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.

Normal weight obesity is associated with lower AFC and adverse IVF outcomes.

Background: Body weight could be classified into underweight, normal weight and overweight according to percentage of body fat (%BF), and normal weight obesity (NWO) is defined as a normal BMI but a high %BF. While the impact of NWO in women fecundity remain unknow. Therefore, this study aimed to investigate the associations between %BF and reproductive outcomes among in vitro fertilization (IVF) women with normal BMI. Methods: A total of 469 women were included in this study and were classified into low %BF, normal %BF and high %BF according to previous study. Multivariate generalized regression models were employed to evaluate the associations of %BF with ovarian reserve parameters, IVF outcomes and early pregnancy outcomes. We further run sensitivity analyses by restricted the analysis to young women and those only with tubal factor, respectively. Results: About 32.2% of normal BMI women were misclassified according %BF, with 16.4% of them were low %BF and 15.8% were high %BF. The high %BF group had significantly lower antral follicle count (AFC) than normal %BF groups, and the AFC showed a tendency of decrease as %BF increased. In sensitivity analysis in young women, high %BF group also had significantly lower number of good-quality embryos when compared to normal %BF groups. The results expanded to all IVF outcomes when analysis restricted to tubal factor women. Conclusion: In summary, misclassifications of body weight status based on BMI are common according to %BF, and NWO is associated with adverse reproductive outcomes.

Relationships between antral follicle count and reproductive characteristics of embryo-recipient mares.

Mares (n = 77) were evaluated by antral follicle count (AFC) and selected as embryo recipients. Cyclic recipients received embryos between days 4-6 after ovulation. The acyclic recipients received an intramuscular (i.m.) protocol with 5mg of estradiol benzoate (EB) on the day of donor ovulation (D0; D-4 recipient), 3mg of EB on the following day (D1; D-3 recipient), and 3mg of EB (D2; D-2 recipient). Furthermore, 1500mg of progesterone (P4) i.m. given on D0 of the recipient (D4 donor) followed by 1500mg of P4 on the day of ET (D4-6 recipient). On the ET day, the AFC and animals' weight, body condition score (BCS), corpus luteum diameter, age and degree of uterine edema (UE) were measured. Pregnancy was confirmed on days 12 and 30. Low AFC was defined as ≤11 follicles (n = 43 mares) and high AFC as >11 follicles (n = 34 mares). Data were analyzed by a mixed effect model, including AFC group, reproductive seasonality, and season (P ≤ 0.05). UE was influenced (P = 0.05) by reproductive seasonality. The conception rate was higher (P = 0.016) in recipients with low (79.07 %) than high AFC (61.76 %) and higher (P = 0.005) in cyclic (81.40 %) than anestrus (58.82 %) mares. In addition, we observed a tendency (P = 0.06) for the interaction of AFC*reproductive seasonality, showing that high*anoestrus recipients had the lowest conception rate (37.50 %b) compared to high*cyclic (83.33 %a), low*anoestrus (77.78 %a) and low*cyclic (80 %a). The conception rate was higher in cyclic recipients with low AFC. Furthermore, UE was influenced by reproductive seasonality and mares in anestrus showed a higher degree of UE than cyclic mares.

Significance of serum AMH and antral follicle count discrepancy for the prediction of ovarian stimulation response in Poseidon criteria patients.

