BCORL1, POF1B, and USP9X copy number variation in women with idiopathic diminished ovarian reserve.

PURPOSE: To analyze the copy number variation (CNV) in the X-linked genes BCORL1, POF1B, and USP9X in idiopathic diminished ovarian reserve (DOR). METHODS: This case-control study included 47 women, 26 with DOR and 21 in the control group. Age, weight, height, BMI, and FSH level were evaluated, as well as antral follicle count (AFC), oocyte retrieval after controlled ovarian stimulation, and metaphase II (MII) oocytes. The CNVs of BCORL1, USP9X, and POF1B genes were measured by quantitative real time PCR (qPCR) using two reference genes, the HPRT1 (X-linked) and MFN2 (autosomal). Protein-protein interaction network and functional enrichment analysis were performed using the STRING database. RESULTS: The mean age was 36.52 ± 4.75 in DOR women and 35.38 ± 4.14 in control. Anthropometric measures did not differ between the DOR and control groups. DOR women presented higher FSH (p = 0.0025) and lower AFC (p < .0001), oocyte retrieval after COS (p = 0.0004), and MII oocytes (p < .0001) when compared to the control group. BCORL1 and POF1B did not differ in copy number between DOR and control. However, DOR women had more copies of USP9X than the control group (p = 0.028). CONCLUSION: The increase in the number of copies of the USP9X gene may lead to overexpression in idiopathic DOR and contribute to altered folliculogenesis and oocyte retrieval.

Altered ovarian reserve in Ewe lambs exposed to a glyphosate-based herbicide.

Glyphosate-based herbicides (GBHs) are considered endocrine disruptors that affect the female reproductive tract of rats and ewe lambs. The present study aimed to investigate the impact of neonatal exposure to a low dose of a GBH on the ovarian follicular reserve of ewe lambs and the response to a gonadotropic stimulus with porcine FSH (pFSH). To this end, ewe lambs were orally exposed to an environmentally relevant GBH dose (1 mg/kg/day) or vehicle (Control) from postnatal day (PND) 1 to PND14, and then some received pFSH (50 mg/day) between PND41 and 43. The ovaries were dissected, and follicular types and gene expression were assessed via RT-PCR. The treatments did not affect the body weight of animals, but pFSH increased ovarian weight, not observed in GBH-exposed lambs. GBH-exposed lambs showed decreased Estrogen receptor-alpha (56%), Progesterone receptor (75%), Activin receptor II (ACVRII) (85%), and Bone morphogenetic protein 15 (BMP15) (88%) mRNA levels. Control lambs treated with pFSH exhibited downregulation of Follistatin (81%), ACVRII (77%), BMP15 (93%), and FSH receptor (FSHr) (72%). GBH-exposed lambs treated with pFSH displayed reduced ACVRII (68%), BMP15 (81%), and FSHr (50%). GBH-exposed lambs also exhibited decreased Anti-Müllerian hormone expression in primordial and antral follicles (27%) and (54%) respectively) and reduced Bone morphogenetic protein 4 (31%) expression in primordial follicles. Results suggest that GBH disrupts key follicular development molecules and interferes with pFSH action in ovarian receptors, decreasing the ovarian reserve. Future studies should explore whether this decreased ovarian reserve impairs adult ovarian function and its response to superovulation stimuli.

Low and High-Normal FMR1 Triplet Cytosine, Guanine Guanine Repeats Affect Ovarian Reserve and Fertility in Women Who Underwent In Vitro Fertilization Treatment? Results from a Cross-Sectional Study.

Dynamic mutations in the 5' untranslated region of FMR1 are associated with infertility. Premutation alleles interfere with prenatal development and increase infertility risks. The number of CGG repeats that causes the highest decrease in ovarian reserves remains unclear. We evaluated the effect of FMR1 CGG repeat lengths on ovarian reserves and in vitro fertilization (IVF) treatment outcomes in 272 women with alleles within the normal range. FMR1 CGG repeat length was investigated via PCR and capillary electrophoresis. Alleles were classified as low-normal, normal, and high-normal. Serum levels of follicle-stimulating hormone and anti-Mullerian hormone (AMH) in the follicular phase of the menstrual cycle were measured, and antral follicles (AFC) were counted. IVF outcomes were collected from medical records. Regarding FMR1 CGG repeat length alleles, 63.2% of women presented at least one low-normal allele. Those carrying low-normal alleles had significantly lower AMH levels than women carrying normal or high-normal alleles. Low-normal/low-normal genotype was the most frequent, followed by low-normal/normal and normal/normal. A comparison of ovarian reserve markers and reproductive outcomes of the three most frequent genotypes revealed that AFC in the low-normal/normal genotype was significantly lower than the low-normal/low-normal genotype. The low number of FMR1 CGG repeats affected AMH levels and AFC but not IVF outcomes per cycle of treatment.

Evaluation of ovarian reserve in women with thyroid autoimmunity.

