Prenatal exposure to persistent organic pollutants and its impact on the ovarian reserve at 12 years old in the PELAGIE mother-child cohort.

Although the ovarian reserve is constituted in utero, the literature on the effects of persistent organic pollutants (POPs) during this vulnerable period on the ovarian reserve later in life is limited. We investigated whether cord blood concentrations of POPs were associated with decreased anti-Müllerian hormone (AMH, a marker of the ovarian reserve) levels in girls at the age of 12. We included 239 girls from the French mother-child PELAGIE cohort. POP concentrations of 14 organochlorine pesticides, 17 polychlorinated biphenyls (PCBs), 5 polybrominated diphenyl ethers, and 9 per-polyfluoroalkyl substances were measured on cord blood sampled at birth. During a follow-up study at 12 years old, blood samples were collected to measure AMH levels. Single-exposure associations were examined with multivariable linear regression models adjusted a priori for potential confounders. Stratification on menarche status was also performed. Mixture effects were investigated using quantile g-computation and Bayesian kernel machine regression. Overall, 16 POPs were measured in at least 30% of samples. No significant associations were found in multivariable linear regressions, except for the third tercile of exposure to PCB 180 which was statistically significantly associated with an increase in AMH levels at 12 years old (Tercile 2 v. Tercile 1: 0.13 ng/mL, 95% CI = -0.29, 0.56; Tercile 3 v. Tercile 1: 0.51 ng/mL, 95% CI = 0.02, 0.99). Additionally, in post-menarcheal girls (N = 104) only, the second tercile of p,p'-DDE was statistically significantly associated with decreased AMH levels at 12 years old (Tercile 2 v. Tercile 1: -0.61 ng/mL, 95% CI = -1.16, -0.05, Tercile 3 v. Tercile 1: 0.02 ng/mL, 95% CI = -0.51, 0.54). Both mixture models returned null associations. Despite the limited associations observed in this study, we recommend exploring these associations in larger mother-child cohorts and at older ages.

Associations between dietary patterns and parameters of ovarian reserve in Polish women of reproductive age.

OBJECTIVES: Research investigating the association between reproductive health and diet has predominantly focused on the antenatal and prenatal periods, as well as childbirth in women, and semen quality in men. There is a limited amount of research addressing female fertility assessed as ovarian reserve in relation to diet. The main aim of this study was to evaluate the association between dietary patterns and the parameters of ovarian reserve, such as antral follicle count (AFC), anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol (E2) - predictors of reproductive health in women of childbearing age. MATERIAL AND METHODS: Women aged 24-39 years (N = 511) were enrolled from fertility clinic in central Poland. The count of antral follicles was determined using ultrasonography (USG), FSH and E2 levels were measured using a chemilumi- nescence method and for determination of AMH level, an enzyme-linked immunosorbent assay method was employed. Diet was assessed according to food frequency questionnaire and dietary patterns were identified by factor analysis. Women were classified into 3 groups according to scores of each dietary pattern: Western, mixed, prudent. RESULTS: Higher adherence to the prudent dietary pattern in obese women was associated with significantly higher AFC (p = 0.03) and AMH (p = 0.05) as compared to participants with the Western dietary pattern. The results were adjusted for age, BMI, smoking and duration of fertility. Increased consumption of mixed dietary pattern was not statistically significant associated with any of examined ovarian reserve parameters. CONCLUSIONS: The prudent dietary pattern is positively associated with ovarian reserve in a cohort of women seeking fertility care. Continued research in this area will provide nutritional guidance for clinicians and their patients and provide novel insight on potential modifiable lifestyle factors which can be associated with ovarian reserve. Int J Occup Med Environ Health. 2024;37(4).

Mechanism study of YangJing ZhongYu decoction on regulating mitochondrial dynamics of ovarian granular cells and improving diminished ovarian reserve.