PURPOSE: To determine the risk of not being a poor responder in ovarian stimulation (OS) for in vitro fertilization (IVF) when ovarian reserve markers are discordant-one falling within Poseidon's criteria normal range (e.g., anti-Müllerian hormone (AMH) ≥ 1.2 ng/mL or antral follicle count (AFC) ≥ 5), and the other in the poor ovarian reserve range. METHODS: A tri-center retrospective cohort study (2015-2017) involving women with discordant AMH and AFC values undergoing their first IVF/ICSI cycle using conventional OS (cOS, ≥ 150 IU/day of follicle-stimulating hormone). Discordant serum AMH and AFC values were defined according to Poseidon's criteria (AMH < 1.2 ng/mL and AFC ≥ 5 or AMH ≥ 1.2 ng/mL and AFC < 5). Poor ovarian response (POR) was < 4 retrieved oocytes. Receiver operating characteristic (ROC) curves were used to determine AMH and AFC cut-offs for non-POR. Logistic regression analysis evaluated factors associated with non-POR. RESULTS: Out of 8797 patients who underwent assessment with both AMH and AFC, 1172 (13.3%) exhibited discordant values. Of these, 854 (72.9%) had ≥ 4 oocytes retrieved. Within this group, 726 (85.0%) had "low" AMH values, whereas 128 (15.0%) had "low" AFCs. An AFC of 6 had 77% sensitivity and 52% specificity (AUC = 0.700), while AMH of 1.19 ng/mL had 31% sensitivity and 85% specificity (AUC = 0.492) for non-POR. AFC and the use of recombinant gonadotropins were positive predictors of non-POR. CONCLUSIONS: When serum AMH is < 1.19 ng/mL, but AFC is ≥ 6, there is a moderate likelihood of a non-POR during stimulation. Conversely, if AFC is < 5 but serum AMH is ≥ 1.19 ng/mL, the chances of non-POR are low. Among patients with discordant markers, AFC emerges as the primary predictor of oocyte yield.

Impact of endometriosis on the ovarian follicles.

A significant body of evidence has supported a negative impact of endometriosis on ovarian follicles; however, the origin and relevance of this ovarian impairment in endometriosis is still a matter of debate. The ovarian damage can be caused by endometriosis itself or by surgeries aiming to remove endometriotic lesions. In this review, we summarized the existing knowledge on the mechanisms by which endometriosis can impact the ovarian follicles, from molecular to clinical points of view. From a molecular standpoint, the presence of endometriosis or its consequences can induce oxidative stress, inflammation, aberrant mitochondrial energy metabolism and inappropriate steroid production in granulosa cells, phenomena that may impair the quality of oocytes to variable degrees. These alterations may have clinical relevance on the accelerated exhaustion of the ovarian reserve, on the ovarian response to gonadotrophin stimulation in IVF cycles and on the competence of the oocytes. Critical points to be considered in current clinical practices related to fertility issues in endometriosis are discussed.

Reduced embryo yield obtained from superstimulated ewes with low circulating AMH concentration is improved by lengthening the FSH treatment.

The aim of the present study was to evaluate: 1) the association between AMH, AFC, superovulatory response and embryo yield in sheep; and 2) the effect of FSH treatment length during superstimulation of the first follicular wave on ovarian response and embryo yield, particularly in ewes with low and high AMH. The experiment was performed on 63 Polled Dorset ewes that received an ovarian superstimulatory treatment during the first follicular wave (Day 0 protocol). Ewes were administered a total dose of 240 mg of FSH distributed in six (6-dose regimen, n = 30) or eight (8-dose regimen, n = 33) decreasing doses administered 12 h apart. On Day -9 (random stage of the estrous cycle) and Day 0 (day of the first FSH dose) ovarian ultrasonography was performed and blood samples were collected for AFC and AMH determinations, respectively. A weak positive correlation between AMH and small AFC (follicles <4 mm) was observed (r = 0.23; P = 0.07), and AMH concentration was positively correlated (r = 0.29; P < 0.05) with the number of corpora lutea (CL) determined at embryo collection (i.e., 6 d after insemination). The length of FSH treatment tended (P = 0.06) to affect the ovarian response, such that the number of CL was greater in 8-dose than 6-dose treated ewes, while no differences (P > 0.10) in embryo yield outcomes were observed. For further analysis, ewes were classified into low (<7 ng/mL) and high (>10 ng/mL) serum AMH. In high AMH ewes, there were no differences (P > 0.05) in the number of CL nor embryo yield between the 6-dose and 8-dose treatment (e.g., 7.8 ± 2.4 and 8.3 ± 2.5 transferable embryos, respectively; P = 0.92). Conversely, for low AMH ewes, fertilized ova and embryo yield were greater (P ≤ 0.05) for ewes receiving the 8-dose than the 6-dose superstimulatory treatment (e.g., 8.4 ± 2.8 vs. 2.7 ± 0.9 transferable embryos, respectively, P ≤ 0.05). In conclusion, embryo production in poor responding ewes with low low circulating AMH is improved by extending the superstimulatory treatment length from 6 to 8 FSH doses.