OBJECTIVE: To compare the ovarian reserve of women of reproductive age with and without thyroid autoimmunity (TAI). METHODS: We performed a retrospective analysis of medical records from an assisted reproduction clinic from February 2017 to December 2021. Women aged between18 and 47 years with data on antithyroperoxidase and antithyroglobulin (anti-Tg) antibodies and assessment of ovarian reserve by anti-müllerian hormone (AMH) and antral follicle count (AFC) were included. Among the 188 participants included, 63 were diagnosed with TAI, and 125 had both antibodies negative. AMH and AFC were compared between groups. Subanalysis based on age, types of antibodies, and thyroid function markers were performed. In addition, bivariate analysis and regression models were used. RESULTS: Overall, there was no difference in the median levels of AMH or AFC between the two groups. However, in the subgroup analysis by age, we observed a trend towards lower median levels of AMH in women over 39 years with TAI (0.9 ng/mL vs. 1.5 ng/mL, p=0.08). In a subanalysis according to antibodies, we found a significantly lower median AFC in the group with anti-Tg than in the group without this antibody (8.0 follicles vs. 11.5 follicles, p=0.036). We also found a significantly higher prevalence of anti-Tg in patients with low ovarian reserve compared to those with normal reserve (60.7% vs. 39.3%, p=0.038). CONCLUSIONS: The ovarian reserve of women with TAI appears to be insidiously compromised over the years, with a decreased ovarian reserve in women with anti-Tg.

Intraovarian platelet-rich plasma injection in poor responders.

OBJECTIVE: To evaluate if it possible to improve ovarian reserve parameters and oocyte retrieval in poor responders who undergo intraovarian injection of platelet-rich plasma (PRP). METHODS: Prospective cohort study. We included 148 poor responders who underwent PRP injection between October 2021 and December 2022 in our institution, comparing pre and post PRP ovarian function. In addition, the IVF outcomes of a subgroup of patients was studied after the intervention in contrast with the previous treatment. RESULTS: An improvement in ovarian reserve was observed in relation to previous values: FSH (13.57 vs. 11.32, p=0.11), AMH (0.39 vs. 0.48, p=0.06), antral follicle count (3.98 vs. 5.75, p<0.001); as well as a higher number of oocytes retrieved (2.63 vs. 3.65, p=0.01) and produced embryos (1.64 vs. 2.22, p=0.03); without a great impact on pregnancy rates. CONCLUSIONS: Although experimental, intraovarian PRP could restore ovarian function and be postulated as an alternative to oocyte donation in patients with low ovarian reserve who do not accept this treatment. There is a lack of randomized controlled trials to support these findings.

Dynamics of serum exosome microRNA profile altered by chemically induced estropause and rescued by estrogen therapy in female mice.

The decline in the ovarian reserve leads to menopause and reduced serum estrogens. MicroRNAs are small non-coding RNAs, which can regulate gene expression and be secreted by cells and trafficked in serum via exosomes. Serum miRNAs regulate tissue function and disease development. Therefore, the aim of this study was to identify miRNA profiles in serum exosomes of mice induced to estropause and treated with 17ß-estradiol (E2). Female mice were divided into three groups including control (CTL), injected with 4-Vinylcyclohexene diepoxide (VCD), and injected with VCD plus E2 (VCD + E2). Estropause was confirmed by acyclicity and a significant reduction in the number of ovarian follicles (p < 0.05). Body mass gain during estropause was higher in VCD and VCD + E2 compared to CTL females (p = 0.02). Sequencing of miRNAs was performed from exosomes extracted from serum, and 402 miRNAs were detected. Eight miRNAs were differentially regulated between CTL and VCD groups, seven miRNAs regulated between CTL and VCD + E2 groups, and ten miRNAs regulated between VCD and VCD + E2 groups. Only miR-200a-3p and miR-200b-3p were up-regulated in both serum exosomes and ovarian tissue in both VCD groups, suggesting that these exosomal miRNAs could be associated with ovarian activity. In the hepatic tissue, only miR-370-3p (p = 0.02) was up-regulated in the VCD + E2 group, as observed in serum. Our results suggest that VCD-induced estropause and E2 replacement have an impact on the profile of serum exosomal miRNAs. The miR-200 family was increased in serum exosomes and ovarian tissue and may be a candidate biomarker of ovarian function.

Senolytic treatment fails to improve ovarian reserve or fertility in female mice.

Senescent cell number increases with age in different tissues, leading to greater senescent cell load, proinflammatory stress, and tissue dysfunction. In the current study, we tested the efficacy of senolytic drugs to reduce ovarian senescence and improve fertility in reproductive age female mice. In the first experiment, 1-month-old C57BL/6 female mice were treated every other week with D + Q (n = 24) or placebo (n = 24). At 3 and 6 months of age, female mice were mated with untreated males to evaluate pregnancy rate and litter size. In the second experiment, 6-month-old C57BL/6 female mice were treated monthly with D + Q (n = 30), fisetin (n = 30), or placebo (n = 30). Females were treated once a month until 11 months of age, then they were mated with untreated males for 30 days to evaluate pregnancy rate and litter size. In the first experiment, D + Q treatment did not affect pregnancy rate (P = 0.68), litter size (P = 0.58), or ovarian reserve (P > 0.05). Lipofuscin staining was lower in females treated with D + Q (P = 0.04), but expression of senescence genes in ovaries was similar. In the second experiment, D + Q or fisetin treatment also did not affect pregnancy rate (P = 0.37), litter size (P = 0.20), or ovarian reserve (P > 0.05). Lipofuscin staining (P = 0.008) and macrophage infiltration (P = 0.002) was lower in fisetin treated females. Overall, treatment with D + Q or fisetin did not affect ovarian reserve or fertility but did decrease some senescence markers in the ovary.