OBJECTIVE: Diminished ovarian reserve (DOR) encompasses both reproductive and endocrine disorders, resulting in a decline in female fertility. This paper explored the mechanism of Yangjing Zhongyu Decoction (YJZYD) regulating mitochondrial dynamics of ovarian granulosa cells (GCs) to improve DOR. METHODS: DOR patients were treated with YJZYD, with ovarian volume (OV), antral follicle count (AFC), and endometrial thickness (EMT) detected. C57BL/6 female mice were treated by cyclophosphamide (Cy) intraperitoneal injection and YJZYD solution daily gavage, with serum anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) levels determined. Ovarian GCs (KGN) were interfered with 4-Hydroperoxy-Cyclophosphamide (4-HC) and treated with the MAPK/ERK pathway inhibitor or activator. RESULTS: DOR patients showed increased levels of serum AMH, E2, OV, AFC and EMT, while reduced FSH and LH levels after YJZYD treatment. After Cy induction, DOR mice exhibited irregular estrous cycles, diminished serum AMH and E2 levels, elevated FSH and LH levels, reduced follicle number and atresia follicle number, disorderly arranged GCs, and severe interstitial fibrosis. After 4-HC treatment, KGN proliferation and Bcl-2, MFN1, and MFN2 were suppressed, while apoptotic rate, Bax, Cleaved-caspase-3, and p-Drp1 (Ser616) levels, and mitochondrial fission and quantity increased. YJZYD promoted 4-HC-treated KGN proliferation, boosted mitochondrial fusion, and inhibited apoptosis and mitochondrial fission via the MAPK/ERK pathway. CONCLUSION: YJZYD promoted ovarian GC proliferation and mitochondrial fusion, suppressed cell apoptosis and mitochondrial fission, and effectively improved DOR in mice by activating the MAPK/ERK pathway, providing a theoretical basis for the clinical application value of YJZYD in DOR treatment.

Conception vessel acupuncture research regularity in the treatment of diminished ovarian reserve: a multi-center, large-sample prospective cohort study protocol.

Background: Diminished ovarian reserve (DOR) refers to a decrease in the number or quality of oocytes in the ovarian cortex, which is a degenerative disease of the reproductive system, and can further develop into premature ovarian failure. There are few studies on acupuncture and moxibustion for DOR, which are still in the exploratory stage. Methods/design: This study was a real-world case registry study. According to whether the subjects received conception vessel acupuncture or not, they were divided into the basic treatment combined with conception vessel acupuncture group and the basic treatment group. A total of 1221 patients with DOR were enrolled and treated for 12 weeks. The percentage of patients with ≥30% improvement in anti-Müllerian hormone (AMH) was evaluated at the end of week 12. Secondary outcomes included Antral follicle count (AFC), modified Kupperman scale, basal FSH level, LH level, FSH/LH ratio, positive pregnancy, clinical pregnancy, early spontaneous abortion, ongoing pregnancy, and ectopic pregnancy. Discussion: This study provides clinical evidence and theoretical support for the treatment of DOR with conception vessel acupuncture and moxibustion, so as to guide and improve the efficacy of acupuncture and moxibustion. Trial registration: Acupuncture-Moxibustion Clinical Trial Registry ChiCTR2400080471. Registered on 30 January 2024.

Intraovarian PRP injection improves oocyte quality and early embryo development in mouse models of chemotherapy-induced diminished ovarian reserve.

Intraovarian injection of platelet-rich plasma (PRP) has been recently proposed, with encouraging results to provide an alternative option to patients diagnosed with POR or POI. However, the broad spectrum of PRP effects on the reproductive function and the mechanisms of action in follicular activation, response to stimulation, and embryo quality have not yet been studied. In this study, we first induced poor ovarian reserve (POR) and premature ovarian insufficiency (POI) ovarian phenotypes in CD1 mice undergoing PRP or sham intraovarian injection. PRP administration reduced those alterations induced by chemotherapy in ovarian stroma and follicle morphology in both the POR and POI conditions. After ovarian stimulation, we found that PRP did not modify the MII-oocyte yield. Nevertheless, the amount of obtained 2-cell embryos and fertilization rate were increased, being especially relevant for the POI model. Further in vitro embryo culture led to improved blastocyst formation rates and higher numbers of good quality blastocysts in PRP vs. sham females in both the POR and POI conditions. These positive results of PRP injection were also validated in the C57Bl/6 stain. Altogether, our findings suggest a possible effect on oocyte and embryo quality. This effect is likely due to the increase of local paracrine signaling through the released growth factors in PRP-treated ovaries.

Correlation of Follicle-stimulating Hormone, Anti-Mullerian Hormone, and Antral Follicle Count with Age in Ovarian Reserve Testing.