Chapter 11. Endometriosis-related complications in women undergoing in-vitro fertilization.

As a chronic inflammatory disease, endometriosis generates fibrosis and anatomic distortion, which add extra-challenges to assisted reproductive technology cycles and requires a personalized approach. Patients with endometriomas have significantly decreased ovarian reserve and the ultrasound examination tends to be challenging, possibly underestimating follicle counts. It is crucial to assess the feasibility of oocyte retrieval procedure during the initial examination of the patient, as the distortion of the pelvic anatomy, the presence of hydrosalpinges and endometriomas might render the procedure difficult and increase the risk of complications. Possible injury to adjacent organs and risk of infection must be considered. Assisted reproductive technology seems to have limited or no impact on endometriosis recurrence, pain symptom progression or the size of endometrioma.

Effects of maternal antral follicle count in Bos taurus indicus cattle on the genetic merit of male offspring and antral follicle count of female offspring.

This study evaluated the effects of antral follicle count (AFC) in female cattle on offspring characteristics. Recently calved multiparous Bos indicus cows (Nelore; n = 222) were evaluated using ultrasonography on random days of their estrous cycle to determine the AFC and were classified into "low" (≤15 follicles), "intermediate" (≥16 and ≤ 29 follicles), and "high" (≥30 follicles) AFC groups. Weight and scrotal circumference (SC) of male offspring from these cows (n = 127) were determined from 20 to 27 months, and the data were added to a genetic evaluation program (economic total genetic merit, MGTe and TOP value) that uses the kinship matrix to evaluate the genetic relationship between animals. The AFC of female offspring from these cows (n = 95) was evaluated to analyze the relationship between the AFC of mothers and daughters. The effects of maternal AFC on the genetic merit of male and female offspring were analyzed using GLIMMIX and GLM, respectively. Correlations were assessed using the Pearson's coefficient. Male offspring of cows with high AFC had superior MGTe (P = 0.005) and TOP values (P = 0.01) than those from cows with low AFC. Additionally, the AFC of mothers was positively correlated with MGTe (R = 0.33; P < 0.0001) and negatively correlated with TOP values (R = -0.32; P < 0.0001). The SC (P = 0.01), but not body weight of the offspring (P = 0.46) was affected by maternal AFC. The daughters' AFC were correlated (R = 0.29; P = 0.004) with mothers' AFC and were influenced by maternal (P = 0.05) but not paternal (P = 0.77) effect. In conclusion, cows with high AFC produced males with greater MGTe, superior TOP values and higher SC. Maternal AFC did not influence the weight of male offspring but was correlated with the AFC of daughters.

Effect of SARS-CoV-2 infection and vaccine on ovarian reserve: A systematic review.

OBJECTIVE: To evaluate the effect of SARS-CoV-2 infection and vaccination on ovarian reserve. METHODS: Relevant articles were identified in the EMBASE, PubMed, and Web of Science databases from January 2020 to May 2023. Available clinical indicators of ovarian reserve, such as anti-Müllerian hormone (AMH), antral follicle count (AFC), follicle-stimulating hormone (FSH), and estradiol (E2), as well as the time interval from infection or vaccination to measurements, were assessed. RESULTS: Only 2 studies provided evidence that SARS-CoV-2 infection could damage ovarian function. In a comparison of the vaccinated and unvaccinated groups, although 1 prospective cohort study observed the transient statistically significant decrease on serum AMH levels at 3 or 6 months of follow-up, serum AMH levels remained within the normal reserve range (>1.1 ng/dl) throughout the study period. CONCLUSION: Overall, whether ovarian reserve may be affected by SARS-CoV-2 infection remains controversial and further investigations are warranted to clarify this issue. Based on the current evidence, it is safe to assume that COVID-19 vaccination does not exert any adverse effect on ovarian reserve parameters such as AMH, AFC, FSH, and E2, which will provide reassurance for women attempting to fall pregnant.

