Impaired embryo development potential associated with thyroid autoimmunity in euthyroid infertile women with diminished ovarian reserve.

Purpose: The aim of this study was to evaluate the associations of thyroid autoimmunity (TAI) with the number of oocytes retrieved (NOR), fertilization rate (FR), and embryo quality (EQ) in euthyroid women with infertility and diminished ovarian reserve (DOR). Methods: This retrospective cohort study involved 1,172 euthyroid women aged 20-40 years with infertility and DOR who underwent an oocyte retrieval cycle. TAI was diagnosed in the presence of serum thyroperoxidase antibody (TPOAb) concentrations higher than 34 IU/ml and/or serum thyroglobulin antibody (TgAb) concentrations exceeding 115.0 IU/ml. Among these women, 147 patients with TAI were classified as the TAI-positive group, while 1,025 patients without TAI were classified as the TAI-negative group. Using generalized linear models (GLMs) adjusted for confounding factors, we evaluated the associations of TAI and the serum TPOAb and TgAb concentrations and NOR, FR, and EQ in this study's subjects. The TPOAb and TGAb values were subjected to log10 transformation to reduce skewness. Logistic regression models were used to estimate the effects of TPOAb and TgAb concentrations on the probabilities of achieving a high NOR (≥7) and high FR (>60%). Results: For the whole study population, women with TAI had a significantly lower NOR and poorer EQ than women without TAI (P < 0.001 for both). Interestingly, in the TSH ≤2.5 subgroup, the TAI-positive group also had a significantly lower NOR and poorer EQ than the TAI-negative group (P < 0.001 for both). Furthermore, negative associations were observed between log10(TPOAb) concentrations and NOR and the number of high-quality embryos and available embryos (P < 0.05 for all). The log10(TgAb) concentrations were inversely associated with NOR and the number of high-quality embryos (P < 0.05 for all). In the regression analysis, the log10(TPOAb) concentrations had lower probabilities of achieving a high NOR [adjusted odds ratio (aOR): 0.56; 95% confidence interval (95% CI) 0.37, 0.85; P = 0.007]. Conclusions: TAI and higher TPOAb and TgAb concentrations were shown to be associated with reductions in the NOR and EQ in the study population. Our findings provide further evidence to support systematic screening and treatment for TAI in euthyroid women with infertility and DOR.

The association between leptin, adiponectin levels and the ovarian reserve in women of reproductive age.

Background: Reproduction ability requires a certain amount of body fat that is necessary for ovulation, menstruation and pregnancy. Fat tissue represents an endocrine organ with high metabolic activity as it produces adipokines such as leptin and adiponectin. Our aim is to examine potential associations between women of reproductive age's ovarian reserves and their levels of leptin and adiponectin. Method: 74 women between 19 and 40 years of age consented to take part. Based on the patterns of their ovarian reserves, the women were divided into three main groups: women with adequate ovarian reserves (AOR - Group A, n=30), women with polycystic ovary syndrome (PCOS - Group B, n=31) and women with depleted ovarian reserves (DOR - Group C, n=13). Among these groups, several biochemical and demographic parameters were statistically compared. Results: Compared to the other two groups, women with DOR had statistically higher age and follicle stimulation hormone (FSH) levels. For estradiol (E2) and thyroid-stimulating hormone (TSH), no statistically significant difference was seen between the groups. In addition, women with PCOS had higher body mass index (BMI), luteinizing hormone (LH), total testosterone (TT), 17 hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), anti-Mullerian hormone (AMH), and antral follicle count (AFC) than the other two groups. In line with expectations, women with DOR also had lower levels of AMH and AFC than the other two groups. Women with PCOS had higher leptin levels than the other two groups, but there was no statistically significant difference. Women with PCOS had lower levels of adiponectin than the other groups, however the difference was not statistically significant. Conclusion: The way we classified women in our study according to their ovarian reserves is completely consistent with what has been published internationally. The ovarian reserve in women of reproductive age is not strongly correlated with leptin and adiponectin levels. For safe conclusions, more research including a greater number of samples is required.

The role of age and AMH on cumulative live birth rates over multiple frozen-thawed embryo transfer cycles: a study based on low prognosis patients of POSEIDON 3 and 4 groups.

