AMH Concentrations Research Articles

P-698 The ULTRA trial: transvaginal ULTRAsound-guided ovarian ablation using May Health System in women with PCOS-related infertility: clinical and endocrine outcomes of first–in-human feasibility trial

Abstract Study question What is the feasibility of transvaginal ULTRAsound (TVUS)-guided ovarian ablation using the May Health System to improve ovulation, pregnancy, and hormonal abnormalities in PCOS-related infertility? Summary answer The feasibility of TVUS-guided ovarian ablation to improve ovulation, pregnancy, and hormonal abnormalities in PCOS-related anovulatory infertility was demonstrated. A pivotal study is underway. What is known already Laparoscopic ovarian drilling (LOD) is widely accepted as an effective second line treatment in PCOS-related infertility. However, laparoscopy is an invasive procedure that requires general anaesthesia and carries significant risks. Furthermore, there is no standardization of the LOD technique among surgeons. In contrast, the May Health System has been designed to deliver a precisely calculated amount of ovarian ablation via a less invasive route without general anaesthesia. This approach therefore transforms an invasive surgical procedure to an office-based technique similar in ovarian access to the well-established oocyte retrieval. Feasibility and safety results of this trial have previously been reported. Study design, size, duration This study included two feasibility, single-arm clinical trials running in parallel in the EU and US assessing the May Health System in performing TVUS-guided ovarian ablation in anovulatory PCOS women resistant to first-line ovulation induction drugs. Sample size was up to 35 participants with post-procedure follow-up (FU) of 24 months in EU and 12 months in US. Endpoints for this study were technical success, ovulation rates, pregnancy rates, and hormonal changes. Participants/materials, setting, methods Seven fertility centres participated in the trials. Participants were clomiphene/letrozole-resistant PCOS women aged 18-40 years. PCOS was diagnosed according to Rotterdam criteria. Participants underwent TVUS-guided ovarian ablation using the May Health System. The initial five participants underwent laparoscopy concurrent with TVUS-ablation. Post-procedure, serum progesterone was measured weekly until confirmation of ovulation or up to 12 weeks. Women were evaluated at 3 and 6 month, and then telephoned at 9- 12- and 24-month (EU sites only). Main results and the role of chance Thirty-one participants (mean±sd age, 31.9±3.3 years; BMI, 29.84.7kg/m2) underwent May Health TVUS-guided ovarian ablation and 25 completed at least six-months FU, with follow-up ongoing. Fourteen (45.2%) ovulated spontaneously within 3-months. Six more participants (19.3%) ovulated between three and nine months (after restarting CC/LTZ) giving a combined ovulation rate, with and without first-line medication restart, of 64.5% (20/31). Of the 31 participants who underwent the procedure, 10 (32%) have conceived to date, with seven live births, two ongoing, and one miscarriage. In 30 cases (97%), the targeted ablation was achieved successfully, while in one case (3%) the procedure was abandoned for the second ovary due to pain (n = 1). The median (IQR) serum AMH concentrations significantly decreased from baseline 76.1 (32.0, 210.7) to 62.5 (21.2, 253.6) pmol/l at 3-month (p = 0.001) and 56.7 (11.5, 126.8) pmol/l at 6-month (p = 0.001) post-procedure (Figure 2). The magnitude of post-ablation AMH decline was significantly (p = 0.047) greater in those who ovulated (responders) (-23.7% (-36.5, 17.7)) versus non-responders (-7.3% (-25.2, -1.6)). Ovarian volume significantly (p = 0.005) decreased from 13.6±5.1 ml at baseline to 10.1±3.7 ml at 6-month FU. There were no statistically significant changes in mean circulating testosterone, LH, or FAI at 3- or 6-month. Limitations, reasons for caution A limitation of this study is the lack of a comparator treatment / placebo arm. However, this was not necessary for this feasibility trial. It is possible to assume that the post-procedure ovulation and pregnancies could be compared for each participant with pre-procedure lack of ovulation and failure to conceive. Wider implications of the findings These data suggest that the investigational May Health System may offer an effective office-based second line ovulation inducing procedure for PCOS. The observed decline in circulating AMH, which was sustained for at least six months, could be the underlying mechanism of ovarian rebalancing that leads to subsequent resumption of ovulation. Trial registration number NCT03760926

Hormonal and Laboratory Profile of Polycystic Ovarian Syndrome (Pcos) Women Visiting Fertility Center in Indonesia

