth. Postpartum haemorrhage (>500 ml) occurred in 23.5%. CONCLUSIONS: This study shows the effective results of the non-commercial gestational surrogacy programme in the Netherlands, in a multidisciplinary team setting. An increased risk for adverse obstetric outcomes in surrogate mothers is noted for hypertensive disorders and post-partum haemorrhage compared with the incidence in non-surrogacy pregnancies.

Unusual Twinning Resulting in Chimerism: A Systematic Review on Monochorionic Dizygotic Twins.

Traditionally, it is understood that dizygotic (DZ) twins always have a dichorionic placenta. However, with 8% blood chimerism in DZ twins, placental sharing is probably more common than previously has been recognized. In this article, we will review all available cases of monochorionic dizygotic (MCDZ) twins. A total of 31 twins have been described in literature. A monochorionic diamniotic placenta is reported in all cases. Assisted reproductive technology is responsible for the origin of the pregnancy in 82.1% of the cases. In 15.4% of the sex-discordant twins, a genital anomaly was reported in one of the twins. Chimerism is demonstrable in 90.3% of the twins, leading to various diagnostic difficulties. As this review shows that most MCDZ twins are discovered by accident, it can be argued that it is far more common than has been assumed until now. However, the prevalence is still unclear. Awareness of MCDZ twinning is important, with subsequently correct medical strategies. Similarly, the resulting (blood) chimerism is essential to consider in diagnostic procedures, pre- and postnatally. More research on the effect of placental transfusion between sex-discordant twins is required.

One-third of amenorrheic transmasculine people on testosterone ovulate.

Transmasculine people usually reach amenorrhea within 6 months of adequate testosterone treatment. It is often assumed that no ovulation occurs during amenorrhea. However, in this study, we report recent ovulatory activity in amenorrheic transmasculine people on testosterone therapy at gender-affirming oophorectomy. Histological signs of recent ovulatory activity, including the presence of ovulatory follicles, corpus luteum, and corpus albicans, are observed in 17 of 52 individuals (33%). This is not significantly correlated to the duration, testosterone serum levels, or type of testosterone used. These results suggest that amenorrhea does not equal anovulation in transmasculine people on adequate testosterone therapy, emphasizing the importance of contraception for people who engage in sexual activity that can result in pregnancy.

Reproductive Outcomes of Women with Turner Syndrome Undergoing Oocyte Vitrification: A Retrospective Multicenter Cohort Study.

BACKGROUND: Turner syndrome (TS) is accompanied with premature ovarian insufficiency. Oocyte vitrification is an established method to preserve fertility. However, data on the oocyte yield in women with TS who vitrify their oocytes and the return rate to utilize the oocytes are scarce. METHODS: Retrospective multicenter cohort study. Data was collected from medical records of women with TS who started oocyte vitrification between 2010 and 2021. RESULTS: Thirty-three women were included. The median cumulative number of vitrified oocytes was 20 per woman. Complications occurred in 4% of the cycles. Significant correlations were found between the cumulative number of vitrified oocytes and AMH (r = 0.54 and p < 0.01), AFC (r = 0.49 and p < 0.01), percentage of 46,XX cells (r = 0.49 and p < 0.01), and FSH (r = -0.65 and p < 0.01). Spontaneous (n = 8) and IVF (n = 2) pregnancies occurred in 10 women ± three years after vitrification. So far, none of the women have returned to utilize their vitrified oocytes. CONCLUSIONS: Oocyte vitrification is a feasible fertility preservation option for women with TS, particularly in those with 46,XX cell lines or sufficient ovarian reserve. Multiple stimulation cycles are recommended to reach an adequate number of vitrified oocytes for pregnancy. It is too early to draw conclusions about the utilization of vitrified oocytes in women with TS.

Anthropometric biomarkers for abnormal prenatal reproductive hormone exposure in women with Mayer-Rokitanksy-Küster-Hauser syndrome, polycystic ovary syndrome, and endometriosis.