BACKGROUND: Among the POSEIDON criteria, group 3 and group 4 have an expected low prognosis. For those patients with inadequate ovary reserve, embryo accumulated from consecutive oocyte retrieval cycles for multiple frozen-thawed embryo transfers (FET) has become more common. It is necessary to inform them of the pregnancy outcomes after single or multiple FET cycles before the treatment. However few studies about cumulative live birth rate (CLBR) for those with low prognosis have been reported. METHODS: This retrospective study included 4712 patients undergoing frozen embryo transfer cycles from July 2015 to August 2020. Patients were stratified as POSEIDON group 3, group 4, control 1 group (< 35 years) and control 2 group (≥ 35 years). The primary outcome is CLBRs up to six FET cycles and the secondary outcomes were LBRs per transfer cycle. Optimistic approach was used for the analysis of CLBRs and the depiction of cumulative incidence curves. RESULTS: Under optimistic model analyses, control 1 group exhibited the highest CLBR (93.98%, 95%CI 91.63-95.67%) within 6 FET cycles, followed by the CLBR from women in POSEIDON group 3(92.51%, 95%CI 77.1-97.55)was slightly lower than that in control 1 group. The CLBR of POSEIDON group 4(55% ,95%CI 39.34-70.66%)was the lowest and significantly lower than that of control 2 group(88.7%, 95%CI 80.68-96.72%). Further, patients in POSEIDON group 4 reached a CLBR plateau after 5 FET cycles. CONCLUSIONS: The patients of POSEIDON group 3 may not be considered as traditional "low prognosis" in clinical practice as extending the number of FET cycles up to 6 can archive considerably CLBR as control women. While for the POSEIDON group 4, a simple repeat of the FET cycle is not recommended after four failed FET cycles, some strategies such as PGT-A may be beneficial.

Dietary acid load and risk of diminished ovarian reserve: a case-control study.

BACKGROUND: The epidemiologic evidence on the association between acid load potential of diet and the risk of diminished ovarian reserve (DOR) is scarce. We aim to explore the possible relationship between dietary acid load (DAL), markers of ovarian reserve and DOR risk in a case-control study. METHODS: 370 women (120 women with DOR and 250 women with normal ovarian reserve as controls), matched by age and BMI, were recruited. Dietary intake was obtained using a validated 80-item semi-quantitative food frequency questionnaire (FFQ). The DAL scores including the potential renal acid load (PRAL) and net endogenous acid production (NEAP) were calculated based on nutrients intake. NEAP and PRAL scores were categorized by quartiles based on the distribution of controls. Antral follicle count (AFC), serum antimullerian hormone (AMH) and anthropometric indices were measured. Logistic regression models were used to estimate multivariable odds ratio (OR) of DOR across quartiles of NEAP and PRAL scores. RESULTS: Following increase in PRAL and NEAP scores, serum AMH significantly decreased in women with DOR. Also, AFC count had a significant decrease following increase in PRAL score (P = 0.045). After adjustment for multiple confounding variables, participants in the top quartile of PRAL had increased OR for DOR (OR: 1.26; 95%CI: 1.08-1.42, P = 0.254). CONCLUSION: Diets with high acid-forming potential may negatively affect ovarian reserve in women with DOR. Also, high DAL may increase the risk of DOR. The association between DAL and markers of ovarian reserve should be explored in prospective studies and clinical trials.

Associations between a normal-range free thyroxine concentration and ovarian reserve in infertile women undergoing treatment via assisted reproductive technology.