Our study aims to scrutinize the hormonal and laboratory profile of women with PCOS visiting a fertility center in Indonesia. A computerized database of 120 PCOS women and 120 controls was retrospectively reviewed and analyzed. According to analysis, the concentration of AMH and basal LH were significantly more elevated in the PCOS group than in the control group (6.77 vs. 2.05, P<0.001; and 6.8 vs. 5.3, P<0.001, respectively). The level of basal FSH was significantly lower in the PCOS group (5.83 vs. 7.86; P<0.001). After an IVF cycle, PCOS women had significantly higher retrieved oocytes and mature oocytes compared to controls (18 vs. 8, P<0.001; 12 vs. 6, P<0.001). The number of fertilizations, cleavages, and top-quality cleavages were also higher in the PCOS group than in the control group (10 vs. 4, P<0.001; 10 vs. 4, P<0.001; 4 vs. 2, P<0.001). At the blastocyst stage, patients with PCOS had a higher number of blastocysts and top-quality blastocysts than control (9 vs. 4, P<0.001); 4 vs. 1, P<0.01). However, the clinical pregnancy was significantly higher in the control group than in the PCOS group (52.6% vs. 16.7%; P = 0.045).

Serum concentration of anti-Müllerian hormone and its relationship with ovarian reserve in Brahman oocyte donors

Objetive. To evaluate the relationship of AMH blood concentration with ovarian follicular count and in vitro embryo production in female Brahman cattle. Material and methods. To standardize the AMH quantification for Brahman donors, experiment 1 was performed, blood samples were taken from 10 heat synchronized Brahman females, in three different days of the estrous cycle, with more than 90 days postpartum and with normal reproductive evaluation. Serum concentration of AMH was determined with a commercial immunoenzymatic kit. After the technique was standardized, blood samples were taken from 100 non-synchronized Brahman oocyte donors, an ovum pick-up session was performed for in vitro embryo production and the number of follicles greater than 2 mm in the two ovaries was registered. Results. There were no differences in AMH concentration between the evaluated days of estrous cycle and a correlation of 0.82 (p<0.001) was found between antral follicle population (AFP) and AMH concentration. Serum AMH concentration ranged from 0.02 to 2.69 ng/ml in Brahman oocyte donors. Also, a correlation of 0.73 (p<0.001) between AMH and AFP and 0.54 between the AMH and the percentage of blastocysts were found in donors. Conclusions. The AMH can be used as a satisfactory endocrine marker of ovarian reserve prediction for in vitro embryo production in Brahman cattle.

Hormone anti-müllérienne (AMH) en pédiatrie: établissement de valeurs de référence avec le dosage de l'AMH Fujirebio® Lumipulse G et comparaison avec le dosage Roche® Elecsys sur les mêmes échantillons pédiatriques

We performed a method comparison between the Fujirebio® Lumipulse G AMH assay and the Roche® Elecsys AMH assay using the same pediatric samples. We described full pediatric gender and age-specific reference ranges for AMH using the Fujirebio® AMH assay on the Lumipulse G 600 II. The study was performed on 281 plasma samples collected in tubes with lithium heparin. The samples were from patients (135 males and 146 females) aged from 3 days to 22 years collected at the University Hospital Center of Tours. The Fujirebio® Lumipulse method showed excellent correlation with Roche® Elecsys but had a significant proportional positive bias. The data were used to propose pediatric reference values adapted to the Fujirebio® method. Our study described full pediatric gender and age-related reference ranges for AMH using the Fujirebio® AMH assay on the Lumipulse G600II. The delineation between normal male and female AMH concentrations make them valuable clinical tools for the monitoring of pediatric sexual and reproductive development from early childhood through the pubertal transition into adulthood.