Serum anti-Müllerian hormone is lower in patients with multiple radioiodine dose for treatment of pediatric thyroid cancer.

Introduction: Treatment of patients with pediatric differentiated thyroid cancer (DTC) often involves radioiodine (RAI), which is associated with increased risks of short- and long-term adverse outcomes. The impact of RAI treatment on the female reproductive system remains uncertain. Anti-Müllerian hormone (AMH) is a marker of ovarian reserve and is related to fertility. Objective: The aim was to analyze the association between RAI and serum AMH level in women treated with RAI. Methods: We evaluated women with pediatric DTC treated with RAI at the age of ≤19 years. Serum AMH was measured. Results: The study included 47 patients with a mean age of 25.1 years (12.4-50.8) at AMH measurement and follow-up of 11.8 ± 8.4 years. The mean RAI administered was 235 mCi (30-1150). Sixteen (34%) received multiple RAI doses (471 ± 215 mCi). Mean AMH level was 2.49 ng/mL (0.01-7.81); the level was 1.57 ng/mL (0.01-7.81) after multiple RAI doses and 2.99 ng/mL (0.01-6.63) after a single RAI dose (P = 0.01). Patients who received a cumulative RAI lower than 200 mCi had higher AMH levels (2.23 ng/mL, 0.39-7.81) than those who received more (1.0 ng/mL, 0.01-6.63; P = 0.02). In patients with similar cumulative RAI activities, administration of multiple RAI doses was significantly and independently associated with AMH level lower than the reference range for age (HR: 5.9, 1.55-52.2, P = 0.014) after age adjustments. Conclusion: Levels of AMH were lower after multiple RAI doses, especially after a cumulative RAI dose above 200 mCi. More studies are needed to clarify the impact of RAI on fertility considering its cumulative activity and treatment strategy.

Frequency of diminished ovarian reserve in women with multiple sclerosis in Chile: An exploratory study.

INTRODUCTION: Multiple Sclerosis (MS) is a chronic disease affecting around 2.8 million people worldwide. Two-thirds are women, and the mean age at diagnosis is about 30 years old. Social trends are moving towards older age at first pregnancy, both in women with and without MS. OBJECTIVES: To determine the frequency of diminished ovarian reserve (DOR) through anti-Mullerian Hormone (AMH) measurement in women with MS at fertile age and Healthy Females (HF) in Chile. METHODS: Case-control, multicentric, cross-sectional study including relapsing-remitting people with MS (pwMS) between 18 and 40 years and sex and age-matched HF. We obtained a blood sample to determine AMH levels. We defined DOR as AMH <1.5 ng/mL and very-low AMH levels as <0.5 ng/mL. Also, we performed questions regarding reproductive decision-making. RESULTS: We included 79 sex and age-matched HF and 92 pwMS, median age 32(19-40) years, median disease duration 6 (1-17)years, median EDSS 1.0 (0-6), 95% were receiving disease-modifying therapy (DMT), 70% high-efficacy DMT and 37% with a treatment that contraindicates pregnancy. DOR was observed in 24% (n = 22) of the pwMS, compared to 14% (n = 11) of the HF (p = 0.09), while very-low AMH levels were observed in 7.6% (n = 7) of pwMS and none of the HF (p = 0.0166). We observed an inverse correlation between age and AMH levels. Age was the only significant risk factor for low AMH levels in pwMS (OR 1.14 95%CI(1.00-1-31), p = 0.04), including smoking, body mass index (BMI), hormonal contraception, autoimmune comorbidity, high/low-moderate efficacy DMT, and active disease as covariables. We did not find statistically significant differences in age at diagnosis, BMI, disease duration, EDSS, autoimmune comorbidity, use of hormonal contraception, or percentage of active disease between MS women with normal vs DOR. Over 70% of pwMS desired to become pregnant in the future, while 60% considered that the diagnosis of MS was a limitation for pregnancy planning. CONCLUSIONS: No differences in DOR, measured by levels of AMH, were observed between pwMS MS and HF in Chile. As expected, AMH levels were correlated only with ageing. This information may be evaluated early during the disease course to help patients and neurologists with fertility counselling and family planning considerations regarding DMT use.