Objective: Ovarian reserve and hence ovarian response has a key role in assisted reproductive technology and predicting response to gonadotrophins in controlled ovarian hyperstimulation. Various tools, namely follicle-stimulating hormone (FSH), anti-Mullerian hormone (AMH), antral follicle count (AFC), estradiol, etc., have been studied to discover the best determinant of ovarian reserve. The aim of our study is to correlate different reproductive hormones with age of women to estimate ovarian reserve and to evaluate reliable marker for aiding infertility treatment. Materials and Methods: It is an observational study performed for 6 months, with 88 women (aged 21-39 years) having a complaint of infertility, enrolled in the infertility clinic of a tertiary care hospital. Baseline scan for AFC was done for every patient and their blood was sent for serum FSH, AMH analysis. Statistical procedures were employed to determine the association between age and reproductive hormones (i.e. FSH and AMH) as independent variables and AFC as a dependent variable. Results: A strong negative correlation was noted between FSH and AMH and between age and AMH (r = -0.492 and r = -0.498, respectively). A weak negative correlation was seen between AMH and total AFC (r = -0.241). A moderate positive correlation was seen on comparing age and FSH (r = 0.331), whereas no correlation was seen on comparing FSH with AFC and AMH with AFC. The presence of ovarian cyst did not affect AMH or AFC but reduced FSH values significantly. Conclusion: In the quest to determine a panel test for ovarian reserve testing we conclude, FSH and AFC should perform fairly in poor resource and low socioeconomic setting. The combination of FSH with AMH and AFC might aid in better determination of ovarian reserve in tertiary centers with available resources.

A Mega-Analysis of Anti-Müllerian Hormone Levels in Female Childhood Cancer Survivors Based on Treatment Risk, Time since Treatment, and Pubertal Status.

Purpose: Female childhood cancer survivors (CCSs) risk infertility due to gonadotoxic chemotherapy/radiation. Anti-Müllerian hormone (AMH) helps evaluate ovarian reserve, and the 2020 Oncofertility Pediatric Initiative Network (O-PIN) risk stratification is utilized to counsel risk of gonadal dysfunction/infertility. This study analyzed how AMH levels after cancer treatment differ with age and correlate AMH with O-PIN risk level and clinical outcomes. Methods: A literature review and mega-analysis of individual patient data were performed. Females ages 0-20 years at the time of cancer diagnosis with AMH values post-treatment were included. AMH outcomes were compared by O-PIN risk stratification, age at diagnosis, cyclophosphamide equivalent dose (CED), and hematopoietic stem cell transplant (HSCT). Multivariable random effects mixed models correlated AMH with diminished ovarian reserve (DOR), premature ovarian insufficiency (POI), and pregnancy. Results: In 13 studies with 608 CCSs, the median age (years) at diagnosis was 12.0 (interquartile range [IQR] 5.2-16.2) and 21.1 (IQR 17.1-30.0) at AMH measurement. AMH values were higher with time since treatment and correlated with the O-PIN risk level. Patients with HSCT had very low/undetectable AMH levels regardless of CED; when stratified by CED, AMH levels were lower if treated peripubertally or older. AMH was detectable in 54% (34/63) of patients with POI on hormone replacement. Pregnancy did not correspond to the gonadotoxicity risk level (p = 0.70). Conclusion: This study supports utilizing the O-PIN risk stratification system in estimating risk of DOR in CCSs and its categorization by pubertal status. AMH levels may return over time even after receiving the highest risk therapy. These findings may help counsel cancer patients pre- and post-therapy.

Anti-Müllerian hormone as a predictor of the number of oocytes obtained during in vitro fertilization treatments.