OBJECTIVE: To study whether markers of prenatal exposure to reproductive hormones are related to Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, polycystic ovary syndrome (PCOS), and endometriosis. DESIGN: Case-control study. Comparison of sex hormone-related external genital and digital characteristics in cases and controls. SETTING: University hospital. PATIENT(S): We enrolled 172 women in four groups-women with MKRH, women with PCOS, women with endometriosis, and controls (43 in each group). INTERVENTION(S): Measurement of two anthropometric biomarkers: anogenital distance and digit ratio. MAIN OUTCOME MEASURE(S): Anogenital distance was measured from the anus to the anterior clitoral surface (AGDac) and from the anus to the posterior fourchette (AGDaf). For the digit ratio we used a direct, as well as a computer-assisted graphic measurement to measure the length of the second and fourth digit. RESULT(S): After adjustment for body mass index and age, AGDac was the shortest in endometriosis and the longest in PCOS groups, with a mean difference of 10 mm (95% confidence interval 3.1-16.8). AGDaf but not AGDac measures were found to be significantly larger in the MRKH group, with a mean difference compared with controls of 2.6 mm (95% confidence interval 0.1-5.2). The digit ratio was not significantly different between the groups. CONCLUSION(S): In this study we did find limited evidence for androgen exposure during the development of MRKH. This is compatible with the hypothesis that the uterovaginal agenesis may have been the result of temporary prenatal exposure to altered gonadal hormone concentrations. For endometriosis and PCOS we confirm previously observed associations for anogenital distance reflecting possible estrogen-based and androgen-based intrauterine origins, respectively. DUTCH TRIAL REGISTRATION NUMBER: NTR7492.

Effects on asymmetric dimethylarginine of HMR 3339, a novel selective estrogen receptor modulator: a 12-week, randomized, placebo-controlled, double-blind, dose-ranging study in healthy postmenopausal women.

OBJECTIVE: To investigate the short-term effects of three different doses of the selective estrogen receptor modulator HMR 3339 in comparison with placebo and raloxifene on asymmetric dimethylarginine (ADMA), a nitric oxide synthase inhibitor. DESIGN: This study was a multicenter, randomized, placebo-controlled, double-blind, dose-ranging study. Ninety-four healthy postmenopausal women received daily doses of either placebo (n=16), HMR 3339 2.5 mg (n=20), HMR 3339 10 mg (n=19), HMR 3339 50 mg (n=20), or raloxifene 60 mg (n=19) for 12 weeks. Fasting plasma concentrations of ADMA, arginine, and symmetric dimethylarginine (SDMA) were measured at baseline and after 4 and 12 weeks by high-performance liquid chromatography. RESULTS: HMR 3339 induced a dose-dependent reduction of ADMA and SDMA concentrations, with the largest effects (P<0.01 for both) in the HMR 3339 50 mg group compared with baseline and placebo (at 12 weeks: -7.0% [95% CI, -14.2% to 0.2%] for ADMA and -16.2% [95% CI, -22.4% to -10.0%] for SDMA). Twelve weeks of raloxifene 60 mg significantly reduced SDMA (P=0.03) but not ADMA concentrations. Arginine concentrations were not altered by any treatment. CONCLUSIONS: The reduction of the nitric oxide synthase inhibitor ADMA by HMR 3339 may potentially have a beneficial effect on the cardiovascular system in postmenopausal women.

Effect of a combination of isoflavones and Actaea racemosa Linnaeus on climacteric symptoms in healthy symptomatic perimenopausal women: a 12-week randomized, placebo-controlled, double-blind study.

OBJECTIVE: To investigate the effects of a novel dietary supplement containing soy isoflavones and Actaea racemosa Linnaeus (formerly called Cimicifuga racemosa L.) on climacteric symptoms in healthy perimenopausal women. DESIGN: In a multicenter, randomized, placebo-controlled, double-blind study, 124 women experiencing at least five vasomotor symptoms every 24 hours were randomized to receive daily either a phytoestrogen-containing supplement (n = 60) or placebo (n = 64) for 12 weeks. The modified Kupperman Index and Greene Climacteric Scale, a visual analogue scale designed to measure quality of life and the daily number and severity of hot flushes, was used in the screening period and in weeks 6 and 12. Changes in these scores from baseline were calculated. RESULTS: At weeks 6 and 12, all scores in both groups had improved compared with baseline, though the overall difference in scores between the groups was not statistically significant. CONCLUSION: The supplement containing soy isoflavones and A racemosa L. had no statistically significant effect on climacteric symptoms in perimenopausal women experiencing at least five vasomotor symptoms per day.

Effect of hormone replacement therapy on plasma levels of the cardiovascular risk factor asymmetric dimethylarginine: a randomized, placebo-controlled 12-week study in healthy early postmenopausal women.