O hormônio antimulleriano e a reserva ovariana: uma revisão integrativa da literatura / The anti-mullerian hormone and the ovarian reserve: an integrative literature review

O hormônio antimulleriano é secretado pelas células da granulosa dos folículos que estão em desenvolvimento no ovário. Por meio da sua dosagem, é possível avaliar a reserva ovariana. A mulher tem seu número máximo de oócitos no perío- do fetal, mas, conforme o tempo passa, existe uma queda do número de células germinativas. Desse modo, para mulheres que têm o desejo de engravidar, a dosa- gem de hormônios e a avaliação da reserva ovariana podem ajudar no processo. O objetivo do estudo foi encontrar evidências na literatura que comprovem que o hormônio antimulleriano é o melhor marcador da reserva ovariana. Para isso, foi realizada uma revisão integrativa, classificada como qualitativa; a busca de da- dos foi realizada no PubMed, utilizando a seguinte palavra-chave: "hormônio anti- mulleriano (HAM)". Foram encontrados oito artigos que abordavam diretamente o tema, e há evidências que corroboram a hipótese de que o hormônio antimulleria- no é um bom marcador da reserva ovariana, sendo necessários mais estudos para determinar a sua superioridade.

The anti-mullerian hormone is secreted by the granulosa cells of follicles that are developing in the ovary. Though its dosage is possible to evaluate the ovarian re- serve. Women have their maximum number of oocytes in the fetal period, but there is a decrease in the number of germinative cells as time goes by. Thus, women that desire to get pregnant can have hormones dosed and the ovarian reserve evalua- ted to help them with this process. The objective of this study was to find evidence in the literature that proves that the anti-mullerian hormone is the best marker of ovarian reserve. For this purpose, an integrative review was conducted, using the key word: "anti-mullerian hormone (AMH)". Eight articles were found on the subject and there is evidence that proves the hypothesis of the anti-mullerian hormone as a good marker, however more studies are needed to determine its superiority.

Involvement of SYCP2L and TDRD3 gene variants on ovarian reserve and reproductive outcomes: a cross-sectional study.

OBJECTIVE: Single nucleotide variants have been implicated in the response to fertility treatment and a pharmacogenomic approach may help to customize therapy based on patient genome. We aimed to evaluate the effect, individual and combined, of SYCP2L (rs2153157:G>A) and TDRD3 (rs4886238:G>A) variants on ovarian reserve, response to controlled ovarian stimulation (COS) and reproductive outcomes of women undergoing in vitro fertilization (IVF) treatment. METHODS: This cross-sectional study included 149 normoovulatory women undergoing IVF. Genotyping was performed using the TaqMan real-time polymerase chain reaction method. Clinical parameters and reproductive outcomes were compared according to the genotypes of the variants studied. RESULTS: Considering ovarian reserve, there were no significant differences among SYCP2L or TDRD3 genotypes in terms of FSH levels or AFC; however, AMH levels were significantly different in carriers of both variants. Regarding the SYCP2L rs2153157:G>A variant, lower AMH levels were observed in women carrying an AA genotype compared to women carrying a heterozygous genotype (p=0.01). Considering the TDRD3 rs4886238:G>A variant, women carrying an AA genotype presented higher AMH levels than carriers of GG and GA genotypes (p=0.025). Nevertheless, no difference was found regarding response to COS or reproductive outcomes. Considering the combined effect of the variants, women carrying the heterozygous genotype of both variants presented statistically increased AMH levels compared to SYCP2L rs2153157 AA genotype carriers and TDRD3 rs4886238 GG genotype carriers (p=0.042). CONCLUSIONS: Individually and combined, the SYCP2L rs2153157 and TDRD3 rs4886238 variants have an effect on AMH level.

Iron intake in relation to ovarian reserve among women seeking infertility treatment.

STUDY QUESTION: Is there an association between iron intake and ovarian reserve among women seeking fertility care? SUMMARY ANSWER: Supplemental iron intake above 45 mg/day is associated with lower ovarian reserve among women seeking fertility care. WHAT IS KNOWN ALREADY: Although the literature regarding iron intake in relation to ovarian reserve is scant and inconsistent, some evidence suggests that iron may have gonadotoxic effects. STUDY DESIGN, SIZE, DURATION: This observational study included 582 female participants attending the Massachusetts General Hospital Fertility Center (2007-2019) enrolled in the Environment and Reproductive Health (EARTH) Study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Iron intake was estimated using a validated food frequency questionnaire. Markers of ovarian reserve included antral follicle count (AFC) (assessed via transvaginal ultrasound) and Day 3 FSH, both obtained during the course of an infertility evaluation. MAIN RESULTS AND THE ROLE OF CHANCE: Participants had a median age of 35 years and median total iron intake of 29 mg/day. Total iron intake was inversely related to AFC and this association was driven by intake of supplemental iron. Compared to women with a supplemental iron intake of ≤20 mg/day, women consuming 45-64 mg/day of supplemental iron had a 17% (-35%, 0.3%) lower AFC and women consuming ≥65 mg/day of supplemental iron had a 32% (-54%, -11%) lower AFC after adjusting for potential confounders (P, linear trend = 0.003). Similarly, in a multivariable-adjusted analysis, Day 3 FSH levels were 0.9 (0.5, 1.3) IU/ml higher among women with a supplemental iron intake of ≥65 mg/day when compared to women with a supplemental iron intake of ≤20 mg/day (P, linear trend = 0.02). LIMITATIONS, REASONS FOR CAUTION: Iron intake was estimated using a method that relies on self-report and we had no biomarkers of iron status in our participants; only 36 women consumed ≥45 mg/day of supplemental iron. WIDER IMPLICATIONS OF THE FINDINGS: Since all study participants were seeking fertility treatment, our findings may not apply to women in the general population. Although our findings are consistent with studies of women with iron overload, given the paucity of literature on this topic, it is essential that this question is revisited in studies designed to better understand the dose-response relation of this association across the entire distribution of ovarian reserve and the risk-benefit balance of pre-conceptional iron supplementation given its many positive effects on pregnancy outcomes. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by Grants R01ES022955, R01ES033651, R01ES009718, P30ES000002, and P30DK046200 from the National Institutes of Health. N.J.-C. was supported by a Fulbright Scholarship. N.J.-C., M.M., L.M.-A., E.O.-P., S.W., I.S., and J.E.C. declare no conflict of interest related to the work in the manuscript. R.H. has received grants from the National Institute of Environmental Health Sciences. TRIAL REGISTRATION NUMBER: N/A.