Investigation of serum anti-Müllerian hormone levels at follicular phase and interestrus period in queens

The objectives of this study were: i) to report overall mean AMH serum concentrations in queens, ii) to determine relationship between serum AMH concentration with estradiol level, iii) to investigate the relationship between serum AMH with follicular phase and interestrus phase of the estrous cycle, iv) to discuss the usability of AMH as a biomarker to diagnosis of ovarian remnant syndrome in breeding season in queens. In the study, 64 healthy queens referred to clinics for routine ovariohysterectomy were used. After anamnesis, vaginal cytology, macroscopic examination of the uterus and ovaries and estradiol measurement, queens were divided into two groups: follicular phase (n: 45) and interestrus (n: 19). Estradiol and AMH levels in serum samples were determined by ELISA. In the evaluation of serum AMH concentrations, a statistical difference was determined between the follicular phase and interestrus (P˂0.05). A negative correlation was found between age and estradiol in both follicular phase (r = -0.171) and interestrus (r = -0.385) groups. A positive correlation was found between age and AMH in the interestrus (P˂0.01, r = 0.696). Serum AMH levels in the interestrus were found to be significantly higher than follicular phase (P˂0.05). It was thought that this increase in serum AMH levels during the interestrus period, which is the stage where oocytes were selected for ovulation, may be an indicator of the role of AMH in oocyte selection in queens, as in many other mammalian species.

Progestin and adipoQ receptor 7 (PAQR7) mediate the anti-apoptotic effect of P4 on human granulosa cells and its deficiency reduces ovarian function in female mice

PurposePAQR7 plays a key role in cell apoptosis as a progesterone membrane receptor. The physiological mechanism of PAQR7 in ovarian function and its anti-apoptotic action in mammals remain poorly understood.MethodsWe first added 0.2 µM aminoglutethimide (AG), an inhibitor of endogenous progesterone (P4) secretion, and transfected siPAQR7 co-incubated with P4 in human KGN cells to identify granulosa cell apoptosis, respectively. Additionally, we used Paqr7 knockout (PAQR7 KO) mice to assess the role of PAQR7 in the ovary.ResultsThe PAQR7 deficiency significantly increased apoptosis of KGN cells, and this significant difference disappeared following P4 supplementation. The Paqr7−/− female mice showed a prolonged estrous cycle, reduced follicular growth, increased the number of atresia follicles, and decreased the concentrations of E2 and AMH. The litters, litter sizes, and spontaneous ovulation in the Paqr7−/− mice were significantly decreased compared with the Paqr7+/+ mice. In addition, we also found low expression of PAQR7 in GCs from human follicular fluids of patients diagnosed with decreased ovarian reserve (DOR) and ovaries of mice with a DOR-like phenotype, respectively.ConclusionsThe present study has identified that PAQR7 is involved in mouse ovarian function and fertilization potential. One possible mechanism is mediating the anti-apoptotic effect of P4 on GC apoptosis via the BCL-2/BAX/CASPASE-3 signaling pathway. The mechanism underlying the effect of PAQR7 on ovarian development and aging remains to be identified.

Lower serum AMH concentration is correlated with serum IgG1 decreased in the infertile woman: A real-world retrospective study

ObjectivesIn this real-world approach, we examined the serum Anti-Mullerian Hormone (AMH) level and the relationship with serum IgG subclass in the infertile women. MethodsA total of 574 female participants were recruited for this study. The serum AMH, IgG subclass(IgG1, IgG2, IgG3, IgG4) and immunoglobulin (Ig) G、IgM、IgA、IgE as well as complement C3, C4 were analyzed. The difference in serum AMH level was assessed according categorized as above or below the median of the ratio of serum IgG subclass(IgG1, IgG2, IgG3, IgG4) to total IgG (RIgG subclass/IgG). ResultsThe serum AMH level of the low RIgG1/IgG group is significantly decreased than that high RIgG1/IgG group (p < 0.05). The Spearman correlation analysis showed that the serum AMH level was significantly negatively correlated with age and significantly positively correlated with serum IgG1 levels respectively (p < 0.05). GLMMs multivariate model showed that after adjusting the covariate and possible mixed factors including age, serum immunoglobulin, complement C3 and C4, the serum AMH level was significantly positively correlated with IgG1 level (p < 0.01). ConclusionsDecreased serum IgG1 may significantly affect the ovarian reserve function of women. Confirmation of this association and elucidation of its underlying mechanisms are needed to place these results in a clinical perspective.

