Effect of autologous platelet rich plasma on anti-mullerian hormone and antral follicle count in sub fertile women with poor ovarian reserve

Background: Ovarian aging may be reversible. Platelet rich plasma (PRP) has growth factors that promote cellular proliferation and folliculogenesis. Recently published studies and case reports suggest that ovarian rejuvenation can be done by PRP treatment. The objective of the study was to evaluate the effect of platelet rich plasma on ovarian reserve markers such as anti mullerian hormone (AMH) and antral follicle count (AFC) in sub fertile women with poor ovarian reserve (POR).Methods: The self-controlled quasi experimental study was carried out on 29 sub fertile women with poor ovarian reserve. They were selected for laparoscopic tubo-peritoneal evaluation as they could not afford in vitro fertilization. During laparoscopy, 5 ml of pre prepared autologous PRP was injected into each ovary. Post-PRP AMH and AFC were measured at every cycle for a period of at least three (3) months and compared with base line values.Results: Mean age of participants was 35.9±3.2 years. Baseline AMH was 0.31±0.17 ng/ml and baseline AFC was 3.41±0.73. AMH was raised on first, second and third cycle from base line values in 58.62%, 86.21% and 91.30% of the study population respectively. AMH changes in all three cycle were statistically significant. Pregnancy occurred in three (10.34%) women during the study period.Conclusions: The injection of autologous PRP into human ovaries is a safe procedure to improve ovarian reserve markers (AMH and AFC) in women with POR.

Role of AMH in Prediction of Menopause

Anti-Müllerian Hormone (AMH) is produced by small antral follicles and has evolved over the past three decades as an assumed potential marker of the number of follicles in the human ovaries, also known as ovarian reserve. This quantitative measure, given the gradual decline over time and its non-replenishable feature, could be the dreamed marker for predicting the final exhaustion of ovarian storage: the post-menopause. This introductory chapter summarizes current knowledge with regard to the contribution of serum AMH measurements to predict age of normal menopause and critically discuss its potential in this regard. Furthermore, its predictive role in the context of menopause in association with several frequently occurring fertility disorders such as premature menopause, polycystic ovarian syndrome and endometriosis are discussed. Overall, while ovarian reserve markers including AMH are unmistakably related to age at menopause, they are insufficiently precise to inform on an individual’s journey of ovarian aging.

P–640 High physical activity and ovarian reserve: A prospective study of normo-ovulatory professional athletes

Study question Is high physical activity (HPA) associated with low ovarian reserve in normo-ovulatory, reproductive-age women? Summary answer HPA does not affect ovarian reserve negatively. What is known already HPA is associated with menstrual irregularities and subsequent potential infertility, probably through hypothalamic neuroendocrine pathways. However, it is not yet known whether HPA influences the ovarian reserves of normo-ovulatory, reproductive-age women. Study design, size, duration This observational, cross-sectional study compared 30 professional female athletes who were engaged in HPA for at least 3 years prior to study recruitment, with high International Physical Activity Questionnaire (IPAQ) scores and 30 women who did not engage in physical activity. The study was conducted at a tertiary medical center from 2017–2020. Participants/materials, setting, methods Physically active, normo-ovulatory women (n = 30), ages 20–35 years were recruited from The Wingate Institute, the Israeli National Institute for Sport Excellence. Non-physically active women (n = 30), matched by age and BMI to the HPA group, were recruited from the hospital staff. Both groups were evaluated for ovarian reserve markers on day 2–5 of the menstrual cycle, including follicular stimulating hormone (FSH), antral follicle count (AFC), anti-Mullerian hormone (AMH) and Inhibin B. Main results and the role of chance The average age of the athletes (HPA group) was 30.1±2.1 years and of the nonactive (control) group 31.6±3.8 years (p = 0.071). BMI of the 2 groups was similar (22.6±2.4 vs. 21.3±2.6; p = 0.075) for the HPA and control groups, respectively. Regarding ovarian reserve, no significant differences were observed between the HPA group and the control group with respect to FSH (p = 0.304), AFC (p = 0.27), AMH (0.507) or Inhibin B (p = 0.074). For the HPA group, older age at menarche was positively associated with AFC (p = 0.008) and AMH (p = 0.009) and not with FSH levels (p = 0.313). For the nonactive group, no significant association between age at menarche and FSH levels, AFC or AMH was found (p = 0.433, p = 0.274 and p = 0.163, respectively). Additionally, for the HPA group, duration of physical activity per week (hours) was not significantly associated with FSH levels, AFC or AMH (p = 0.619, p = 0.608 or p = 0.997, respectively). Limitations, reasons for caution Although we investigated the ovarian reserves of 30 women engaged in HPA, a larger cohort would provide more information. Information on diet and sleep habits was not evaluated and may result in some confounding. Moreover, it would be more informative if we also followed these women regarding fecundability and fertility. Wider implications of the findings: This study demonstrated that HPA may not negatively affect ovarian reserve markers. These findings may provide reassurance for women who are engaged in HPA and attempting pregnancy. Further research needs s to be confuted. Trial registration number 0247–16