The Relationship Between Serum Anti-Müllerian Hormone and Basal Antral Follicle Count in Infertile Women Under 35 Years: An Assessment of Ovarian Reserve.

Introduction Estimating ovarian reserve has been the cornerstone of designing treatment plans for female infertility over the last few years. The most reliable biomarker for assessing female fertility is the antral follicle count (AFC). Also, the anti-müllerian hormone (AMH) is a sensitive test for predicting ovarian reserve and is precisely associated with AFC value. Objective The study aimed to investigate the relationship between serum AFC and AMH levels. Methods This cross-sectional type of observational study included 101 healthy infertile women aged 20-35 years and with low serum AMH. The mean difference in basal AFC among different age groups was evaluated using an independent sample t-test, revealing no significant difference. A multiple regression model was used to assess the association between serum AMH, and other factors related to demographics and other aspects of infertile women with basal AFC. Results The mean age of infertile women in our study was 30.7±3.69, and 29.7% of females had secondary infertility. The highest ovarian reserve was notable among the group 20-25 years, and the lowest follicular volume was observed in the 31 to below 35 years. Multiple regression analyses revealed that serum AFC and AMH had a strong positive association with basal ovarian volume. Additionally, every one-unit surge in AFC and AMH was statistically significant (p<0.05) and concomitant increases with 0.45 cc and 3.98 cc in basal ovarian volume, respectively. Conclusion The AMH and AFC strongly associate with basal ovarian volume, which declines as age progresses.

The association between Diet Quality Index-International score and risk of diminished ovarian reserve: a case-control study.

Introduction: Although limited evidence exists on the beneficial reproductive effects of diet quality indices, the association is still largely unknown. We aimed to investigate the association between Diet Quality Index-International (DQI-I) and antral follicle count (AFC) and serum antimullerian hormone (AMH) as precise and sensitive markers of ovarian reserve and to assess the risk of diminished ovarian reserve (DOR) in women seeking fertility treatments. Methods: In a case-control study, 370 women (120 women with DOR and 250 women with normal ovarian reserve as controls), matched by age and body mass index (BMI), were recruited. Dietary intake was obtained using a validated 80-item semi-quantitative food frequency questionnaire (FFQ). The quality of diets was assessed using DQI-I, which included four major dietary components: variety (0-20 points), adequacy (0-40 points), moderation (0-30 points), and overall balance (0-10 points). DQI-I score was categorized by quartiles based on the distribution of controls. AFC, serum AMH and anthropometric indices were measured. Logistic regression models were used to estimate multivariable odds ratio (OR) of DOR across quartiles of DQI-I score. Results: Increased adherence to DQI-I was associated with higher AFC in women with DOR. After adjusting for potential confounders, the odds of DOR decreased with increasing DQI-I score (0.39; 95% CI: 0.18-0.86). Conclusion: Greater adherence to DQI-I, as a food and nutrient-based quality index, may decrease the risk of DOR and improve the ovarian reserve in women already diagnosed with DOR. Our findings, though, need to be verified through prospective studies and clinical trials.

New insights into the role of LH in early ovarian follicular growth: a possible tool to optimize follicular recruitment.