BACKGROUND: Some recent studies have shown that female subclinical hypothyroidism (SCH) is associated with diminished ovarian reserve (DOR). In this study, we aimed to investigate whether serum-free thyroxine (fT4) concentrations within the reference range are associated with ovarian reserve in women. METHODS: This cross-sectional study included 4933 infertile women with normal-range fT4 concentrations who received assisted reproductive technology treatment in our clinic. The data of women in different fT4 concentration tertiles (namely 12-15.33, 15.34-18.67, and 18.68-22 pmol/L) were compared with ovarian reserve markers, namely the anti-Müllerian hormone (AMH) concentration, the antral follicle count (AFC), and the number of aspirated oocytes. The primary outcomes were the AMH concentration and the risk of DOR, diagnosed as an AMH concentration < 1.1 ng/mL. RESULTS: The average ages of women in the low-normal, middle-normal, and high-normal fT4 tertiles were 33.20 (standard deviation [SD]: 5.11), 32.33 (SD: 5.13), and 31.61 (SD: 5.10) years, respectively (p < 0.0001). AMH concentrations (adjusted mean: 3.32 [95% confidence interval {CI}: 3.16 to 3.50] vs. 3.51 [3.40 to 3.62] vs. 3.64 [3.50 to 3.80] ng/mL, p = 0.022) were significantly different between the fT4 concentration tertiles. The risk of DOR was significantly increased in the low-normal (adjusted odds ratio: 1.61 [95% CI: 1.01 to 2.58]) and middle-normal (1.47 [95% CI: 1.00 to 2.16]) tertiles compared with the high-normal tertile. Subgroup analysis showed that AMH concentrations were significantly different among the fT4 concentration tertiles in women aged < 35 years (adjusted mean: 3.94 [95% CI: 3.70 to 4.20] vs. 4.25 [4.11 to 4.39] vs. 4.38 [4.18 to 4.58], p = 0.028), whereas this difference was not significant in women aged ≥ 35 years (p = 0.534). The general additive models using fT4 as a continuous variable indicated that a lower fT4 concentration within the normal range was significantly associated with a lower AMH concentration (p = 0.027), a lower AFC (p = 0.018), a lower number of aspirated oocytes (p = 0.001), and a higher risk of DOR (p = 0.007). CONCLUSION: Low-normal fT4 concentrations are associated with lower ovarian reserve in infertile women.

The impact of ovarian endometrioma and endometriotic cystectomy on anti-Müllerian hormone, and antral follicle count: a contemporary critical appraisal of systematic reviews.

Currently, three crucial questions regarding the reliability of ovarian reserve measures in women with ovarian endometrioma during the reproductive age are being discussed. Firstly, the effects of endometriotic cystectomy on short and long-term ovarian reserve. Secondly, the accuracy of serum anti-Müllerian hormone (AMH) and antral follicle count (AFC) in estimating ovarian reserve in these cases. Thirdly, the impact of endometrioma itself on the ovarian reserve over time in such cases. The purpose of the present review is to critically assess available systematic reviews and meta-analyses that have explored these questions. Nine eligible reviews were found following a systematic search on PubMed.com and similarly assessed. These reviews varied considerably regarding the level of evidence, as per an identical comprehensive scoring system. Moderate to high-quality evidence demonstrates that endometriotic cystectomy, by the stripping technique, adversely affects ovarian reserve in the short and long term, up to 9-18 months post-surgery. Damage to ovarian reserve was considerable but more pronounced in bilateral cases than unilateral cases, equivalent to 39.5% and 57.0%, respectively. Repeat endometriotic cystectomy is detrimental to ovarian reserve. The impact of endometrioma diameter on ovarian reserve before or after surgery is still unclear. Moderate to high-quality evidence, relying on simultaneous assessment of both ovarian reserve measures, shows that AMH is sensitive while AFC is not in cases undergoing ovarian cystectomy. AMH should be the biomarker of choice for counseling and managing women with endometrioma in their reproductive age, especially before surgery. While there is some evidence to show that endometrioma per se may harm ovarian reserve, this evidence is not robust, and there is good-quality evidence to challenge this notion. It is necessary to conduct further targeted RCTs, systematic reviews, and meta-analyses based on solid methodological grounds to increase the level of evidence, refine quantitative estimates, investigate open questions, and decrease heterogeneity.

Alkali and alkaline earth elements in follicular fluid and the likelihood of diminished ovarian reserve in reproductive-aged women: a case‒control study.

BACKGROUND: Imbalances in alkali elements (AEs) and alkaline earth elements (AEEs) cause reproductive disorders. However, it remains unclear whether AEs/AEEs in follicular fluid have a relationship with the serious reproductive disorder known as diminished ovarian reserve (DOR). METHODS: A nested case‒control study was carried out in China. Follicular fluid samples from 154 DOR patients and 154 controls were collected and assessed for nine AEs/AEE levels. Both the mixed and single effects of the elements on DOR were estimated with a Bayesian kernel machine (BKMR) and logistic regressions. RESULTS: The DOR group had higher median concentrations of Li, Na, and K in follicular fluid (all P values < 0.05). The logistic regression showed that compared with their lowest tertile, the high tertiles of K [OR:2.45 (1.67-4.43)], Li [OR: 1.89 (1.06-3.42)], and Cs [OR: 1.97 (1.10-3.54)] were significantly associated with the odds of DOR. The BKMR model reported that the DOR likelihood increased linearly across the 25th through 75th percentiles of the nine-AE/AEE mixture, while the AE group contributed more to the overall effect. CONCLUSION: This study revealed an association in which the likelihood of DOR increased with higher overall concentrations of AE/AEEs in follicular fluid. Among the nine detected elements, K, Li, and Cs exhibited significant individual associations with DOR. We provide new clues for the environmental factors on female fertility decline. TRIAL REGISTRATION: Retrospectively registered.