Endocrine and dog factors associated with semen quality

Knowledge of factors associated with semen quality may help in investigations of the aetiology and pathophysiology. We investigated the correlation between biomarkers for testicular cell function (anti-müllerian hormone, AMH, Inhibin B, testosterone, free androgen-index (testosterone/sex-hormone binding globulin), insulin like peptide 3, INSL-3), alkaline phosphate (ALP), canine prostate-specific esterase (CPSE), and heterophilic antibodies with dog variables, semen quality, and fertility. Blood and semen were collected from 65 Bernese Mountain Dogs. We evaluated total sperm count, motility and morphological parameters. The semen quality ranged from poor to excellent, with an average total sperm count of 1.1 × 109 and 50% morphologically normal spermatozoa (MNS). Age and abnormal testicular consistency correlated with decreased motility and MNS. Higher ALP correlated with higher total sperm count. AMH could not be detected in seminal plasma. AMH in blood correlated with head defects and high AMH concentration correlated with a severe decline in several semen parameters. Testosterone was negatively and CPSE positively correlated with age. No correlations were found for INSL-3, inhibin B, or heterophilic antibodies. Our findings contribute to the understanding of factors associated with semen quality in dogs, particularly related to Sertoli cell function.

Developmental programming of production and reproduction in dairy cows: III. Association of level of maternal milk production with offspring's birth weight, survival, productive and reproductive performance and AMH concentration from birth to the first lactation period

Although some studies investigated the relationship of dam milk production (DMP) with offspring birth weight and productive performance, limited information is available on the association of level of DMP with reproductive performance in dairy cows. Therefore, the present study was conducted to understand whether dams with various levels of milk production produce offspring with different fertility. In study I, offspring were classified based on the level of DMP into five categories, including DMP1 (dams with <10.00 × 103 kg of 305-day milk production), DMP2 (dams with ≥10.00 × 103 kg and <12.00 × 103 kg of 305-day milk production), DMP3 (dams with ≥12.00 × 103 kg and <14.00 × 103 kg of 305-day milk production), DMP4 (dams with ≥14.00 × 103 kg and <16.00 × 103 kg of 305-day milk production) and DMP5 (dams with ≥16.00 × 103 kg of 305-day milk production). In study I, data of birth weight, milk yield and reproductive variables of 14,536 offspring born to lactating dams and corresponding data of DMP were retrieved. In study II, blood samples (n = 339) were collected from offspring in various categories of DMP for measurement of serum AMH. Offspring were heavier at birth in DMP4 and DMP5 categories than DMP1 and DMP2 categories (P < 0.05). Milk yield of offspring increased as DMP elevated (P < 0.05); however, offspring in DMP1 and DMP2 categories produced higher milk as compared with their dams during primiparity (P < 0.05) whereas offspring in DMP3, DMP4 and DMP5 categories produced less milk as compared with their dams during primiparity (P < 0.05). Milk fat to protein ratio during the first month of lactation was greater in DMP4 and DMP5 categories than DMP1 category (P < 0.05). Offspring of DMP4 and DMP5 categories were inseminated and conceived at younger ages than offspring of DMP1 category during nulliparity (P < 0.05). Calving to conception interval was longer in DMP5 than DMP1 category in primiparous offspring (P < 0.05), but concentration of AMH did not differ among various categories of DMP (P > 0.05). In conclusion, dams with greater level of milk production produced heavier offspring with higher milk yield but worse transgenerational improvement in milk production and diminished reproductive performance, which were seemingly under higher pressure of negative energy balance during the first month of lactation.

Perfil sérico do hormônio anti-Mülleriano de touros Nelore na peripuberdade

ABSTRACT This study aimed to investigate the profile of AMH serum concentrations during the period of prepuberty in young bulls. The bulls were selected and evaluated for 150 days to assess their sexual development. The semen and blood collection, body weight (kg), and scrotal measurements were performed every 30 days, and puberty (D0) was considered when at least 50×106 spermatozoa/mL, and 10% of progressive motility were verified for the first time. After the blood collection, plasma was separated and used to determine the AMH concentration by ELISA, presenting values of 611.4a (±94.5), 555a (±181.99), 621.6ab (±133.44), 370.4ab (±59.36) and 51.7b (±7.94) for moments of -60, -30, 0, +30 and +60 of puberty, respectively. During the evaluated period, there was a progressive increase in body weight (kg), scrotal circumference (cm), and semen characteristics. The AMH mean plasma concentration decreased 60 days after puberty onset. There was no correlation with the andrological parameters analyzed; however, there was a positive and strong correlation between the testicular height and width at puberty onset with plasma concentrations of AMH. We concluded that AMH is not a helpful tool for the early prediction of puberty in Nelore bulls.

Dehydroepiandrosterone modulates the PTEN/PI3K/AKT signaling pathway to alleviate 4-vinylcyclohexene diepoxide-induced premature ovarian insufficiency in rats.