Ovarian reserve in adolescent girls with autoimmune thyroiditis.

Objective: To assess serum anti-Müllerian hormone (AMH) levels as an ovarian reserve marker in adolescent girls with autoimmune thyroiditis (AIT) and explore the relationship of this marker with autoimmunity and thyroid function biomarkers. Subjects and methods: This study included 96 adolescent girls with newly diagnosed AIT and 96 healthy, age- and sex-matched controls. All participants were evaluated with detailed history taking and physical examination, thyroid ultrasound, and measurement of levels of thyroid-stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), antithyroid peroxidase antibodies (TPOAb), antithyroglobulin antibody (TGAb), estradiol, total testosterone, and anti-Müllerian hormone (AMH) levels. The LH/FSH ratio was also calculated. Among 96 patients evaluated, 78 were overtly hypothyroid and 18 were euthyroid. AMH levels were significantly lower in participants with overt hypothyroidism and euthyroidism compared with controls. Results: Serum levels of AMH correlated negatively with age, body mass index (BMI) standard deviation score (SDS), and TPOAb, TGAb, and TSH levels but positively with FT4 levels. In multivariate analysis, AMH levels correlated significantly with age (odds ratio [OR] = 1.65, 95% confidence interval [CI] 1.18-2.32, p = 0.05), BMI SDS (OR = 2.3, 95% CI, 2.23-3.50, p = 0.01), TSH (OR = 2.43, 95% CI 1.5-2.8, p = 0.01), and TPOAb (OR = 4.1, 95% CI 3.26-8.75, p = 0.001). Conclusion: Ovarian reserve of adolescent girls with AIT, as measured by serum AMH levels, is affected by thyroid autoimmunity and hypothyroidism, indicating a possible need for ovarian reserve monitoring in these patients.

The size, number and bilaterality of endometriomas do not affect spontaneous conception chance following surgical removal.

OBJECTIVE: Endometrioma surgery is associated with a reduction in ovarian reserve. However, removal of an endometrioma may increase the likelihood of a spontaneous conception. The objective of this study was to assess the pre-operative and operative variables affecting spontaneous conception following endometrioma surgery. METHODS: Data from 211 women ≤40 years of age who underwent an endometrioma surgery at a university-based infertility clinic between January 2005 and June 2020 were reviewed retrospectively. The main outcome measure was spontaneous clinical pregnancy. We had 84 women with and 127 women without a successful spontaneous conception making up the case and control groups. RESULTS: The median ages of the cases and controls were 27 and 32 years, respectively (p<0.001). The rate of recurrence was significantly lower in the spontaneous conception group when compared to controls (29.8% vs. 52.8%, respectively; p=0.001). Our results showed no differences in the number, size, or side of the endometriomas in both groups. Multivariate logistic regression analysis showed significant independent effects of age (B: -.166, OR {odds ratio}: 0.847, 95% CI {confidence interval}: 0.791-0.907, p<0.001), recurrence (B: -1.030, OR: 0.357, 95% CI: 0.188-0.678, p=0.002), and laparoscopic surgery rather than laparotomy (B: 1.585, OR: 4.879, 95% CI: 1.029-23.133, p=0.046) for spontaneous conception. CONCLUSIONS: The size, number and bilaterality of the endometrioma did not affect the spontaneous conception likelihood following surgical removal. However, increasing age and recurrence are negatively associated with the likelihood of spontaneous conception. Laparoscopic surgery may increase the chance of spontaneous conception when compared to laparotomy.

In Vitro Fertilisation and Intracytoplasmic Sperm Injection predictive factors: A review of the effect of female age, ovarian reserve, male age, and male factor on IVF/ICSI treatment outcomes.