In a prospective, randomized, placebo-controlled 12-wk study, we investigated the effect of oral hormone replacement therapy on asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), and an independent risk factor for coronary heart disease. The effects on arginine and symmetric dimethylarginine were also investigated. Sixty healthy early postmenopausal women received daily placebo (n = 16) or oral 17beta-estradiol 2 mg, either unopposed (E(2); n = 16) or sequentially combined with dydrogesterone 10 mg (E(2)+D; n = 14) or trimegestone 0.5 mg (E(2)+T; n = 14). ADMA levels reduced in all active treatment groups. Compared with baseline and placebo, the largest reduction in ADMA levels was observed in the E(2)+T group [-18.7% (95% confidence interval [CI], -25.4 to -11.9%) and -21.1% (95% CI, -26.2 to -16.1%), at 4 and 12 wk, respectively]. At 4 and 12 wk in the E(2)+T group, arginine levels were significantly reduced as well [-30.9% (95% CI, -41.1 to -20.7%) and -36.3% (95% CI, -43.1 to -29.5%), respectively], whereas symmetric dimethylarginine levels were significantly lower in the E(2)+D group after 12 wk [-11.6% (95% CI, -19.9 to -3.3%)]. In conclusion, unopposed oral estradiol and estradiol combined with dydrogesterone or trimegestone reduced plasma levels of the NOS inhibitor ADMA. Whether the reduction of the NOS substrate arginine in the E(2)+T group counteracts the potentially beneficial effect of ADMA reduction or reflects increased NO production remains to be investigated.

Effects of high-dose RU-486 treatment on climacteric complaints in hysterectomized postmenopausal women: a 6-week pilot study.

We investigated the effect of the anti-progestogen mifepristone (RU-486) on climacteric complaints. Four hysterectomized postmenopausal women, with at least 35 hot flushes per week, were treated with daily 200mg RU-486 for 6 weeks. RU-486 did not significantly improve climacteric complaints. Although this result does not support further clinical research with this dose of RU-486 for the treatment of climacteric complaints, potential effects of higher, but more interestingly of lower, dosages of RU-486 cannot be excluded.

Serum testosterone levels measured by isotope dilution-liquid chromatography-tandem mass spectrometry in postmenopausal women versus those in women who underwent bilateral oophorectomy.

BACKGROUND: Differentiation between subtle changes in low serum testosterone concentrations, common in women and children, is not possible with current commercially available assays. The objectives of the study were to develop a method based on stable isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) with adequate sensitivity and specificity and to investigate the applicability of this assay in serum samples from pre- and postmenopausal women. METHODS: For 16 women, testosterone levels were measured in blood samples drawn two years before and after physiological menopause, and for eight women in samples drawn before and after bilateral oophorectomy. Testosterone was extracted from serum, derivatized and analysed on an LC-MS/MS. RESULTS: The developed ID-LC-MS/MS method allowed for specific and reproducible measurement of testosterone. Comparison with stable isotope dilution-gas chromatography coupled to mass spectrometry detection by Deming regression analysis gave a slope of 1.025 and an intercept of 0.055 nmol/L (r = 0.9998). A significant decrease was found in testosterone concentrations before and after bilateral oophorectomy (P = 0.02), whereas no significant difference was found before and after natural menopause (P = 0.4). CONCLUSIONS: The ID-LC-MS/MS assay measures serum testosterone with acceptable accuracy and is useful in female samples, supporting the conclusion that the postmenopausal ovary contributes to circulating testosterone. To our knowledge, our analytical method compares favourably to similar published methods in terms of sensitivity. The sensitivity and specificity of this method comply with the reference method for measurement of testosterone in serum samples of women, children and men suffering from hypogonadism and can also be used for men with testosterone in the reference range.

The influence of physiological and surgical menopause on coronary heart disease risk markers.