Dehydroepiandrosterone (DHEA) is frequently integrated as an adjuvant in over a quarter of controlled ovarian hyperstimulation (COH) protocols, despite the ongoing debate regarding its impact. This study aimed to evaluate the efficacy and mechanism of action of DHEA on ovarian follicular development and ovarian response in rats with varying ovarian reserves. The study involved 75 rats categorized into 15 distinct groups. The ovarian tissues of rats in both the normal ovarian reserve group and the premature ovarian insufficiency (POI) group, induced by 4-vinylcyclohexene diepoxide (VCD) injection, were subjected to histomorphological and biochemical analyses following the administration of DHEA, either alone or in combination with COH. Follicle counting was performed on histological sections obtained from various tissues. Serum concentrations of anti-Müllerian hormone (AMH) and the quantification of specific proteins in ovarian tissue, including phosphatase and tensin homolog of chromosome 10 (PTEN), phosphoinositide 3-kinase (PI3K), phosphorylated protein kinase B (pAKT), cyclooxygenase 2 (COX-2), caspase-3, as well as assessments of total antioxidant status and total oxidant status, were conducted employing the ELISA method. The impact of DHEA exhibited variability based on ovarian reserve. In the POI model, DHEA augmented follicular development and ovarian response to the COH protocol by upregulating the PTEN/PI3K/AKT signaling pathway, mitigating apoptosis, inflammation, and oxidative stress, contrary to its effects in the normal ovarian reserve group. In conclusion, it has been determined that DHEA may exert beneficial effects on ovarian stimulation response by enhancing the initiation of primordial follicles and supporting antral follicle populations.

Influence of oral hormonal contraception on the concentration of anti-Müllerian and reproductive hormones in patients with polycystic ovary syndrome

Aim: To investigate the effects of three-month use of oral hormonal contraception (OHC) on hormonal status and ovarian reserve indicator (anti-Müllerian hormone, AMH) in patients with polycystic ovary syndrome (PCOS).Methods: 19 patients with diagnosed PCOS and clinical and laboratory signs of hyperandrogenism without additional comorbidities and co-medication were included in the study. All participants received therapy with the same oral hormonal contraceptive (fixed combination of 0.035 mg ethinyl estradiol and 2 mg cyproterone acetate). The main outcomes were the concentrations of reproductive hormones measured before starting therapy and in the first cycle following therapy. Hormone concentrations were analysed using the immunochemical electrochemiluminescence (ECLIA) method.Results: Initial concentrations of total and free testosterone and AMH were elevated, while initial concentrations of other reproductive hormones were within reference values. By applying the therapy, the concentrations of AMH, luteinizing hormone (LH) and estradiol decreased by more than 20% and those of free testosterone by 85%. The concentration of sex hormone binding globulin (SHBG) increased by 44%.Conclusions: Three months of oral hormonal contraception with 35 μg ethinyl estradiol and 2 mg cyproterone acetate reduced elevated concentrations of AMH and free testosterone in PCOS patients. The decrease in serum AMH concentration indicates a temporary interruption of folliculogenesis as well as the selection of follicles from preantral to antral, and the decrease in androgens has a positive effect on the clinical condition and symptoms of patients with PCOS.

Прогнозирование исходов программ экстракорпорального оплодотворения с использованием модели машинного обучения «Случайный лес»

Currently, in vitro fertilization (IVF) with embryo transfer is the main method of treatment of all forms of infertility, but successful cases ending in pregnancy still account for only a third of all cycles performed. It is necessary to take into account many parameters and investigate the connections between them in order to properly evaluate the results of IVF. Over the past decades, a number of IVF prediction models have been developed with the aim at assessing the outcomes in individual cases, but, given the generally poor prognostic capacity, only a few of them have proven to be clinically significant. This study aimed to create nonlinear IVF outcomes prediction models and identify the most significant factors affecting the said outcomes. Using a database containing information on more than 700 indicators of 7004 women aged 18 to 45 years who participated in the IVF program in Russia from 2010 to 2020, we trained a random forest model that predicted pregnancy in the IVF cycle with ROC-AUC = 0.69. This paper describes 20 most successful predictors of the resulting model and interprets their contribution to the prognosis. Of these, body mass index (BMI) and the number of received and fertilized oocytes have been covered in the scientific literature previously as predictors of IVF outcomes, but other parameters, such as anamnestic data, previous participation in an IVF program (number of cases and their results), as well as serum concentration of AMH, rarely appear in foreign prognostic models.