The development of assisted reproductive technology has allowed offspring in infertile couples, and specifically, allowed infertile men to conceive through Intracytoplasmic Sperm Injection (ICSI). Despite the proven efficacy of In Vitro Fertilisation (IVF) and ICSI, many factors can influence its success. In this review we present an analysis on the effect of Female age, Ovarian Reserve, Male age and Male factor on the outcomes of IVF/ICSI, to determine if and which can be applied to the practical context. A literature search on PubMed, EMBASE and MEDLINE for relevant articles was elaborated until July 2021, leading to the selection of 234 articles based on their titles. After reading through the abstracts, those that evaluated IVF/ICSI predicting factors were selected. Finally, only those approaching female age, ovarian reserve, male age and male factor were considered in this review. Higher female age and baseline ovarian markers alterations such as lower anti-Müllerian hormone and antral follicular count, and higher basal follicle-stimulating hormone, were associated with poorer outcomes. The predictive value of Male age and Male factor presented varied results across literature. The multifactorial nature of male fertility makes evaluation difficult. Although the first assessment of male infertility is based on sperm concentration, motility and morphology, semen parameters have shown low prognostic value, whilst sperm DNA alterations gain importance. Nevertheless, results remain controversial. While some factors have proven to predict IVF/ICSI success, other need to be further studied to be applied to practical context to allow the best prognosis possible.

[Ovarian reserve and premature ovarian failure in girls and adolescents after hematopoietic stem cell transplantation]. / Reserva ovárica y falla ovárica prematura en niñas y adolescentes postrasplante de progenitores hematopoyéticos.

INTRODUCTION: The increased survival of children and adolescents after Stem Cell Transplantation (SCT) has allowed us to gain a better understanding of the late effects that this procedure might have. OBJECTIVE: to measure ovarian function and reserve after SCT. PATIENTS AND METHOD: A descriptive, observatio nal, and cross-sectional study of girls and adolescents with SCT between 1999 and 2011. External gynecologic examination, hormone tests, and abdominal gynecologic ultrasound were performed, observing pubertal development pre-SCT. The following data from the clinical record were recorded: baseline pathology, type of conditioning, use of radiotherapy in conditioning, age at the time of SCT, and history of acute or chronic graft-versus-host disease (GVHD). Hormonal tests included follicle- stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin (PRL), thyroid-stimula ting hormone (TSH), free thyroxine, total testosterone, sex hormone-binding globulin (SHBG), and anti-Müllerian hormone (AMH). Statistical analysis included the chi-square or Fisher's Exact test with a p-value < 0.05. RESULTS: 41 patients were evaluated. The median age at the time of SCT was 6.8 years (1.5-14.1) and the median age at evaluation was 14.8 years (range: 4-25.4 years). 93% of the transplants were in patients with oncological disease and with myeloablative conditioning regimens. All patients presented decreased ovarian reserve, and 72% showed Premature Ovarian Failure (POF). CONCLUSIONS: All patients had decreased ovarian reserve and most of them had a high prevalence of POF. Before SCT, a gynecological evaluation and subsequent follow-up for hormone monitoring and initiation of hormone replacement are essential.

[Assessment of ovarian reserve during gender affirmation hormone therapy in trans men]. / Evaluación de la reserva ovárica en varones trans durante el tratamiento hormonal de reafirmación.

Trans man is a biological female person with male gender identity, who can choose to receive a genderaffirming hormone treatment with testosterone. So far, the effects of this treatment on reproduction are unclear. Anti-müllerian hormone levels were evaluated in trans men during short-term testosterone treatment. A prospective study was conducted on 16 individuals who met the requirements to be included. The levels of gonadotrophins, estradiol, testosterone and antimüllerian hormone in the early follicular phase were measured prior to the start of the hormonal firming treatment, by means of a chemiluminescent method. The testosterone and antimüllerian hormone levels were determinedafter 6 to 12 months of treatment. The median age was 22.5 years.Basal testosterone and antimüllerian hormone levels of 0.58 ng/ml and 2.89 ng/ml respectively were obtained, values within the range corresponding to biological women. By the time of the semi-ünnual or annual control of the hormonal firming treatment, all the individuals managed to reach testosterone levels within the reference range of the male population (3-9 ng/ml). However, no significant differences were observed in antimüllerian hormone levels(p 0.7630) before and after 6 to 12 months of starting treatment with testosterone. Our study revealed that, despite the high biological variability of the antimüllerian hormone, no significant changes in its levels were observed during the firming hormone treatment in trans men.