A new insight on evaluation of the fertility and pregnancy outcome in patients with primary Sjögren syndrome: a propensity score matched study in multi-IVF centers.

BACKGROUND: Primary Sjögren syndrome (pSS) is often related to adverse neonatal outcomes. But it's currently controversial whether pSS has an adverse effect on female fertility and clinical pregnancy condition. More importantly, it's unclear regarding the role of pSS in oocyte and embryonic development. There is a lack of comprehensive understanding and evaluation of fertility in pSS patients. OBJECTIVE: This study aimed to investigate oocyte and embryonic development, ovarian reserve, and clinical pregnancy outcomes in Primary Sjögren syndrome (pSS) patients during in vitro fertilization (IVF) treatment from multi-IVF centers. METHODS: We performed a muti-central retrospective cohort study overall evaluating the baseline characteristics, ovarian reserve, IVF laboratory outcomes, and clinical pregnancy outcomes between the pSS patients and control patients who were matched by Propensity Score Matching. RESULTS: Following PSM matching, baseline characteristics generally coincided between the two groups. Ovarian reserve including anti-müllerian hormone (AMH) and antral follicle counting (AFC) were significantly lower in the pSS group vs comparison (0.8 vs. 2.9 ng/mL, P < 0.001; 6.0 vs. 10.0, P < 0.001, respectively). The pSS group performed significant reductions in numbers of large follicles, oocytes retrieved and MII oocytes. Additionally, pSS patients exhibited obviously deteriorate rates of oocyte maturation, 2PN cleavage, D3 good-quality embryo, and blastocyst formation compared to comparison. As for clinical pregnancy, notable decrease was found in implantation rate (37.9% vs. 54.9%, P = 0.022). The cumulative live birth rate (CLBR) following every embryo-transfer procedure was distinctly lower in the pSS group, and the conservative and optimal CLBRs following every complete cycle procedure were also significantly reduced in the pSS group. Lastly, the gestational weeks of the newborns in pSS group were distinctly early vs comparison. CONCLUSION: Patients with pSS exhibit worse conditions in terms of female fertility and clinical pregnancy, notably accompanied with deteriorate oocyte and embryo development. Individualized fertility evaluation and early fertility guidance are essential for these special patients.

Serum levels of stem cell factor for predicting embryo quality.

We evaluated whether serum stem cell factor (s-SCF) levels just prior to ovulation induction could indicate the ability to develop a top-quality (TQ) blastocyst by day 5. We investigated patients with normal ovarian reserve (NOR), polycystic ovary syndrome (PCOS), diminished ovarian reserve (DOR), or mild endometriosis. Our pilot research suggests a correlation between s-SCF levels and the ability to form TQ blastocysts in patients with mild endometriosis. This significant statistical difference (p < 0.05) was noted between mild endometriosis patients for whom a TQ blastocyst was obtained and those for whom it was not possible, as measured on the 8th day of stimulation and the day of oocyte retrieval. The mean SCF levels in the serum of these women on the 8th day were at 28.07 (± 2.67) pg/ml for the TQ subgroup and 53.32 (± 16.02) pg/ml for the non-TQ subgroup (p < 0.05). On oocyte retrieval day it was 33.47 (± 3.93) pg/ml and 52.23 (± 9.72) pg/ml (p < 0.05), respectively.

Clinical factors associated with unexpected poor or suboptimal response in Poseidon criteria patients.