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.

AMH concentrations in infancy and mid-childhood predict ovarian activity in adolescence: a long-term longitudinal study of healthy girls

AMH concentrations in infancy and mid-childhood predict ovarian activity in adolescence: a long-term longitudinal study of healthy girls

Developmental programming of production and reproduction in dairy cows: II. Association of gestational stage of maternal exposure to heat stress with offspring's birth weight, milk yield, reproductive performance and AMH concentration during the first lactation period

Although the negative effect of maternal exposure to heat stress on production and reproduction of offspring has been reported, there are some discrepancies among various studies about which gestational stage is more critical in this regard. Therefore, the present research was conducted to identify during which stage(s) of pregnancy maternal exposure to heat stress would lead to more dramatic decrease in productive and reproductive performance of offspring. To this end, offspring were classified based on the gestational stage they were in utero exposed to heat stress into four categories, including heat stress exposure (HSE) during only the first trimester of gestation (HSE1), HSE during the first and second trimester of gestation (HSE2), HSE during the second and third trimester of gestation (HSE3) and HSE during only the third trimester of gestation (HSE4). In study I, data of birth weight, milk yield and reproductive variables of 11,788 offspring and data of the month they were conceived were retrieved. In study II, blood samples (n = 521) were collected from offspring in various categories of HSE for measurement of serum AMH. Offspring in HSE1 and HSE2 categories were heavier than offspring in HSE3 and HSE4 categories (P < 0.0001). Offspring in HSE1 and HSE3 categories had the lowest and highest milk production, respectively (P < 0.05). First service conception rate was the greatest and worst in HSE1 and HSE4 categories, respectively (P < 0.05). Service per conception and calving to conception interval were greater in HSE2 than HSE4 category (P < 0.05). Concentration of AMH was lower in HSE1 than HSE4 category (P < 0.05). In conclusion, the present study indicated that the early stage of gestation could be a more critical period for the negative impact of in utero heat stress on developmental programming of milk production and ovarian reserves. Yet an evident temporal pattern for the adverse effect of maternal heat stress on developmental programming of reproductive performance in offspring was not found.

Key features of puberty onset and progression can help distinguish self-limited delayed puberty from congenital hypogonadotrophic hypogonadism.

Delayed puberty (DP) is a frequent concern for adolescents. The most common underlying aetiology is self-limited DP (SLDP). However, this can be difficult to differentiate from the more severe condition congenital hypogonadotrophic hypogonadism (HH), especially on first presentation of an adolescent patient with DP. This study sought to elucidate phenotypic differences between the two diagnoses, in order to optimise patient management and pubertal development. This was a study of a UK DP cohort managed 2015-2023, identified through the NIHR clinical research network. Patients were followed longitudinally until adulthood, with a definite diagnosis made: SLDP if they had spontaneously completed puberty by age 18 years; HH if they had not commenced (complete, cHH), or had commenced but not completed puberty (partial, pHH), by this stage. Phenotypic data pertaining to auxology, Tanner staging, biochemistry, bone age and hormonal treatment at presentation and during puberty were retrospectively analysed. 78 patients were included. 52 (66.7%) patients had SLDP and 26 (33.3%) patients had HH, comprising 17 (65.4%) pHH and 9 (34.6%) cHH patients. Probands were predominantly male (90.4%). Male SLDP patients presented with significantly lower height and weight standard deviation scores than HH patients (height p=0.004, weight p=0.021). 15.4% of SLDP compared to 38.5% of HH patients had classical associated features of HH (micropenis, cryptorchidism, anosmia, etc. p=0.023). 73.1% of patients with SLDP and 43.3% with HH had a family history of DP (p=0.007). Mean first recorded luteinizing hormone (LH) and inhibin B were lower in male patients with HH, particularly in cHH patients, but not discriminatory. There were no significant differences identified in blood concentrations of FSH, testosterone or AMH at presentation, or in bone age delay. Key clinical markers of auxology, associated signs including micropenis, and serum inhibin B may help distinguish between SLDP and HH in patients presenting with pubertal delay, and can be incorporated into clinical assessment to improve diagnostic accuracy for adolescents. However, the distinction between HH, particularly partial HH, and SLDP remains problematic. Further research into an integrated framework or scoring system would be useful in aiding clinician decision-making and optimization of treatment. .