OBJECTIVE: To investigate the influence of physiological and surgical menopause on serum concentrations of coronary heart disease (CHD) risk markers and sex hormones. DESIGN: Physiological menopausal transition was investigated in two studies. In a longitudinal study, 16 women were followed from 2 years before until 2 years after physiological menopause. In a case-control study, 27 early postmenopausal women were compared with 27 age-matched late premenopausal women. Surgical menopause was investigated in 11 women undergoing a prophylactic bilateral salpingo-oophorectomy. The following parameters were measured: serum concentrations of estradiol, follicle-stimulating hormone, inhibin A, inhibin B, asymmetric dimethylarginine, lipids, leptin, homocysteine, C-reactive protein, and coenzyme Q10, as well as weight and body mass index. RESULTS: After physiological and surgical menopause, serum estradiol and inhibin A and B decreased, whereas follicle-stimulating hormone increased (all P values < 0.01). Serum asymmetric dimethylarginine, total and low-density lipoprotein cholesterol, and leptin concentrations were significantly higher in postmenopausal women compared with premenopausal women (all P values < 0.05). Serum homocysteine concentrations increased significantly during the physiological menopausal transition. Total and low-density lipoprotein cholesterol increased after surgical menopause (both P values = 0.01). None of the other parameters studied were influenced significantly by the menopausal transition. No difference in change in the various CHD risk markers investigated was observed between physiological and surgical menopause. CONCLUSIONS: The CHD risk profile was affected unfavorably by both physiological and surgical menopause. Changes in most CHD risk markers were small, despite the substantial changes in hormonal parameters.

Effects of intranasal versus oral hormone therapy on asymmetric dimethylarginine in healthy postmenopausal women: a randomized study.

OBJECTIVE: Oral estrogens reduce asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and an independent risk factor for cardiovascular disease. This study was conducted to compare the effect on ADMA between intranasal and oral 17beta-estradiol (E2) combined with norethisterone (acetate) (NET(A)) administration in postmenopausal women. METHODS: In a two-center, randomized, double-blind, comparative study 90 healthy postmenopausal women (age 56.6+/-4.7 years) received daily continuous combined intranasal E2/NET 175 microg/275 microg (n=47) or oral E2/NETA 1 mg/0.5 mg (n=43) for one year. At baseline, week 12 and 52, plasma concentrations of ADMA, arginine and symmetric dimethylarginine (SDMA) were measured by high-performance liquid chromatography. RESULTS: Oral E2/NETA reduced ADMA concentrations (-7.4%; 95% confidence interval (CI) -10.4 to -4.4%), while intranasal E2/NET had no effect (-0.8%; 95% CI -3.7 to 2.1%) after 52 weeks. In both groups, arginine was transiently decreased compared to baseline at week 12 (intranasal: -6.1%; 95% CI -9.1 to -3.0%; oral: -6.5%; 95% CI -10.9 to -2.1%). Only oral E2/NETA reduced SDMA concentrations. CONCLUSIONS: Oral administration of E2/NETA reduced ADMA and SDMA concentrations, whereas intranasal administration did not. Both treatments transiently reduced arginine. The decrease in ADMA by oral estrogens could be a key phenomenon in the modulation of nitric oxide synthesis by postmenopausal hormone therapy.

Effects of a supplement containing isoflavones and Actaea racemosa L. on asymmetric dimethylarginine, lipids, and C-reactive protein in menopausal women.

OBJECTIVE: To investigate the effects of a supplement containing soy isoflavones and Actaea racemosa L. on several coronary heart disease (CHD) risk markers in menopausal women. DESIGN: Randomized, placebo-controlled, double-blind study. SETTING: Nine hospitals in The Netherlands. PATIENT(S): One hundred twenty-four menopausal women. INTERVENTION(S): Daily placebo (n = 64) or supplement containing soy isoflavones and Actaea racemosa L. (n = 60) for 12 weeks. MAIN OUTCOME MEASURE(S): Fasting blood concentrations of asymmetric dimethylarginine (ADMA), lipids, and C-reactive protein (CRP) at baseline and week 12. RESULT(S): In the supplement group, total cholesterol and low-density lipoprotein cholesterol showed a small absolute reduction at week 12 (-0.2, 95% confidence interval [CI] -0.3 to -0.0; and -0.2, 95% CI -0.3 to -0.0; respectively). Concentrations of ADMA, triglycerides, lipoprotein(a), and CRP did not change significantly. Analysis of covariance over the 12-week study period revealed no significant between-group differences for all parameters. No significant correlations were found between the concentrations of isoflavones and the CHD risk markers investigated. CONCLUSION(S): Twelve-week administration of a supplement containing soy isoflavones and Actaea racemosa L. had little or no influence on the CHD risk markers studied. This supplement probably has neither protective nor adverse effects on the cardiovascular system; however, large long-term studies are needed to test this.