Varón trans es aquella persona de sexo biológico femenino con identidad de género masculina que puede optar por recibir una terapia hormonal de reafirmación con testosterona. Hasta el momento, los efectos de este tratamiento sobre la reproducción son poco claros. Se evaluaron los niveles de hormona antimülleriana en varones trans durante el tratamiento con testosterona a corto plazo. Se realizó un estudio prospectivo en 16 individuos que cumplían los requisitos para ser incluidos. Se midieron los niveles de gonadotrofinas, estradiol, testosterona y hormona antimülleriana en fase folicular temprana, previo al inicio deltratamiento hormonal de reafirmación (basal), mediante un método quimioluminiscente, y luego de 6 a 12 meses de tratamiento se determinaron los niveles de testosterona y hormona antimülleriana (control). La mediana de edad fue 22.5 años. Se obtuvieron niveles de testosterona y hormona antimülleriana basales de 0.58 ng/ml y 2.89 ng/ml respectivamente, valores dentro del rango correspondiente a mujeres biológicas. Todos los individuos, al momento del control semestral o anual del tratamiento hormonal, lograron alcanzar niveles de testosterona dentro del rango de referencia poblacional masculino (3-9 ng/ml). Sin embargo, no se observaron diferencias significativas (p 0.7630) en los niveles de hormona antimülleriana basales y luego de 6 a 12 meses de iniciado el tratamiento con testosterona. Nuestro estudio reveló que, a pesar de la alta variabilidad biológica de la hormona antimülleriana, no se observaron cambios significativos en sus niveles durante el tratamiento hormonal de reafirmación en varones trans.

Ovarian Tissue Culture to Preserve Fertility in Transgender Male Patients after Hormonal Treatment / Cultura de tecido ovariano para preservação da fertilidade em pacientes transexuais masculinos após tratamento hormonal

Abstract Objective To evaluate the reproductive and histological characteristics of fresh cultured ovarian tissue from transgender male patients. Methods An in vitro pilot study in which samples were collected during sex reassignment surgery for transgender male patients. The ovarian cortex was cut into fragments of 2 mm, 3mm, and 4 mm, and placed in a 96-well plate suitable for cultivation at days 0, 2, 4, 6, and 8, when the histology was analyzed. Results Stromal hyperplasia was observed in all samples, and it was not associated with the obtainment of primordial or primary follicles. Peripheral reduction in cell count was also a recurrent finding. Primordial and primary follicles were identified with a heterogeneous pattern in fragments from the same patient and from different patients, and follicles in more advanced stages of development (secondary and antral) were not found. There was an association between the diameter of the ovarian fragments and the identification of primary follicles (p=0.036). The number of days in culture was associated with histological signs of tissue damaging in the fragments (p=0.002). The total number of follicles identified in the samples with 2mm in diameter was significantly lower than in those that measured 4mm in diameter (p=0.031). Conclusion A diameter of 4mm is suitable for ovarian tissue culture with the benefit of ease of handling. Even after prolonged exposure to testosterone, the ovarian fragments presented primordial and primary follicles, maintaining viability throughout the days they were exposed to the culture. Freezing the ovarian cortex of transgender patients who will undergo surgery for gender reassignment would be an interesting option, in the future, for the preservation of fertility.

Resumo Objetivo Avaliar as características reprodutivas e histológicas de tecido ovariano cultivado a fresco de pacientes transexuais masculinos. Métodos Estudo experimental in vitro e piloto, no qual amostras foram coletadas durante a cirurgia de redesignação de sexo para pacientes transexuais masculinos. O córtex ovariano foi cortado em fragmentos de 2mm, 3mm, e 4mm, e colocado em placa de 96 poços própria para cultivo nos dias 0, 2, 4, 6 e 8, quando a histologia foi analisada. Resultados Hiperplasia estromal foi observada em todas as amostras, e não esteve associada à obtenção de folículos primordiais ou primários. A redução periférica no número de células também foi um achado recorrente. Folículos primordiais e primários foramidentificados com padrão heterogêneo emfragmentos domesmo paciente e em fragmentos de pacientes diferentes, não sendo encontrados folículos em estágios mais avançados de desenvolvimento (secundários e antrais). Houve associação entre o diâmetro dos fragmentos ovarianos e a identificação dos folículos primários (p=0,036). O número de dias de cultura esteve associado a sinais histológicos de lesão tecidual nos fragmentos (p=0,002). O número total de folículos identificados nas amostras de 2mm de diâmetro foi significativamente menor do que nas de 4mm de diâmetro (p=0,031). Conclusão O diâmetro de 4mm parece ser mais adequado para a cultura de tecido ovariano com a vantagem de fácil manejo. Mesmo após exposição prolongada à testosterona, os fragmentos ovarianos apresentavam folículos primordiais e primários, e manteve a viabilidade ao longo dos dias de exposição à cultura. No futuro, o congelamento da cortical do ovário de pacientes transgêneros que se submeterão à cirurgia de redesignação sexual poderia ser uma opção interessante para a preservação da fertilidade.

Prevention of Premature Ovulation by Administration of Gonadotropin Releasing Hormone Antagonist the day After Ovulation Triggering in Diminished Ovarian Reserve Patients.