Developmental programming of production and reproduction in dairy cows: I. Association of maternal parity with offspring's birth weight, milk yield, reproductive performance and AMH concentration during the first lactation period

Multiparous dams have been reported to produce offspring with greater fertility and higher AMH concentration, as a marker of ovarian reserves, as compared with nulliparous and primiparous dams. Yet it has remained to be addressed whether this phenomenon can still be true for old multiparous cows which might experience some geriatric changes in their reproductive system. Therefore, the present study was conducted to evaluate the productive and reproductive performance of offspring with different maternal parity. To this end, offspring were classified based on their maternal parities into four categories, including offspring of nulliparous (no previous parity), primiparous (one previous parity), young multiparous (two to six previous parities) and old multiparous (seven or more previous parities) dams. In study I, data of birth weight, milk yield and reproductive variables of 11,788 offspring and data of their maternal parity were retrieved. In study II, blood samples (n = 521) were collected from offspring with various maternal parity for measurement of serum AMH. Birth weight was the lowest in the offspring of nulliparous dams (P < 0.0001) and it was lower in offspring of primiparous and old multiparous dams than offspring of young multiparous dams (P < 0.05). Milk production was the lowest in offspring of old multiparous dams (P < 0.01), and it was lower in offspring of young multiparous dams than offspring of nulliparous and primiparous dams (P < 0.0001). Offspring of old multiparous dams had greater first service conception rate, less services per conception and shorter calving to conception interval than offspring of nulliparous, primiparous and young multiparous dams (P < 0.05). Furthermore, AMH concentration was higher in offspring of old multiparous dams than offspring of nulliparous and primiparous dams (P < 0.05). In conclusion, the present study revealed greater milk production in offspring resulting from dams with lower parity, probably due to the genetic selection for improvement of milk production in dairy cows which imparts the younger generations greater genetic merits for milk production. Reproductive performance, however, was greater in offspring born to dams with higher parity, particularly those born to old multiparous dams, and this phenomenon might be related to their lower milk production and higher AMH concentration.

P-443 Resumption of ovulation during lifestyle intervention in anovulatory women with PCOS and obesity is associated with reduction of serum AMH and androgens concentrations

Abstract Study question Are there differences in AMH and androgens concentrations between women with PCOS who resume ovulation (RO+) and those remain anovulatory (RO-) during lifestyle intervention? Summary answer RO+ women showed significant decrease in AMH and 11β-hydroxyandrostenedione concentrations at three months, and increase in SHBG concentrations at six months compared to RO- women. What is known already Lifestyle interventions have been shown to reduce clinical and biochemical hyperandrogenism in women with PCOS. Weight loss of 5-10% may reverse anovulatory status, thereby increasing natural conception rates. However, the underlying mechanisms why some women with PCOS remain anovulatory and others resume ovulation after weight loss are unclear. Reproductive characteristics at baseline and a greater degree of change in endocrine and metabolic features with lifestyle intervention may be crucial for ovulatory response. Study design, size, duration We used data and samples originating from an RCT which examined the efficacy of a six-month lifestyle intervention prior infertility treatment compared to prompt infertility treatment on live birth rate in women with obesity. In total of 577 women with obesity were randomized between 2009 and 2012. Anovulatory women with PCOS who were allocated to the intervention arm of the original RCT (n = 97) were included in the current analysis. Participants/materials, setting, methods We defined women as ovulatory during or after intervention based on the following criteria either: (1) spontaneous pregnancy; Or (2) Treatment strategy after lifestyle intervention; expectant management; (3) or IUI treatment in natural cycles. The steroid hormones were measured using LC-MS/MS. Multilevel analysis with the adjustment of baseline measurements was used to examine differences in changes in AMH and androgens concentrations between RO + (n=34) and RO- groups (n = 61) at three and six months after intervention. Main results and the role of chance At baseline, the mean age was 27.5 ± 3.6 in RO+ group and 27.9 ± 4.1 years in RO- group (p = 0.65). The mean weight was 101.2 ± 9.5 and 105.0 ± 14.6 kg, respectively (p = 0.13). AMH concentrations showed significant differences between RO+ women and RO- women (median and IQR 4.7 [3.2; 8.3] in the RO+ group and 7.2 [5.3; 10.8] ng/mL in the RO- group, p = 0.03). Androgen concentrations did not differ between the two groups. During and after lifestyle intervention, RO+ women had significant decrease in AMH (mean difference: –1.6 ng/mL, 95%CI: –3.0 to –0.20, p = 0.03) and 11β-hydroxyandrostenedione (mean difference: –1.7 nmol/L, 95%CI: –3.1 to –0.41, p = 0.01) concentrations than RO- women at three months. SHBG concentrations were significantly increased in RO+ compared to RO- women at six months (mean difference: 11 nmol/L, 95%CI: 1.1 to 22, p = 0.03). Changes in 11-ketotestosterone (three months mean difference: –0.15 nmol/L, 95%CI: –0.49 to 0.20, p = 0.41; six months: –0.39 nmol/L, 95%CI: –1.3 to 0.57, p = 0.43) and testosterone (three months mean difference: 0.13 nmol/L, 95%CI: –0.32 to 0.57, p = 0.58; six months: –0.29 nmol/L, 95%CI: –0.81 to 0.23, p = 0.27) did not differ at three or six months between groups. Limitations, reasons for caution The indirect parameters to confirm ovulatory cycles at the end of lifestyle program and small sample size may limit the robustness of the results. Wider implications of the findings Reduction of serum AMH and androgen concentrations during lifestyle intervention is associated with recovery of ovulatory cycles. When our results are confirmed in other studies, serum AMH and androgens concentrations could be monitored during lifestyle intervention to provide individualized recommendations on resumption of ovulatory cycles in anovulatory women with PCOS. Trial registration number NTR1530