O-117 Prevalence of Fragile X Mental Retardation 1 premutation (FMR1) in young infertile women with diminished ovarian reserve. Implications in clinical practice

Study question Are young infertile patients with diminished ovarian reserve (DOR) elegible to perform the FMR1 premutation study? Summary answer Study of the FMR1 premutation should be considered in infertile young patients with DOR in order to give them an adequate genetic counselling. What is known already FMR1 gene may have some reproductive implications. Most notable is that FMR1 premutation expansions are associated with premature ovarian insufficiency (POI), diagnosed by amenorrhea or oligomenorrhea and FSH hormonal levels >25U/L before 40 years old. Presence of FMR1 premutation implies a risk of develop POI up to 24% and having an offspring with fragile X syndrome. The frequency of FMR1 premutation in general population is estimated in 0.3-0.7%. The role of FMR1 premutation expansions in diminished ovarian reserve (DOR) patients is not clearly established and could be considered as a previous step to POI that may be related to sterility. Study design, size, duration Retrospective review of the FMR1 gene study requested in patients of an Assisted Reproduction Unit of a tertiary Hospital in Barcelone from January-2016 to December-2019. A total of 307 cases were evaluated to determine the number of CGG repeat and AGG interruptions to assess the FMR1 gene status. Participants/materials, setting, methods A total of 307 samples were assessed. Clinical and reproductive data were collected. The FMR1 status was requested on patients who present: a) POI (n = 60); b) Family history of the FMR1 mutation (n = 11); c) Infertile normo-ovulatory and young (≤35 years old) women with DOR defined as antral follicle count (AFC) < 7 and antimüllerian hormone <0.8ng/ml (n = 71); d) Miscellaneous (n = 29) FMR1 was studied in 136 oocyte donors (screened by protocol), this was considered control group. Main results and the role of chance Mean age (±SD) of infertile DOR group was 32.7 +/- 2.1 years old (range 26-35) and showed altered ovarian reserve markers: AMH 0.43 ng/ml (SD ± 0.28) and AFC 4.27 (SD ± 2.1) follicles. In this group, 4 FMR1 premutation cases were found. Mean age (±SD) in control group was 26.28 +/- 5.2 years old and presented normal AMH and AFC values. One FRM1 premutation carrier was detected among 136 patients, prevalence comparable to the non-sterile population. The prevalence of FRM1 premutation was significantly higher in the DOR infertile group 5,6% vs 0,73% in the donors’ group (p = 0.02). Significant differences were observed also in terms of age and ovarian reserve markers between both groups. Very few cases of POI patients or family history of Fragile X Syndrome have been evaluated, due to the fact we are not a reference of these kind of patients. Among patients with a family history, 1 case from 11 (9.1%) was detected. In the POI group, three cases of premutation out of 60 (5%) were found. Limitations, reasons for caution This is a retrospective study with limited determinations of FMR1 studies. Donor screening and young infertile patients with significant low ovarian reserve are the main indications to request FMR1 status gene, so may lead to a selection bias. Wider implications of the findings These results should be confirmed prospectively in a higher population of infertile young patients with DOR, in order to identify the profile of infertile patient with diminished ovarian reserve who are elegible to perfom FMR1 gene premutation to give them an adequate clinical and genetic counselling. Trial registration number not apllicable

Ovarian Reserve Markers in Premature Ovarian Insufficiency: Within Different Clinical Stages and Different Etiologies