RESEARCH QUESTION: What clinical factors are associated with 'unexpected' poor or suboptimal responses to IVF ovarian stimulation per POSEIDON's criteria, and which AMH and AFC threshold values distinguish this population? DESIGN: Tri-centre retrospective cohort study (2015-2017) involving first-time IVF and ICSI cycles with conventional ovarian stimulation (≥150 IU/day of FSH). Eligibility criteria included sufficient ovarian reserve markers according to POSEIDON's classification (AMH ≥1.2 ng/ml; AFC ≥5). Ovarian response categories were poor (<4 oocytes), suboptimal (4-9 oocytes) and normal (≥9 oocytes). Primary outcomes included clinical factors associated with an unexpected poor or suboptimal response to conventional ovarian stimulation using logistic regression analyses, and the threshold values of AMH and AFC predicting increased risk of such responses using ROC curves. RESULTS: A total of 7625 patients met the inclusion criteria: 204 (9.3%) were poor and 1998 (90.7%) were suboptimal responders. Logistic regression identified significant clinical predictors for a poor or suboptimal response, including AFC, AMH, total gonadotrophin dose, gonadotrophin type and trigger type (P ≤ 0.02). The ROC curves indicated that AMH 2.87 ng/ml (AUC 0.740) and AFC 12 (AUC 0.826) were the threshold values predicting a poor or suboptimal response; AMH 2.17 ng/ml (AUC 0.741) and AFC 9 (AUC 0.835) predicted a poor response; and AMH 2.97 ng/ml (AUC 0.722) and AFC 12 (AUC 0.801) predicted a suboptimal response. CONCLUSIONS: The threshold values of AMH and AFC predicting 'unexpected' poor or suboptimal response were higher than expected. These findings have critical implications for tailoring IVF stimulation regimens and dosages.

Effectiveness of naturopathy for pregnancy in women with diminished ovarian reserve: feasibility randomized controlled trial.

RESEARCH QUESTION: Is conducting a randomized control trial (RCT) to assess the effectiveness of whole-system naturopathy in improving pregnancy rates among women with diminished ovarian reserve (DOR) feasible? DESIGN: A two-arm, parallel group, assessor-blinded feasibility RCT was conducted. Women with DOR, trying to conceive naturally or by ART, were randomly assigned to naturopathy plus usual care, or usual care alone for 16 weeks. Primary outcomes were feasibility (recruitment, adherence, retention rates), acceptability and safety. Secondary outcomes included ongoing pregnancy rates, live birth rates and health-related outcomes (mental health, quality of life, diet, exercise, sleep and weight). Statistical significance of the differences between the two groups (P-values) were exploratory. RESULTS: One hundred and fifteen women completed the screening survey between March and November 2022. Of these, 66 women were assessed for eligibility and 41 (62%) consented. Recruitment resulted in seven enrolments each month. All 41 participants (100%) adhered to the intervention, 38 (93%) completed end-point questionnaires, 32 (78%) found study participation to be acceptable and 18 out of 21 (86%) from the intervention group would recommend a naturopathic intervention to other women with DOR. The naturopathic treatment was associated with only mild and temporary adverse events. No between-group differences were observed for pregnancy and live birth rates. CONCLUSION: The evaluation of whole-system naturopathy through a RCT was feasible and the treatment was acceptable and well tolerated according to women with DOR. Outcomes from this study will help inform sample size calculations powered for fertility outcomes for future RCTs on this topic.

Poor ovarian response classification systems in the clinical setting - time for an update?

PURPOSE OF REVIEW: Poor ovarian response (POR) remains a key challenge to the success of assisted reproductive technology. Here, we offer a comprehensive review of the two main classification systems for POR, discussing their promises and pitfalls, evaluating their performance, and exploring potential avenues for improving upon these definitions of POR. RECENT FINDINGS: The Bologna criteria represented the first meaningful attempt to create a universal POR definition. Subsequently, the POSEIDON classification system was published to provide a more nuanced view of POR, classifying patients into four groups based on age and ovarian reserve markers. A recent study evaluated the likelihood of achieving at least one euploid embryo for transfer and found that, indeed, these classification systems are effective predictors of this outcome.While these criteria provide an effective counseling tool, several limitations - not considering underlying conditions, selecting somewhat arbitrary cutoffs, and evaluating the number of oocytes retrieved regardless of maturity - highlight the importance of improving upon these systems to create a more useful tool to more accurately predict ovarian response for clinical and research purposes. SUMMARY: In the era of personalized medicine, it is time to reconsider whether diagnostic criteria for a continuous metric such as ovarian response should be based on meeting all-or-nothing thresholds for specific parameters.