Evidence shows that LH participates in enhancing transition from the early stage to the antral stage of folliculogenesis. It has been demonstrated that functional LH receptors are expressed, albeit at a very low level and even in smaller follicles, during the phase that was traditionally considered to be gonadotrophin independent, suggesting a role for LH in accelerating the rate of progression of non-growing and primary follicles to the preantral/antral stage. Hypogonadotropic hypogonadism, together with other clinical conditions of pituitary suppression, has been associated with reduced functional ovarian reserve. The reduction in LH serum concentration is associated with a low concentration of anti-Müllerian hormone. This is the case in hypothalamic amenorrhoea, pregnancy, long-term GnRH-analogue therapy and hormonal contraception. The effect seems to be reversible, such that after pregnancy and after discontinuation of drugs, the functional ovarian reserve returns to the baseline level. Evidence suggests that women with similar primordial follicle reserves could present with different numbers of antral follicles, and that gonadotrophins may play a fundamental role in permitting a normal rate of progression of follicles through non-cyclic folliculogenesis. The precise role of gonadotrophins in early folliculogenesis, as well as their use to modify the functional ovarian reserve, must be investigated.

Accuracy of ultrasound and visual inspection in antral follicular count in crossbred Holstein cows raised under grazing systems at high altitude.

The objective of this research was to investigate the diagnostic accuracy of post-mortem ultrasound in antral follicle count (AFC) determination and compare it with visual AFC in grazing crossbred Holstein cows, at high altitude in Ecuador. Pre-mortem blood from 80 cows was collected, and AFC and ovarian characteristics were analysed post-mortem by ultrasound and visual techniques. AFC counts were stratified as high, medium or low by terciles. Mean AMH concentration in pre-mortem blood was 280.1 ± 15.53 pg/mL. The AFC obtained by visual inspection (26.9 ± 9.49 follicles) was 23.8% higher than by ultrasound (20.5 ± 7.53 follicles) in all ovaries. Body condition score, age and weight of the cattle did not interact with the count technique. In the low AFC group, visual inspection and ultrasound provided similar AFC results. However, in the Medium- and High-AFC groups, AFC by ultrasound was 14.9% lower than AFC by visual inspection. We confirm that ultrasound can be used with great accuracy for AFC >3 mm (close to the resolution limit) in grazing crossbred Holstein cows at high altitude.

Age-Specific Nomograms for Antral Follicle Count in Fertile and Infertile Indian Women: A Comparative Study.

Objectives The aim of this study was to develop age-specific nomograms for antral follicle count (AFC) in fertile and infertile Indian women and (2) to compare the influence of age on AFC in both groups. Setting and Design It is a prospective cross-sectional study in a tertiary-care hospital in north-central India. Methods and Material One-thousand four-hundred seventy-eight fertile and 1,447 infertile women (primary infertility) of reproductive age (18-49 years) were recruited. One-thousand one-hundred eighty-one fertile and 1,083 infertile women fulfilled the selection criteria for the study. Transvaginal ultrasonography was done on the second or third day of the menstrual cycle. Statistical Analysis Age-specific nomograms for AFC were built for the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles in both groups. Correlation and regression analysis was done to estimate the relationship between the study variables. Statistical analysis was done by using IBM SPSS Statistics for Windows, version 20. Results At every age, each percentile value of AFC was lower in infertile than in fertile women. The decline of AFC with increasing age was linear in both fertile ( r = - 0.431, p < 0.001) and infertile ( r = - 0.520, p < 0.001) women; however, the rate was higher in the latter (0.50 follicle/year) than in former (0.44 follicle/year) group. The variation in AFC explained by age was 16.3% in fertile and 22.7% in infertile women. Conclusion AFC decreased linearly with advancing age in both fertile and infertile women, but more rapidly in the latter. The age only modestly explained the decline of AFC. The age-specific percentile thresholds for AFC should be used instead of age-independent constant thresholds in infertility counselling.

Factors Associated with Poor Ovarian Reserve in Young Infertile Women: A Hospital-based Cohort Study.