P-298 Women undergoing IVF-ICSI cycles after mild Covid-19 infection do not show a poor ovarian response: A prospective randomized controlled study

Abstract Study question Does mild COVID-19 infection in women undergoing IVF-ICSI cycles affect their ovarian reserve ? Summary answer A recent past mild COVID-19 infection does not seem to alter the ovarian reserve testing and ovarian response to stimulation in women undergoing IVF-ICSI cycles. What is known already Since December 2019, the world has been facing a COVID-19 pandemic. Besides its effect on mortality, COVID-19 infection raises questions about short and longterm effects on general health. Clinical manifestations are highly heterogeneous and involve many different organs. The SARS-CoV-2 virus penetrates human cells by directly binding with angiotensin-converting enzyme 2 (ACE2) receptors present on the cell surface.The ACE2 receptors are present in testes and in ovarian tissue. In the ovary, ACE2 plays a role in the response to gonadotrophins, steroidogenesis regulation, and in follicle development, angiogenesis and degeneration and therefore, SARS-CoV-2 could be responsible for adversely affecting ovarian reserve. Study design, size, duration A prospective randomized controlled study was conducted between June 2020 and December 2021. Women with primary or secondary infertility undergoing IVF-ICSI between the age of 25-40 years were included. All the women underwent a COVID testing by RT-PCR and were subsequently tested for ovrian reserve by assessing their AMH and AFC (USG). Participants/materials, setting, methods The study population consisted of 128 women, 22% of whom were COVID RT-PCR positive. None of the tested women presented with a history of severe COVID-19 infection. They were randomized into two groups depending on whether they were positive for past COVID-19 infection or negative. These women were then subjected to AMH testing and estimation of AFC by transvaginal ultrasonography. Main results and the role of chance The difference between the initial AMH concentration and AMH concentration tested during ART treatment was not significantly different between the COVID RDT positive group and COVID RDT negative group (–1.24 ng/ml [–0.35 to –1.61) versus –0.56ng/ml [–0.15 to –1.11], P = 0.22). Similarly the AFC (Antral Follicle Count) was also not significantly different between the two groups of patients. The results of this prospective study showed that, based on AMH concentrations, mild COVID-19 infection did not affect ovarian reserve in our population of asymptomatic women who underwent an ART protocol susequently. Limitations, reasons for caution First, it has been shown that the AMH concentration is modified during ART treatment as this hormone is secreted by granulosa cells of small growing follicles thus reflecting the granulosa cell activity. Second, a relatively small number of women were included in the analysis and larger study groups are required. Wider implications of the findings The wider implication of our study is that AMH concentrations were tested in the same women at different time points and could, therefore, analyse any potential modification of the ovarian reserve after COVID-19 infection. This information can be used to reassure the population who have been afflicted by COVID-19 infection. Trial registration number not applicable