Association between neighborhood poverty and ovarian reserve: the ovarian aging study.

OBJECTIVE: This study aimed to examine the association between neighborhood poverty and ovarian reserve. METHODS: Among 1,019 healthy premenopausal women in the Ovarian Aging Study, aggregate exposure to neighborhood poverty was examined in relation to biomarkers of ovarian reserve, antimüllerian hormone (AMH) and antral follicle count (AFC). Specifically, the interaction of age-x-neighborhood poverty was assessed cross-sectionally to determine whether AMH and AFC declines across women may be greater in women exposed to more neighborhood poverty. Neighborhood poverty was assessed by geocoding and linking women's residential addresses in adulthood to US Census data. RESULTS: Independent of covariates, a significant interaction term showed the association between age and AMH varied by degree of exposure to neighborhood poverty in adulthood ( b = -0.001, P < 0.05). AMH declines increased progressively across women exposed to low, medium, and high levels of neighborhood poverty. In addition, main effects showed that higher neighborhood poverty was related to higher AMH in the younger women only ( b = 0.022, P < 0.01). Results related to AFC were all nonsignificant ( P > 0.05). CONCLUSIONS: Across women, greater aggregate exposure to neighborhood poverty in adulthood was related to lower ovarian reserve, indexed by AMH. In addition, there was a positive association between neighborhood poverty and AMH in younger women that attenuated in the older women. Together, results suggest that neighborhood disadvantage may have detrimental impacts that manifest as initially higher AMH, resulting in greater ovarian follicle loss over time. However, it remains unclear whether these results examining differences across women may replicate when AMH declines by neighborhood poverty are examined longitudinally.

Developmental programming of the ovarian reserve in livestock.

Mammalian females are born with a finite number of follicles in their ovaries that is referred to as the ovarian reserve. There is a large amount of variation between females in the number of antral follicles that they are born with, but this number is positively correlated to size of the ovarian reserve, has a strong repeatability within a female, and a moderate heritability. Although the heritability is moderate, numerous external factors including health, nutrition, ambient temperature, and litter size influence the size and function of the ovarian reserve throughout life. Depletion of the ovarian reserve contributes to reproductive senescence, and genetic and epigenetic factors can lead to a more rapid decline in follicle numbers in some females than others. The relationship of the size of the ovarian reserve to development of the reproductive tract and fertility is generally positive, although some studies report antagonistic associations of these traits. It seems likely that management decisions and environmental factors that result in epigenetic modifications to the genome throughout life may cause variability in the function of ovarian genes that influence fecundity and fertility, leading to differences in reproductive longevity among females born with ovarian reserves of similar size. This review summarizes our current understanding of factors influencing size of the ovarian reserve in cattle, sheep, and pigs and the relationship of the ovarian reserve to reproductive tract development and fertility. It provides strategies to apply this knowledge to improve diagnostics for better assessment of fertility and reproductive longevity in female livestock.

Understanding oocyte ageing.

Females are born with a finite and non-renewable reservoir of oocytes, which therefore decline both in number and quality with advancing age. A striking characteristic of oocyte quality is that "ageing" effects manifest whilst women are in their thirties and are therefore still chronologically and physically young. Furthermore, this decline is unrelenting and not modifiable to any great extent by lifestyle or diet. Since oocyte quality is rate-limiting for pregnancy success, as the proportion of good-quality oocytes progressively deteriorate, the chance of successful pregnancy during each 6-12-month period also decreases, becoming exponential after 37 years. Unlike oocyte quality, age-related attrition in the size of the ovarian reservoir is less impactful for natural fertility since only one mature oocyte is typically ovulated per menstrual cycle. In contrast, oocyte numbers are pivotal for in-vitro fertilization success, since larger numbers enable better-quality oocytes to be found and is important for buffering the inefficiencies of the IVF process. The ageing trajectory is accelerated in ~10% of women, so-called premature ovarian ageing, with ~1% of women at the extreme end of this spectrum with loss of ovarian function occurring before 40 years of age, termed premature ovarian insufficiency. The aim of this review was to analyze how ageing impacts the size and quality of the oocyte pool along with emerging interventions for combating low oocyte numbers and improving quality.

Impact of Ablation Versus Cystectomy for Endometrioma on Ovarian Reserve, Recurrence, and Pregnancy: An Updated Meta-Analysis.