OBJECTIVE: To evaluate the correlation between serum anti-Müllerian hormone (AMH) and the number of oocytes retrieved after controlled ovarian stimulation for in vitro fertilization treatments and determine cut-off values predictive of poor and high response to stimulation. METHODS: It was performed a retrospective observational study that included 1003 cycles of controlled ovarian stimulation carried between February 2017 and December 2023 at a Medically Assisted Procreation Centre. The exclusion criteria were the following: serum AMH levels obtained more than 6 months prior to the start of the ovarian stimulation, the presence of a single ovary, non-Caucasian ethnicity, a controlled ovarian stimulation cycle performed for the purpose of oocyte donation or fertility preservation, a documented diagnosis of endometriosis, a documented history of ovarian surgery and the absence of essential data for the study in the medical records (absence of the number of oocytes obtained or the AMH value). Poor response to stimulation was defined as ≤ 3 oocytes retrieved, and high response was defined as > 15 oocytes. The correlation between variables was calculated using Spearman's correlation test and cut-off values were determined using ROC (Receiver Operating Characteristic) curves. RESULTS: AMH exhibited a significantly positive correlation with the number of oocytes retrieved (Spearman's correlation coefficient = 0.60, p<0.01). The predictive cut-off for poor ovarian response was 0.72 ng/mL (specificity of 95.13%, sensitivity of 43.23%), and the predictive cut-off for high ovarian response was 4.77 ng/mL (specificity of 89.86%, sensitivity of 38.22%). CONCLUSIONS: Serum AMH proved to be a good predictor of the ovarian response to controlled ovarian stimulation for in vitro fertilization treatments, which makes it useful in supporting clinical decision-making. However, it should not be used as an absolute discriminator of poor or high ovarian response.

Which side of the coin are you on regarding possible postnatal oogenesis?

It is well known that oocytes are produced during fetal development and that the total number of primary follicles is determined at birth. In humans, there is a constant loss of follicles after birth until about two years of age. The number of follicles is preserved until the resumption of meiosis at puberty and there is no renewal of the oocytes; this dogma was maintained in the last century because there were no suitable techniques to detect and obtain stem cells. However, following stem cell markers, several scientists have detected them in developing and adult human ovarian tissues, especially in the ovarian surface epithelial cells. Furthermore, many authors using different methodological strategies have indicated this possibility. This evidence has led many scientists to explore this hypothesis; there is no definitive consensus to accept this idea. Interestingly, oocyte retrieval from mature ovaries and other tissue sources of stem cells has contributed to the development of strategies for the retrieval of mature oocytes, useful for assisted reproductive technology. Here, we review the evidence and controversies on oocyte neooogenesis in adult women; in addition, we agree with the idea that this process may occur in adulthood and that its alteration may be related to various pathologies in women, such as polycystic ovary syndrome, premature ovarian insufficiency, diminished ovarian reserve and several infertility and genetic disorders.

Negative effects of ethanol on ovarian reserve and endometrium thickness: An animal study.

Objective: This study aimed to assess the effect of ethanol on the ovarian reserve and endometrium of rats by evaluating anti-Müllerian hormone (AMH) levels and follicle counts. Materials and Methods: We performed histological follicle counting and AMH measurements to evaluate ovarian reserve. The study included 16 Wistar albino rats evenly distributed into two groups of eight rats each. The rats in the intervention group (group 1) were administered ethanol at a daily dose of 2.5 g/kg via oral gastric lavage for 30 days, whereas the control group (group 2) received water as a placebo via oral gastric lavage for the same period. At the end of 30 days, the animals were sacrificed, and 2 mL blood samples were collected for AMH measurements. Laparotomy was performed to remove the ovaries and uterus. Results: Despite the lack of a meaningful distinction in the quantity of primordial and primary follicles between the two groups, a substantial disparity was observed in the overall follicle count and AMH levels. Specifically, the intervention group exhibited significantly lower total follicle counts and AMH levels than the control group (p≤0.001). The researchers also found that the endometrium of ethanol-treated rats was significantly thinner than that of control rats (p≤0.001). Conclusion: This study concluded that ethanol consumption can negatively affect reproductive ability and the success of in vitro fertilization treatment by reducing ovarian reserve and thinning the endometrium.

An overview of different methods to establish a murine premature ovarian failure model.

Premature ovarian failure (POF)is defined as the loss of normal ovarian function before the age of 40 and is characterized by increased gonadotropin levels and decreased estradiol levels and ovarian reserve, often leading to infertility. The incomplete understanding of the pathogenesis of POF is a major impediment to the development of effective treatments for this disease, so the use of animal models is a promising option for investigating and identifying the molecular mechanisms involved in POF patients and developing therapeutic agents. As mice and rats are the most commonly used models in animal research, this review article considers studies that used murine POF models. In this review based on the most recent studies, first, we introduce 10 different methods for inducing murine POF models, then we demonstrate the advantages and disadvantages of each one, and finally, we suggest the most practical method for inducing a POF model in these animals. This may help researchers find the method of creating a POF model that is most appropriate for their type of study and suits the purpose of their research.

