Impact of bariatric surgery on ovarian reserve markers and its correlation with nutritional parameters and adipokines.

Introduction: A reduction in anti-müllerian hormone (AMH) levels at short-term after bariatric surgery (BS) has been previously described. However, an assessment of ovarian reserve at longer-follow up, and a comprehensive evaluation of the potentially implicated factors has not been reported. Design: Prospective cohort study. Materials and methods: Twenty women aged 18-40 years with BMI 43.95 kg/m2 undergoing BS were studied at baseline (BS0), and at 1 month (BS1), 4 months (BS2), 12 months (BS3), and 24-36 months (BS4) after the surgery. Anthropometrics, reproductive hormones (AMH, FSH, LH, estradiol, testosterone, SHBG, androstenedione), metabolic parameters (adiponectin, leptin, ghrelin, insulin), and nutritional blood parameters (markers of nutritional status, vitamins, and minerals) were obtained at each study time point. Antral follicular count (AFC) was assessed by ultrasonography at BS0, BS3, and BS4. Mixed models were used for analysis of longitudinal data. Results: The mean AMH level was 3.88 ng/mL at BS0, decreased at BS3 (mean= 2.59 ng/mL; p=0.009), and remained stable between BS3 and BS4 (mean= 2.96 ng/mL; p=0.409). We also observed a non-significant decrease in AFC at BS3 (mean=26.14 at BS0, mean 16.81 at BS3; p=0.088) that remained stable at BS4 (mean= 17.86; p=0.731). Mixed models analysis showed: (a) a decrease in 10 kg of body weight was associated with an average decrease of 0.357 ng/mL in AMH (p=0.014); (b) a decrease in 1 BMI point was associated with an average decrease of 0.109 ng/mL in AMH (p=0.005); (c) an increase in 1 µg/mL of adiponectin was associated with an average decrease of 0.091 ng/ml in AMH (p=0.041) Significant positive correlations were found between the AMH levels after BS and plasma concentrations of testosterone, free androgen index, insulin and HOMA index. No significant correlations were detected between AMH levels and nutritional parameters. Conclusions: Our results were in line with previous observations, showing that AMH levels decreased significantly at 12 months after bariatric surgery, in parallel with a non-significant reduction in AFC. Both ovarian reserve markers showed a later stabilization up to the end of the study. Of note, postoperative AMH levels were positively correlated with key androgen and insulin resistance-related parameters.

Current status of fertility preservation in a Spanish tertiary public hospital: multidisciplinary approach and experience in over 1500 patients.

PURPOSE: Currently, 15% of gynaecological and 9% of haematological malignancies are diagnosed before the age of 40. The increased survival rates of cancer patients who are candidates for gonadotoxic treatments, the delay in childbearing to older ages, and the optimization of in vitro fertilisation techniques have all contributed to an increased interest in fertility preservation (FP) treatments. This study reviews the experience of the Fertility Preservation Programme (FPP) of a tertiary public hospital with a multidisciplinary approach. METHODS: This retrospective study included all the available (FP) treatments, performed in patients of childbearing age between 2006 and 2022. RESULTS: 1556 patients were referred to the FPP: 332 oocyte vitrification cycles, 115 ovarian cortex cryopreservation with 11 orthotopic autotransplantations, 175 gonadotropin-releasing hormone (GnRH) agonist treatments, 109 fertility-sparing treatments for gynaecological cancer, and 576 sperm cryopreservation were performed. Malignancy was the main indication for FP (the main indications being breast cancer in women and haematological malignancies in men), although non-oncological pathologies, such as endometriosis and autoimmune diseases, have increased in recent years. Currently, the most widely used FP technique is oocyte vitrification, the increase of which has been associated with a decrease in the use of cortex CP and GnRH agonists. CONCLUSIONS: The increase in FP treatment reflects the implementation of reproductive counselling in oncology programmes. A multidisciplinary approach in a tertiary public hospital allows individualised FP treatment for each patient. In recent years, there has been a change in trend with the introduction of new indications for FP and a change in techniques due to their optimisation.

Comparison between slow freezing and vitrification of ovarian tissue cryopreservation in assigned female at birth transgender people receiving testosterone therapy: data on histological and viability parameters.

PURPOSE: The use of fertility preservation (FP) techniques has significantly increased in recent years in the assigned female at birth (AFAB) transgender population. Oocyte cryopreservation is the established method for FP, but ovarian tissue cryopreservation may be considered an alternative option, especially during gender-affirming surgery (GAS). The slow freezing (SF) cryopreservation technique is the standard method for human ovarian tissue, but recently, several studies have shown good results with the vitrification (VT) technique. The objective of this study was to compare the effectiveness of VT and SF techniques in ovarian tissue from AFAB transgender people. METHODS: This was a prospective study including 18 AFAB transgender people after GAS. Ovarian tissue pieces from each ovary were cryopreserved by SF and VT and compared with fresh tissue. Study by light microscopy (LM) assessed follicular morphology and density. The percentage of surviving and degenerated follicles was studied with the tissue viability test. Oocytes, granulosa cells and stroma were analysed separately by transmission electron microscopy. RESULTS: The VT technique preserves follicle and stromal tissue as well as the SF method, but with some differences. Evaluation by LM showed better follicle preservation with VT, but the ultrastructural study showed the presence of minor damage with both techniques compared to fresh tissue. CONCLUSION: Both cryopreservation techniques are accurate for maintaining the follicular population and stromal tissue. Further studies are needed to determine the impact of VT on ovarian tissue and the subsequent follicular activation mechanisms in AFAB ovarian tissue.