Background: In practice, we encounter many young infertile women with poor ovarian reserve though ovarian reserve starts to decline after 35 years of age. One of the established risk factors for poor ovarian reserve in young women is endometriosis. There are other conditions that are reported to be associated which require further research. Aims: We aimed to study the prevalence of poor ovarian reserve and to find out the associated factors in women who are <35 years of age. Settings and Design: This was a prospective observational cohort study conducted in a tertiary care setting. Materials and Methods: Women aged more than 21 years and <35 years without Polycystic Ovarian Syndrome (PCOS) or ovarian dysgenesis with normal male factor were included after ethical approval. The sample size was 166 and serum anti-Mullerian hormone (AMH) was estimated by immunoenzymatic assay and expressed in ng/ml. AMH ≤0.99 ng/ml was considered poor ovarian reserve. Apart from established risk factors, the proposed risk factors studied were age 31-35 years, presence of medical disorders, gynaecological pathology and history of repeated ovulation induction (OI). Statistical Analysis Used: Data were analysed by SPSS version 25. Chi-square test and Fisher's exact test were used to compare the variables between normal ovarian reserve and poor ovarian reserve. Risk estimation was done by logistic regression and was expressed in odds ratio (OR). Results: Poor ovarian reserve was diagnosed in 40% of this cohort, and 62% were between 31 and 35 years. After adjusting for age >30 years, women with endometrioma, hypothyroidism and prior history of ≥3 cycles of OI were found to be having poor ovarian reserve (OR was 5.7, 2.5 and 2.3, respectively). Conclusion: Poor ovarian reserve was present in 40% of young women, and significantly associated factors were hypothyroidism and history of repeated multiple OI. This could be a confounder for other underlying mechanisms driving early exhaustion of ovarian reserve in certain young women. Hence, along with established risk factors, these women should undergo AMH testing irrespective of age.

Analysis of the Effect of Female Genital Tuberculosis on Ovarian Reserve Parameters.

Background: Female genital tuberculosis (FGTB) is a known cause of female infertility. Worldwide incidence is 5%-10% and annual burden in India is around 4%-7%. It is known to cause tubal and endometrial damage. However, the effect on ovarian damage is poorly known. The availability of ovarian markers has contributed to an improved understanding of ovarian reserve in FGTB. Aims: The aim of this study was to assess ovarian reserve by measuring anti-Mullerian hormone (AMH) and antral follicle count (AFC) amongst infertile women and analyse the effect of GTB on ovarian reserve parameters. Settings and Design: This was a prospective study at a tertiary referral centre for infertility for 18 months. Materials and Methods: A total of 133 infertile women who underwent diagnostic hysterolaparoscopy and cartridge-based nucleic acid amplification test testing of an endometrial biopsy were included in the study. AMH and AFC of all the infertile women were assessed and compared between cases with and without FGTB. Statistical Analysis Used: Independent t-test was used to find the outcome differences in the distribution of values. P < 0.05 was considered statistically significant. Results: Fifty-eight (43.6%) cases were diagnosed with FGTB (Group I), and 75 (56.3%) cases were without FGTB (Group II). The mean AMH level 1.88 ng/ml (±1.52) and mean AFC 9.0 (±5.50) were significantly lower (P < 0.001) in Group I than in Group II with AMH 3.57 ng/ml (±2.93) and AFC 12.50 (±6.0). Conclusion: In women with prolonged infertility and low ovarian reserve, FGTB should be ruled out. Early diagnosis and treatment of GTB may prevent further decline of ovarian reserve and improve the reproductive outcome.

Predicting ovarian responses to the controlled ovarian hyperstimulation in elderly infertile women using clinical measurements and random forest regression.

During the past decades, the number of elderly infertile women is obviously increasing in China, and more and more of them are likely to seek medical assisted reproductive technologies. As the in vitro fertilization/embryo transfer (IVF/ET) treatment presents special medical and psychological challenges to elderly infertile women, it is extremely helpful to perform the clinical evaluation and outcome prediction regarding IVF/ET outcomes. In this study, we retrospectively collected 12 clinical measurements in prior to the oocyte recovery for 689 elderly infertile patients (≥35 years of old), and used for predicting ovarian responses to the controlled ovarian hyperstimulation based on random forest regression models. Using different predictor sets and 10-fold cross validation approach, the Mean Square Error (±standard deviation) of prediction models varied from 7.56 ± 0.31 to 13.90 ± 0.37 in the training datasets, and the correlation coefficients between observed and predicted values ranged from 0.86 ± 0.02 to 0.72 ± 0.05 in the testing datasets. Among all clinical measurements involved in this study, the preovulatory follicle count (PFC), antral follicle count (AFC), and anti-Müllerian hormone (AMH) were revealed to be the most important features in prediction models. In conclusion, we successfully established the machine learning approach that could help the elderly infertile patients to better understand the most possible outcomes in subjecting to the controlled ovarian hyperstimulation.