Association between sleep quality and ovarian reserve in women of reproductive age: a cross-sectional study.

OBJECTIVE: To evaluate the association between sleep quality and ovarian reserve among women of reproductive age. DESIGN: Cross-sectional study SETTING: Not applicable. PATIENTS: A total of 1070 female participants aged 20-40 years enrolled from February 2023 to January 2024. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: A questionnaire was administered to the participants to collect baseline information related to reproductive and lifestyle factors. Pittsburgh Sleep Quality Index (PSQI) was used to measure sleep quality. Assessment was conducted on ovarian reserve, including total antral follicle count (AFC), anti-Müllerian hormone (AMH) level, and basal sex hormone level. RESULTS: The study sample of 1070 women had a mean age of 31.67 ± 4.41 years. A total of 314 participants (29.35%) were classified under the poor sleep group (PSQI score > 5).Significant differences were observed in the follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone(T),AFC, and AMH between the two groups (P < 0.05). The poor sleep group exhibited significantly lower levels of AMH and AFC (P < 0.01). The FSH levels in the poor sleep group were higher (P < 0.01).After the adjustment for confounding factors, multivariate regression analysis results indicated that the per-unit increase in PSQI score was associated with increased odds of diminished ovarian reserve (adjusted odds ratio [AOR] of 1.28 for AMH < 1.1 ng/ml, 95% confidence interval [CI]: 1.20- 1.37; AFC < 7, AOR: 1.34 ,95% CI: 1.25- 1.43;FSH ≥10mIU/mL,AOR:1.16 ,95%CI 1.08-1.25;AMH < 1.1 ng/ml or AFC < 7 or FSH ≥10mIU/mL, AOR: 1.29, 95%CI:1.22- 1.37). Compared with the PSQI ≤ 5 group, subjects with PSQI > 5 had increased odds of diminished ovarian reserve (odds ratio [OR]: 3.80, 95% CI: 2.82- 5.13; AOR: 4.43, 95% CI: 3.22-6.14). After stratification by age and body mass index (BMI), compared with the PSQI ≤ 5 group, all subgroups of the PSQI > 5 group had increased odds of diminished ovarian reserve, especially <35-year-old and BMI ≤ 18.4 kg/m2 subgroups. CONCLUSIONS: Poor sleep quality is associated with diminished ovarian reserve in women of reproductive age.

Can ultrasound elastography be useful in the diagnosis of poor ovarian response?

OBJECTIVES: This study aims to compare the elastographic properties of the ovaries of patients with poor ovarian response (POR) with healthy controls by using real-time ultrasound tissue elastography and to investigate the predictive value of ovarian strain ratio (OSR) in the diagnosis of POR. MATERIALS AND METHODS: A cross-sectional study was conducted among infertility patients. OSR measurements of 46 women diagnosed with POR and 41 healthy controls with male infertility were performed by real-time ultrasound tissue elastography. Ovarian volume, OSR, antral follicle count (AFC), age, body mass index (BMI), anti-mullerian hormone (AMH), follicle stimulating hormone (FSH), and estradiol (E2) values, were compared between the groups. A receiver operating characteristic curve was used to compare the sensitivity and specificity of OSR, AFC, AMH, FSH, and E2 for POR diagnosis. RESULTS: Patients with POR were significantly older, had a lower duration of infertility, lower AMH, higher FSH, higher E2, lower AFC and ovarian volume (p < 0.01, p = 0.02, p < 0.01, p < 0.01, p < 0.01, p < 0.01, p < 0.01, respectively). The mean OSR of both ovaries was similar between the groups. For the diagnosis of POR, the sensitivity and specificity for AMH were 97.5% and 100%, for AFC were 86.7% and 97.6%; for FSH were 66.7% and 80.5%, for E2 were 53.3% and 90.2%, respectively. CONCLUSIONS: The significant independent predictors of the POR were AMH, AFC, and FSH, with no additional significant contribution from OSR. However, considering the relationship between POR and ovarian fibrosis, it is recommended to investigate this issue in more comprehensive studies.

Immune checkpoint inhibitor treatment does not impair ovarian or endocrine function in a mouse model of triple negative breast cancer.