This study aimed to compare the impact of ablation and cystectomy for ovarian endometrioma on ovarian reserve, recurrence rates, and pregnancy rates. Databases were searched for studies reporting ovarian reserve (measurement of anti-müllerian hormone [AMH] only), recurrence rates, and/or pregnancy rates after cystectomy and ablation for ovarian endometrioma. Six randomized clinical trials and five prospective cohort studies were included in this meta-analysis. All included studies had a low risk of bias. After ablation, weighted mean difference (WMD) between post- and pre-operative AMH values was - 0.40 (95% confidence interval [CI]: -0.61 to -0.19, p = 0.0002, I2 = 0%). After cystectomy, the WMD of AMH was - 1.08 (95% CI: -1.34 to -0.82, p < 0.00001, I2 = 48%). The intergroup comparison revealed that pre-operative AMH values were similar between the two groups, but post-operative AMH was significantly higher in the ablation group (WMD: 0.38, 95% CI: 0.13 to 0.63, p = 0.003, I2 = 3%). Subgroup analysis showed that the favorable effects of ablation compared to cystectomy are evident after three months of operation, in a bilateral setting, or with the laser ablation method. Overall recurrence rate (risk ratio [RR]: 1.51, 95% CI: 1.08 to 2.12, p = 0.02, I2 = 0%) and one-year recurrence rate (RR: 2.36, 95% CI: 1.30 to 4.31, p = 0.005, I2 = 0%) were significantly higher in the ablation group than in the cystectomy group. Pregnancy rates were similar between the two groups (odds ratio: 1.18, 95% CI: 0.92 to 1.52, p = 0.20, I2 = 72%). These results demonstrate that ablation could result in a smaller serum AMH decrement than cystectomy, but the recurrence rate could be higher after ablation.

Association of 'normal' early follicular FSH concentrations with unexpected poor or suboptimal response when ovarian reserve markers are reassuring: a retrospective cohort study.

RESEARCH QUESTION: Are basal FSH measurements, when elevated within its normal range, useful for assessing overall ovarian response and predicting unexpected poor or suboptimal ovarian response? DESIGN: Retrospective cohort study of ovarian stimulation cycles. RESULTS: A total of 1058 ovarian stimulation cycles (891 first, 167 repeated) were included. Anti-Müllerian hormone (AMH) values were categorized into four (0 to ≤0.6, >0.6 to ≤1.2, >1.2 to ≤3.0, >3.0 to ≤6.25 ng/ml) and basal FSH levels into four groups (<25th percentile: >3.5 to 6.1 IU/ml; 25-75th percentile: >6.1 to ≤8.5 IU/ml; >75-90th percentile: >8.5 to ≤9.9 IU/ml; >90th percentile: >9.9 to ≤12.5 IU/ml). Including only first cycles, a significant independent effect of basal FSH on retrieved cumulus-oocyte complex (COC) count was seen for all basal FSH categories (>90th, >75 to ≤90th, >25 to ≤75th compared with ≤25th percentile, P < 0.001, P = 0.001 and P = 0.007, respectively), when adjusted for age, body mass index (BMI), AMH, antral follicle count (AFC), starting dose and gonadotrophin type. Including only first cycles, patients aged 35 years or older with AFC of 5 or above and AMH 1.2 ng/ml or above, showed significantly higher odds of unexpected poor or suboptimal response if they had higher basal FSH values. Most prominently in the above 90th percentile group (OR 8.64, 95% CI 2.84 to 28.47 compared with <25th percentile) but lower categories (>25th to ≤75th percentile: OR 3.04, 95% CI 1.42 t 6.99; >75th to ≤90th percentile: OR 3.47, 95% CI 1.28 to 9.83 compared with ≤25th percentile) also showed a significant association after adjusting for age, AMH, BMI, AFC, dose, and gonadotrophin type. In patients with a second cycle, an increase in FSH levels in the second round compared with the first was associated with fewer retrieved COCs (estimate: -0.44, 95% CI -0.44 to -0.05, P = 0.027). This effect was adjusted for changes in age, FSH, AFC, starting dose, stimulation duration and change in medication type. CONCLUSIONS: Basal FSH is independently associated with overall ovarian response. Moreover, it is associated with unexpected poor or suboptimal response in patients, who would fulfill POSEIDON group 2 criteria after oocyte retrieval.