Endocrinological and ovarian histological investigations in assigned female at birth transgender people undergoing testosterone therapy.

RESEARCH QUESTION: What are the hormonal and ovarian histological effects of a gender affirming hormonal therapy in assigned female at birth (AFAB) transgender people? DESIGN: Prospective observational study of 70 AFAB transgender people taking testosterone therapy before gender-affirming surgery (hystero-oophorectomy). A gynaecological ultrasonographic scan was undertaken and serum hormone concentrations measured, including anti-Müllerian hormone (AMH) and androgenic profile. Histological ovarian evaluation was assessed in both ovaries, including the developmental stages of the follicles. RESULTS: The mean age of the population was 27.7+/-5.14 years. The main biochemical parameters were total testosterone levels 781.5 ± 325.9 ng/dl; AMH levels 3.2 ± 1.4 ng/ml; FSH and LH levels 4.9 ± 2.5 IU/l and 3.9 ± 2.9 IU/l, respectively; and oestradiol values 47.6 ± 13.7 pg/ml. Fifty-five AFAB underwent gynaecological ultrasound before surgery and antral follicles were found in 43 out of 47 ultrasounds (91.5%) (without the presence of a dominant follicle or corpus luteum). Histological follicles were mostly in the primordial stage (88.0) and 3.3% were atretic. The thickness of the tunica albuginea was widely heterogeneous (range 0.15-1.45 mm) and luteinization of the stromal cells was observed in 68.6% of the samples. A negative correlation between testosterone levels and total antral follicles was found (Rs= -0.306, P = 0.029). CONCLUSIONS: AFAB transgender people taking testosterone therapy show cortical follicle distribution in the range previously reported in fertile cisgender women of reproductive age. The follicular population may not be altered as a result of the gender-affirming hormonal therapy, although some cortical and stromal changes have been observed.

Drug-free in-vitro activation of follicles and fresh tissue autotransplantation as a therapeutic option in patients with primary ovarian insufficiency.

RESEARCH QUESTION: Could in-vitro action of follicles and fresh tissue autotransplantation without tissue culture (drug-free IVA) be useful in patients with primary ovarian insufficiency (POI)? DESIGN: Prospective observational cohort study in a tertiary university hospital. Drug-Free IVA was carried out in 14 women with POI with a median age of 33 years (29-36 years), median length of amenorrhoea of 1.5 years (1-11 years), median FSH levels 69.2 mIU/ml (36.9-82.8 mIU/ml) and anti-Müllerian hormone of 0.02 ng/ml (0.01-0.1 ng/ml). The surgical procedure included laparoscopic removal of ovarian cortex, fragmentation of tissue and autografting. Human menopausal gonadotrophin (HMG) was started immediately after surgery. RESULTS: Follicle development was detected in seven out of the 14 patients, and five women achieved successful oocyte retrieval. In six women, HCG was administered in 10 cycles. Six embryo transfers were carried out in five women resulting in four pregnancies; a clinical pregnancy rate of four in seven oocyte retrievals and four in six embryo transfers. CONCLUSIONS: Drug-free IVA could be a useful therapeutic option for patients with POI, leading to successful IVF outcomes.

Age, independent from ovarian reserve status, is the main prognostic factor in natural cycle in vitro fertilization.

OBJECTIVE: To analyze natural cycle IVF (NC-IVF) results according to patient age, ovarian reserve status following the Bologna criteria, cause of infertility, and modification of the cycle with the use of GnRH antagonist. DESIGN: Retrospective cohort study. SETTING: Tertiary-care university hospital. PATIENT(S): Nine hundred forty-seven natural cycles carried out in 320 patients. INTERVENTION(S): Analysis of 947 NC-IVF outcomes performed in one single center between January 2010 and December 2014. MAIN OUTCOME MEASURE(S): Pregnancy rates per cycle started, per ET, and per patient, as well as ongoing pregnancy rate at a minimum of 12 weeks of gestation. RESULT(S): Among the three age groups analyzed (≤35 years, 36-39 years, and ≥40 years), pregnancy rates per cycle were significantly lower in the older group of patients (11.4% vs. 11.6% vs. 5.9%). In addition, miscarriage rate (7.7% vs. 34.4% vs. 50%) and ongoing pregnancy rate (10.6% vs. 7.6%vs. 3.0%) were negatively affected by patient age. However, no differences were observed according to patient ovarian reserve status, cause of infertility, or modification of the cycle with GnRH antagonist. The multivariate logistic regression confirmed that patient age was the only variable that could predict pregnancy in NC-IVF cycles (odds ratio, 0.93; 95% confidence interval, 0.88-0.98). CONCLUSION(S): NC-IVF is a feasible and "patient-friendly" option to be offered to young patients, independent of their ovarian reserve status.