Background: Representing 15-20% of all breast cancer cases, triple negative breast cancer (TNBC) is diagnosed more frequently in reproductive-age women and exhibits higher rates of disease metastasis and recurrence when compared with other subtypes. Few targeted treatments exist for TNBC, and many patients experience infertility and endocrine disruption as a result of frontline chemotherapy treatment. While they are a promising option for less toxic therapeutic approaches, little is known about the effects of immune checkpoint inhibitors on reproductive and endocrine function. Results: Our findings in a syngeneic TNBC mouse model revealed that therapeutically relevant immunotherapies targeting PD-1, LAG-3, and TIM-3 had no effect on the quality and abundance of ovarian follicles, estrus cyclicity, or hormonal homeostasis. Similarly, in a tumor-free mouse model, we found that ovarian architecture, follicle abundance, estrus cyclicity, and ovulatory efficiency remain unchanged by PD-1 blockade. Conclusions: Taken together, our results suggest that immunotherapy may be a promising component of fertility-sparing therapeutic regimens for patients that wish to retain ovarian and endocrine function after cancer treatment.

Positive Effect of 25-Hydroxyvitamin D (25(OH)D) Levels in Follicular Fluid on Embryonic Developmental Potential in Diminished Ovarian Reserve (DOR) Patients Undergoing Microstimulation.

OBJECTIVE: This study aimed to explore the effect of 25-hydroxyvitamin D (25(OH)D) levels in follicular fluid (FF) on the embryo outcome with diminished ovarian reserve (DOR) patients undergoing in vitro fertilization (IVF) by microstimulation protocol. METHODS: A prospective cohort study of 79 patients with DOR who underwent IVF using the microstimulation protocol was conducted. Based on the level of 25(OH)D in follicular fluid (25(OH)D-FF), the patients were divided into a high-value group (25(OH)D-FF>11.1, n = 50) and a low-value group (25(OH)D-FF>11.1, n = 29). Correlation analysis was conducted between the level of 25(OH)D-FF and the rate of high-quality embryos on day 3 (D3). Logistic regression analysis of factors affecting the presence or absence of D3-available embryos in patients with DOR was conducted. RESULTS: The number of oocytes retrieved, mature oocytes (MII), normal fertilization rate, number of available embryos on D3, and high-quality embryo rate were lower in the low-value group than in the high-value group (p = 0.000, p = 0.000, p = 0.009, p = 0.000, p = 0.001). The clinical pregnancy rate of frozen embryo transfer (FET) between the two groups was no statistically significant difference (p > 0.05); correlation analysis between the 25(OH)D-FF level and the rate of high-quality embryos was performed using Spearman's rank-sum test, and there was a positive correlation (R = 0.271, P<0.01). Logistic analysis showed that 25(OH)D-FF level was a protective factor for embryonic outcome (odds ratio (OR) > 1, P<0.01). CONCLUSION: The 25(OH)D level in FF has a positive effect on embryonic outcomes in DOR patients with IVF using the microstimulation protocol. Vitamin D (VD) supplementation can be used to increase the number of available embryos and improve the quality of embryos for patients with DOR who are undergoing microstimulation of IVF.

Metabolic Risk in Patients with a Diminished Ovarian Reserve and Premature Ovarian Insufficiency.

Objective: Diminished ovarian reserve (DOR) and premature ovarian insufficiency (POI) represent conditions of different severity, characterized by an earlier-than-expected decrease in ovarian activity. The present study aims to compare metabolic disturbances between women with DOR and patients with POI from a different origin. Materials and methods: A total of 226 women (28 healthy women; 77 individuals with DOR, and 121 patients with POI/36 with Turner syndrome [TS] and 85 with non-TS POI/) have been studied retrospectively. Data concerning anthropometric indices, and metabolic parameters were collected. Results: Patients with DOR, non-TS POI, and TS had increased blood pressure and liver enzymes, pronounced insulin resistance, and worse lipid profiles than controls (p < 0.008 for all). TS patients had significantly higher ASAT, GGT, and TSH levels compared to non-TS POI and DOR individuals. The prevalence of type 2 diabetes tended to be higher in TS women compared to other groups. The prevalence of previously diagnosed polycystic ovarian syndrome was lower in the non-TS POI patients than in the DOR patients (p = 0.005). Conclusions: patients with decreased ovarian function suffer from insulin resistance, abnormal lipid profile, and subtle hepatic disturbances, irrespective of the severity of the condition and the presence of chromosomal aberrations.