Self-made transvaginal ultrasound simulator: new training equipment in ultrasound evaluation of controlled ovarian stimulation and oocyte retrieval.

Aim: We sought to create and describe a self-made simulator designed and created for teaching purposes: a high-fidelity ultrasound phantom for demonstrating antral follicle count, ultrasound supervision of controlled of ovarian stimulation, and ultrasound-guided oocyte retrieval. Materials and methods: The uterus and ovaries of the ultrasound phantom were made from beef tongue, a male condom, latex gloves, cotton suture threads, bi-distilled water, and ultrasound gel. The components were placed in a pelvis created using three-dimensional (3D) printing. The phantom was presented to and evaluated by a group of 14 physicians pursuing a postgraduate course in reproductive medicine. Two training stations were structured: one to simulate antral follicle count and controlled ovarian stimulation and the other to simulate ultrasound-guided oocyte retrieval. Future specialists were requested to complete a feedback questionnaire evaluating the self-made simulator and the two practice stations. Results: The transvaginal ultrasound phantom was successfully created, making it possible to simulate antral follicle count, ultrasound control of ovarian hyperstimulation, and oocyte retrieval, and to capture ultrasound images. A review of the answers provided in the feedback questionnaire showed that the phantom had a good appearance and design, was realistic, helped to improve motor coordination, and could be a useful tool in the training of specialists in assisted reproduction. Conclusion: This phantom was designed to enable instruction and practice in the evaluation of ovarian follicles and ultrasound-guided oocyte retrieval in a supervised training environment. This self-made simulator is proposed as a training tool that could be included in the curricular structure of residency and postgraduate programs in reproductive medicine.

Comparison of anti-Müllerian hormone and antral follicle count in the prediction of ovarian response: a systematic review and meta-analysis.

BACKGROUND: Increasingly studies reported that the Anti-Müllerian hormone (AMH) seems to be a promising and reliable marker of functional ovarian follicle reserve, even better than the AFC test. Our study aimed to conduct a meta-analysis to assess the predictive value of AMH and AFC for predicting poor or high response in IVF treatment. An electronic search was conducted, and the following databases were used: PubMed, EMBASE, and the Cochrane Library (up to 7 May 2022). The bivariate regression model was used to calculate the pooled sensitivity, specificity, and area under the receiver operator characteristic (ROC) curve. Subgroup analyses and meta-regression also were used in the presented study. Overall performance was assessed by estimating pooled ROC curves between AMH and AFC. RESULTS: Forty-two studies were eligible for this meta-analysis. Comparison of the summary estimates for the prediction of poor or high response showed significant difference in performance for AMH compared with AFC [poor (sensitivity: 0.80 vs 0.74, P < 0.050; specificity: 0.81 vs 0.85, P < 0.001); high (sensitivity: 0.81 vs 0.87, P < 0.001)]. However, there were no significant differences between the ROC curves of AMH and AFC for predicting high (P = 0.835) or poor response (P = 0.567). The cut-off value was a significant source of heterogeneity in the present study. CONCLUSIONS: The present meta-analysis demonstrated that both AMH and AFC have a good predictive ability to the prediction of poor or high responses in IVF treatment.

Low ovarian reserve and risk of miscarriage in pregnancies derived from assisted reproductive technology.