OBJECTIVE: The aim of the present retrospective study was to investigate the effectiveness of single-dose gonadotropin releasing hormone (GnRH) antagonist administration, the day after human chorionic gonadotropin (hCG) triggering for final oocyte maturation, on the prevention of premature luteinization in patients with diminished ovarian reserve in in-vitro fertilization (IVF) cycles. The secondary objective of the study was to search the effect of this protocol on pregnancy outcomes. METHODS: This is a retrospective study including 267 infertile patients who have single antral follicle seen with ultrasonography on the 2nd or 3rd day of the menstrual cycle before starting IVF treatment. We randomized patients into two groups. The case group comprised patients who had single-dose GnRH antagonist injection the day after hCG triggering formed, and the patients who had the standard treatment regime formed the control group. In both groups, the oocytes were collected 36 hours after hCG injection. RESULTS: The premature ovulation rate was significantly low in the case group compared with the control group (6.86 versus 20.6% per scheduled cycle) (p = 0.022). Also, the oocyte retrieval rate (93.14 versus 67.87% per scheduled cycle) (p = 0.013), the oocyte maturity rate (79.42 versus 47.87%) (p = 0.041), the fertilization rate (65.68 versus 34.54%) (p = 0.018), and the embryo transfer rate per scheduled cycle (44.11 versus 18.78%) (p = 0.003) were higher in the GnRH antagonist group than in the control group. CONCLUSION: The administration of GnRH antagonist the day after hCG trigger in IVF treatments of patients with diminished ovarian reserve enabled a significant decrease in the rate of premature ovulation but had no effect on live birth rate.

OBJETIVO: O objetivo do presente estudo retrospectivo foi investigar a eficácia da administração do antagonista do hormônio liberador da gonadotrofina (GnRH) em dose única no dia seguinte ao desencadeamento da gonadotrofina coriônica humana (hCG) para a maturação final do oócito, na prevenção da luteinização prematura em pacientes com diminuição do ovário reserva em ciclos de fertilização in vitro (FIV). O objetivo secundário do estudo foi pesquisar o efeito deste protocolo nos resultados da gravidez. MéTODOS: Trata-se de um estudo retrospectivo incluindo 267 pacientes inférteis que apresentam um único folículo antral visto por ultrassonografia no 2° ou 3° dia do ciclo menstrual antes de iniciar o tratamento de FIV. Nós randomizamos os pacientes em dois grupos. Os pacientes que receberam injeção de antagonista de GnRH em dose única no dia seguinte ao desencadeamento do hCG formaram o grupo caso, e os pacientes que receberam o regime de tratamento padrão formaram o grupo controle. Em ambos os grupos, os oócitos foram coletados 36 horas após a injeção de hCG. RESULTADOS: A taxa de ovulação prematura foi significativamente baixa no grupo caso em comparação com o grupo controle (6,86 versus 20,6% por ciclo programado) (p = 0,022). Além disso, a taxa de recuperação de oócitos (93,14 versus 67,87% por ciclo programado) (p = 0,013), a taxa de maturidade do oócito (79,42 versus 47,87%) (p = 0,041), a taxa de fertilização (65,68 versus 34,54%) (p = 0,018) e a taxa de transferência de embriões por ciclo programado (44,11 versus 18,78%) (p = 0,003) foram maiores no grupo antagonista de GnRH do que no grupo controle. CONCLUSãO: A administração de antagonista de GnRH, no dia seguinte ao desencadeamento de hCG em tratamentos de FIV de pacientes com reserva ovariana diminuída permitiu uma redução significativa na taxa de ovulação precoce, mas não teve efeito na taxa de nascidos vivos.

The Effect of Laparoscopic Endometrioma Surgery on Anti-Müllerian Hormone: A Systematic Review of the Literature and Meta-Analysis.

OBJECTIVE: This study aimed to assess the effect of endometrioma surgery on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels. METHODS: This systematic review and meta-analysis included observational studies and randomized clinical trials published in English referenced in MEDLINE, SCOPUS and Cochrane (1982-2019). We included studies that reported AMH levels in the pre and post-operative period of patients undergoing laparoscopic surgery for endometrioma. Preoperative AMH was defined as the baseline AMH; short term AMH was measured no later than a month after surgery; medium term AMH was measured between one and six months after surgery; and long-term AMH was measured six or more months after surgery. RESULTS: Thirty-six studies met the inclusion criteria. A significant decrease was observed in short, medium and long-term post-operative AMH levels when compared with baseline AMH. However, there were no differences between short and long-term post-operative AMH levels, suggesting a non-significant recovery after one year of follow-up. A significant decrease in post-operative AMH was observed in bilateral endometriomas compared with unilateral cases. In addition, patients with endometriomas presented a significant decline in post-operative AMH compared with patients with other benign ovarian conditions. The decrease in post-operative AMH was significantly greater in bilateral cystectomy when compared with vaporization with bipolar energy or laser. We also observed a greater decrease in post-operative AMH with bipolar energy hemostasis compared with suture and hemostatic agents. These results should be taken with caution due to the high heterogeneity of the studies analyzed. CONCLUSIONS: Endometrioma surgery has a deleterious effect on short, medium, and long-term post-operative AMH levels. Bilateral endometriomas and endometriomas greater than 7 cm have been associated with greater decreases in AMH. The mechanical resection of healthy tissue and the inflammatory damage on the ovarian cortex might explain the diminishing of ovarian reserve.