Associations of bisphenol and phthalate exposure and anti-Müllerian hormone levels in women of reproductive age.

Background: In women, exposure to endocrine disrupting chemicals might accelerate the depletion of the ovarian reserve and might be associated with accelerative reproductive aging and fertility. We examined the longitudinal associations of exposure to bisphenols and phthalates with anti-Müllerian hormone concentrations. Methods: Pregnant women of 18 years or older that resided in Rotterdam between 2002 and 2006 were eligible for participation in this longitudinal prospective cohort study. We measured urinary bisphenol and phthalate concentration at three time-points in pregnancy among 1405 women, of whom 1322 women had serum Anti-Müllerian Hormone (AMH) measurements 6 and/or 9 years postpartum. We performed linear regression models to assess the association of urinary bisphenol and phthalate metabolites with AMH after 6 and 9 years, and linear mixed-effect model to assess the association with AMH over time. Models were adjusted for sociodemographic and lifestyle factors. Findings: In our multivariable linear regression models we observed associations of higher urinary pregnancy-averaged mono-isobutyl phthalate (mIBP), mono-(2-ethyl-5-oxohexyl) phthalate (mEOHP), and monobenzyl phthalate (mBzBP) with lower serum AMH after both 6 and 9 years. However, these associations did not remain after adjustment for multiple testing. No significant associations of bisphenol A with AMH were present in our study sample. In our linear mixed-effects models, higher mIBP, mono-(2-ethyl-5-hydroxyhexyl) phthalate (mEHHP), mEOHP, and mBzBP were associated with lower overall AMH levels (differences -0.07 (95% CI -0.13, -0.02), -0.09 (-0.15, -0.02), -0.08 (95% CI -0.14, -0.02), and -0.08 (-0.13, -0.03) µg/L per doubling in mIBP, mEHHP, mEOHP, and mBzBP respectively) (all False Discovery Rate adjusted p-values < 0.05). Interpretation: We identify decreases in indices of ovarian reserve in relationship to prenatal phthalate exposures. Studies are needed replicating our results among large multi-ethnic non-pregnant populations and assessing transgenerational effects of exposure on ovarian reserve. Funding: This study was supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organisation for Health Research and Development, the European Research Council, the Dutch Heart Foundation, the Dutch Diabetes Foundation, the European Union's Horizon 2020 Research and Innovation Program, the National Institutes of Health, Ansh Labs Webster, and the Royal Netherlands Academy of Arts and Sciences.

Evaluation of ovarian reserve and the assisted reproductive technology (ART) cycles' outcome as well as the relapse rate within one year after ART in women with multiple sclerosis: a case-control study.

OBJECTIVE: To compare the ovarian reserve and the results of infertility treatment, as well as to investigate the relapse rate in the first year after the assisted reproductive technology (ART) cycle in patients with multiple sclerosis (MS) referred to Royan Institute. MATERIALS AND METHODS: This retrospective study was carried out to evaluate all women diagnosed with MS and referred to Royan Institute for assessment and treatment of possible infertility between 2011 and 2022. The control group consisted of randomly selected healthy women with tubal factor infertility who were referred for treatment during the same time period and matched in terms of age. A comparison was made between groups in terms of ovarian reserve and infertility treatment outcomes. Additionally, patients with MS who met the criteria were monitored via telephone to evaluate the symptoms, disability and relapse rate both pre- and post-ART. RESULTS: Over the course of a decade, the database documented a total of 60 cases diagnosed with MS. Upon examination of the records, it was found that in 27 patients only admission was done without any hormonal assessment or infertility treatment cycle and 5 patients proceeded with the intrauterine insemination cycle. Eventually, 28 women with MS underwent the ART cycle and all of them were treated with interferon beta, glatiramer acetate, or some oral disease modifying therapies. No statistically significant difference in terms of the basal levels of luteinizing hormone, follicle-stimulating hormone and anti-Müllerian hormone was found between the MS and control groups (P > 0.05). Two groups were comparable in terms of menstrual status. The study revealed that both groups exhibited similarities in terms of the controlled ovarian stimulation protocol and duration, the dosage of gonadotropin administered, as well as the ovarian response type, clinical pregnancy rate, and live birth rate (P > 0.05). After follow up, only 2 patients (9.5%) reported relapse of symptoms within one year after ART. CONCLUSION: The ovarian reserve and ovarian stimulation cycle and pregnancy outcomes following the ART cycle in MS patients were similar to the age-matched control group. The relapse rate of multiple sclerosis did not show a significant increase within a year following the ART cycle.