STUDY QUESTION: Do low levels of anti-Müllerian hormone (AMH) or antral follicle count (AFC) properly predict miscarriage in young women conceiving with ART? SUMMARY ANSWER: Low ovarian reserve, as indicated by AMH or AFC, is not associated with miscarriage in young women conceiving with ART. WHAT IS KNOWN ALREADY: Presently, the impact of low ovarian reserve on the risk of miscarriage remains controversial. Some studies have reported an association between serum AMH levels and AFC and miscarriage, but others have failed to confirm these findings. The main limitation that undermines the reliability and consistency of the results is the confounding effect of female age. Indeed, after 35 years of age, on the one hand, the risk of miscarriage starts increasing because of impaired oocyte quality while, on the other, the physiological decline in AMH and AFC levels continues, thus hampering the possibility to properly explore the real effects of reduced ovarian reserve. Indeed, the two processes, i.e. the gradual loss of resting primordial follicles and the loss of oocyte quality, progress in parallel. In other words, the older the woman becomes, the higher is the risk of miscarriage, but one cannot distinguish between the effects of biological aging on oocyte quality and those mediated by a lower ovarian reserve. STUDY DESIGN SIZE DURATION: The present retrospective monocentric cohort study was carried out at Fondazione IRCSS Ca Granda Ospedale Maggiore Policlinico, Milan. All women referred to the ART Unit between 2014 and 2021 and who underwent either conventional IVF (c-IVF), ICSI, or IUI were reviewed. Only women younger than 35 were eligible because, up to this age, the risk of miscarriage is steady and not strictly related to age. PARTICIPANTS/MATERIALS SETTING METHODS: Women younger than 35 who achieved a singleton clinical pregnancy with c-IVF, ICSI, or IUI were selected. Women with patent causes of recurrent miscarriage were excluded, as well as those undergoing pregnancy termination for fetal or medical causes. Women who did and did not have a pregnancy loss before 20 weeks' gestation were compared. Detailed information was obtained from charts of the consulting patients. ART procedures were performed according to the standardized policy of our Unit. All women underwent serum AMH measurement and a transvaginal assessment of AFC prior to initiation of treatment. AMH levels were measured by a commercially available ELISA assay. To assess AFC, all identifiable antral follicles 2-10 mm in diameter at ultrasound were recorded. The primary outcome was the risk of miscarriage for women with serum AMH levels below 5 pmol/l. MAIN RESULTS AND THE ROLE OF CHANCE: There were 538 women were included, of whom 92 (17%) had a miscarriage. The areas under the ROC curves for prediction of miscarriage based on AMH levels and AFC were 0.51 (95% CI: 0.45-0.58) and 0.52 (95% CI: 0.45-0.59), respectively. The odds ratio (OR) of miscarriage for women with serum AMH levels below 5.0 pmol/l was 1.10 (95% CI: 0.51-2.36); the adjusted OR was 1.12 (95% CI: 0.51-2.45). Analyses were repeated considering other thresholds for AMH (2.9, 3.6 and 7.9 pmol/l) and for AFC (thresholds of 7 and 10). No associations emerged. LIMITATIONS REASONS FOR CAUTION: The retrospective design of the study hampered the collection of more precise but potentially relevant clinical information of the couples. We did not exclude women suffering from PCOS, a condition possibly associated with miscarriage. Moreover, the baseline characteristics of women who did and did not have a miscarriage differed in some characteristics. Thus, we adjusted the OR using a multivariate analysis, but we cannot fully exclude residual confounding effects. Finally, our results cannot be inferred to women older than 35. The mechanisms causing premature exhaustion of ovarian reserve may be different in younger and older women and this may lead to a different impact on the risk of miscarriage. WIDER IMPLICATIONS OF THE FINDINGS: Women embarking on ART with low ovarian reserve should be informed of their likely poor response to ovarian stimulation but can be reassured that, if conception occurs, their risk of miscarriage is not increased. STUDY FUNDING/COMPETING INTERESTS: This study was partially funded by Italian Ministry of Health-Current research IRCCS. E.S. reports grants from Ferring and honoraria for lectures from Merck-Serono and Gedeon-Richter. All the other authors do not have any competing interest to declare. TRIAL REGISTRATION NUMBER: N/A.