A systematic review of the association between modifiable lifestyle factors and circulating anti-Müllerian hormone.

BACKGROUND: Levels of anti-Müllerian hormone (AMH) are known to be associated with lifestyle determinants such as smoking and oral contraception (OC) use. When measuring AMH in clinical practice, it is essential to know which factors may influence circulating levels or ovarian reserve in general. OBJECTIVE AND RATIONALE: To date, there is no systematic review or summarizing consensus of the nature and magnitude of the relation between AMH and modifiable lifestyle factors. The purpose of this review was to systematically assess the evidence on association of lifestyle behaviors with circulating AMH levels. SEARCH METHODS: We performed a pre-registered systematic review of publications in Embase and PubMed on the lifestyle factors BMI, smoking, OC use, alcohol consumption, caffeine consumption, physical activity, and waist-hip ratio (WHR) in relation to circulating AMH levels up to 1 November 2023. The search strategy included terms such as 'Anti-Mullerian hormone', 'lifestyle', and 'women'. Studies were considered eligible if the association between at least one of the lifestyle factors of interest and AMH was assessed in adult women. The quality of included studies was assessed using the Study Quality Assessment Tools of the National Heart, Lung, and Blood Institute. The results were presented as ranges of the most frequently used association measure for studies that found a significant association in the same direction. OUTCOMES: A total of 15 072 records were identified, of which 65 studies were eligible for inclusion, and 66.2% of the studies used a cross-sectional design. The majority of studies investigating BMI, smoking, OC use, and physical activity reported significant inverse associations with AMH levels. For WHR, alcohol, and caffeine use, the majority of studies did not find an association with AMH. For all determinants, the effect measures of the reported associations were heterogeneous. The mean difference in AMH levels per unit increase in BMI ranged from -0.015 to -0.2 ng/ml in studies that found a significant inverse association. The mean difference in AMH levels for current smokers versus non-smokers ranged from -0.4 to -1.1 ng/ml, and -4% to -44%, respectively. For current OC use, results included a range in relative mean differences in AMH levels of -17% to -31.1%, in addition to a decrease of 11 age-standardized percentiles, and an average decrease of 1.97 ng/ml after 9 weeks of OC use. Exercise interventions led to a decrease in AMH levels of 2.8 pmol/l to 13.2 pmol/l after 12 weeks in women with polycystic ovary syndrome or a sedentary lifestyle. WIDER IMPLICATIONS: Lifestyle factors are associated with differences in AMH levels and thus should be taken into account when interpreting individual AMH measurements. Furthermore, AMH levels can be influenced by the alteration of lifestyle behaviors. While this can be a helpful tool for clinical and lifestyle counseling, the nature of the relation between the observed differences in AMH and the true ovarian reserve remains to be assessed. REGISTRATION NUMBER: PROSPERO registration ID: CRD42022322575.

Predictive Factors for the Formation of Viable Embryos in Subfertile Patients with Diminished Ovarian Reserve: A Clinical Prediction Study.

This study aims to construct and validate a nomogram for predicting blastocyst formation in patients with diminished ovarian reserve (DOR) during in vitro fertilization (IVF) procedures. A retrospective analysis was conducted on 445 DOR patients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) at the Reproductive Center of Yulin Maternal and Child Health Hospital from January 2019 to January 2023. A total of 1016 embryos were cultured for blastocyst formation, of which 487 were usable blastocysts and 529 did not form usable blastocysts. The embryos were randomly divided into a training set (711 embryos) and a validation set (305 embryos). Relevant factors were initially identified through univariate logistic regression analysis based on the training set, followed by multivariate logistic regression analysis to establish a nomogram model. The prediction model was then calibrated and validated. Multivariate stepwise forward logistic regression analysis showed that female age, normal fertilization status, embryo grade on D2, and embryo grade on D3 were independent predictors of blastocyst formation in DOR patients. The Hosmer-Lemeshow test indicated no statistical difference between the predicted probabilities of blastocyst formation and actual blastocyst formation (P > 0.05). These results suggest that female age, normal fertilization status, embryo grade on D2, and embryo grade on D3 are independent predictors of blastocyst formation in DOR patients. The clinical prediction nomogram constructed from these factors has good predictive value and clinical utility and can provide a basis for clinical prognosis, intervention, and the formulation of individualized medical plans.