Clinical evidence of coenzyme Q10 pretreatment for women with diminished ovarian reserve undergoing IVF/ICSI: a systematic review and meta-analysis.

BACKGROUND: To quantitatively evaluate the effect of coenzyme Q10 (CoQ10) pretreatment on outcomes of IVF or ICSI in women with diminished ovarian reserve (DOR) based on the existing randomized controlled trials (RCTs). METHODS: Nine databases were comprehensively searched from database inception to November 01, 2023, to identify eligible RCTs. Reproductive outcomes of interest consisted of three primary outcomes and six secondary outcomes. The sensitivity analysis was adopted to verify the robustness of pooled results. RESULTS: There were six RCTs in total, which collectively involved 1529 participants with DOR receiving infertility treatment with IVF/ICSI. The review of available evidence suggested that CoQ10 pretreatment was significantly correlated with elevated clinical pregnancy rate (OR = 1.84, 95%CI [1.33, 2.53], p = 0.0002), number of optimal embryos (OR = 0.59, 95%CI [0.21, 0.96], p = 0.002), number of oocytes retrieved (MD = 1.30, 95%CI [1.21, 1.40], p < 0.00001), and E2 levels on the day of hCG (SMD = 0.37, 95%CI [0.07, 0.66], p = 0.01), along with a reduction in cycle cancellation rate (OR = 0.60, 95%CI [0.44, 0.83], p = 0.002), miscarriage rate (OR = 0.38, 95%CI [0.15, 0.98], p = 0.05), total days of Gn applied (MD = -0.89, 95%CI [-1.37, -0.41], p = 0.0003), and total dose of Gn used (MD = -330.44, 95%CI [-373.93, -286.96], p < 0.00001). The sensitivity analysis indicated that our pooled results were robust. CONCLUSIONS: These findings suggested that CoQ10 pretreatment is an effective intervention in improving IVF/ICSI outcomes for women with DOR. Still, this meta-analysis included relatively limited sample sizes with poor descriptions of their methodologies. Rigorously conducted trials are needed in the future.

Potential damage to ovarian reserve from laparoscopic electrocoagulation in endometriomas and benign ovarian cysts: a systematic review and meta-analysis.

PURPOSE: Laparoscopic cystectomy for ovarian endometriomas and benign ovarian cysts is often conducted through hemostatic methods, with bipolar electrocoagulation as a common approach. This study evaluated the impact of electrocoagulation, primarily through bipolar energy, versus nonthermal hemostatic methods on ovarian reserve in patients undergoing laparoscopic cystectomy for ovarian endometriomas and benign ovarian cysts. METHODS: A systematic review with meta-analysis was conducted by searching the Cochrane Library, PubMed, EMBASE, and Web of Science databases. Randomized controlled trials (RCTs) comparing the impact of nonthermal hemostatic methods and electrocoagulation on the ovarian reserve during laparoscopic cystectomy were included. The Cochrane Risk of Bias Tool for Randomized Controlled Trials (ROB 2.0) was utilized to assess the quality of the included studies. The meta-analysis included 13 RCTs involving 1043 patients. Postoperative serum anti-Müllerian hormone (AMH) levels and antral follicle counts (AFCs) were analyzed using Review Manager ver. 5.4. RESULTS: Compared with the bipolar group, patients with endometriomas in the nonthermal hemostatic group exhibited significantly higher postoperative AMH levels at 1, 3, 6, and 12 months. Conversely, no significant differences in AMH levels were observed in patients with benign ovarian cysts. Similarly, AFCs showed no significant differences, except for lower postoperative AFCs in patients with endometrioma in the electrocoagulation group. CONCLUSION: Nonthermal hemostatic methods are associated with more effective preservation of the ovarian reserve compared with bipolar electrocoagulation in laparoscopic cystectomy for ovarian endometriomas. However, no significant impact of bipolar electrocoagulation on the ovarian reserve was observed in patients with benign ovarian cysts. TRIAL REGISTRATION: Registered in PROSPERO on April 10, 2023; ID # CRD42023413158.