ObjectiveTo characterize the ovarian reserve indicators for premature ovarian insufficiency (POI) at different disease stages and with various etiologies.MethodsAccording to different FSH levels and menstrual conditions, patients with normal ovarian reserve (NOR with 5 IU/L<FSH<10 IU/L, n=987), precursor stage of POI (pre-POI with 10 IU/L<FSH ≤ 25 IU/L, n=410), early POI (25 IU/L<FSH ≤ 40 IU/L n=147), and premature ovarian failure (POF with FSH>40 IU/L, n=454) were retrospectively screened and their records were abstracted from Reproductive Hospital Affiliated to Shandong University between 2014 and 2019. Based on the known etiologies, POI patients were subdivided into genetic, iatrogenic, autoimmune and idiopathic subsets according to the known etiologies. The phenotypic features were compared within different subgroups, and the predictive value of ovarian reserve markers was analyzed.ResultsThe ovarian reserve indicators consecutively deteriorated with the progress of ovarian insufficiency, indicated as an increase of FSH and LH but decrease of AMH, inhibin B, AFC, E2 and T (P<0.01). Most of them changed significantly from NOR to pre-POI while remained relatively stable at a low level or even undetectable at early POI and POF stage. AMH showed the highest predictive value for pre-POI (AUC 0.932, 95% CI 0.918-0.945) and POI (AUC 0.944, 95% CI 0.933-0.954), and the combination of AMH and AFC was highly promising for early prediction. Additionally, significant differences existed in AMH, inhibin B and AFC among women with different etiologies of POI (P<0.05), and the genetic POI presented the worst hormone status.ConclusionsOur study indicated a high heterogeneity of POI in both endocrine hormones and etiological phenotypes. The quantitative changes and cutoff values of AMH and AFC could provide new insights in the prediction and early diagnosis of POI.

Body Mass Index (BMI) dependent effect of thyroid stimulating hormone (TSH) and gonadotropins on ovarian reserve markers in the secondary infertile women at fertile age.

Background: Infertility is a medical condition when a couple fails to conceive after having regular unprotected intercourse without the use of any contraceptive, it a complex global health issue that can be primary with no previous conception or secondary with one or more previous conceptions. A number of anomalies in the reproductive track govern the state of infertility in female of reproductive age.Materials and Methods: The study was conducted on 100 secondary infertile women based on BMI groups {Normal 18-23.9 kg/m2 (N=35) and Overweight 24-27 kg/m2 (N=65)}, attending tertiary care infertility center: Lahore Institute of Fertility and Endocrinology, Hameed Latif Hospital. The present analytical cross sectional study was conducted to assess the BMI based combinatorial effect of gonadotropins with thyrotropin and ovarian reserve markers in secondary infertile women. Serum hormonal levels of TSH, LH, FSH and AMH were measured by using Roche electrochemiluminescence immunoassay (ECLIA) and AFC was recorded by transvaginal ultrasonography. The results were statistically analyzed by Spearman correlation test using XLSTAT, considered significant at p-value <0.05. Results: A total of 18% of secondary infertile women with normal BMI were found to have a lower serum TSH levels (<0.27µIU/ml) which can be characterized as hyperthyroidism as compared to overweight population. A strong significant positive correlation was found in the TSH, age and BMI, however, these factors were found to be negatively correlated with AMH and AFC. Gonadotropins level was increased with increase in TSH levels among participants with normal BMI but decreased with TSH escalation values among overweight population. Conclusion: TSH was found to be one of the most important diagnostic factors of infertility must be monitored in relation with other parameters (AMH, AFC, FSH, and LH) in order to spot instigation point, as it directly acts upon ovulation surge by controlling gonadotropins related actions on ovarian reserve. Weight should also be assessed regularly with age to minimize the infertility issues.

ADA activity in the follicular fluid of infertile women with diminished ovarian reserve can act as a predictor of ovarian reserve

Background: Adenosine deaminase (ADA) catalyses the deamination of adenosine to inosine. In the human reproductive tract, the importance of enzymes that affect metabolism of adenosine, particularly ADA, has been emphasized. It is aimed to evaluate the plasma and follicular fluid (FF) activities of total ADA (ADAT) in infertile women and to determine its relation with ovarian reserve markers and in vitro fertilization (IVF) outcomes.Methods: Plasma and FF activities of ADAT were measured in 106 infertile women. Its relation with ovarian reserve markers and IVF outcomes were determined.Results: There was a significant difference in the ADAT activities between plasma and FF of infertile women (p<0.01). The activity of plasma ADAT was higher than FF ADAT in infertile women (p<0.01). The activity of FF ADAT in DOR group was higher than that of the others (p<0.01). In DOR group; the activity of FF ADAT activity had a negative correlation with BMI and a positive correlation with FSH and no relation with IVF outcomes.Conclusions: Increased ADAT activity can lead to reduced adenosine levels, which might be resulted in disturbed fertility process. The activity of FF ADAT activity might be important for fertility work-up. Further studies are needed.

Female adolescents and young women previously treated for pediatric malignancies: assessment of ovarian reserve and gonadotoxicity risk stratification for early identification of patients at increased infertility risk

BackgroundChildhood and adolescent cancer survivors (CACSs) are at risk of adverse reproductive outcomes. Assessment of follicle-stimulating hormone (FSH) levels is the most common test used to diagnose premature ovarian insufficiency (POI) whereas anti-m|llerian hormone (AMH) and antral follicle count (AFC) have been proposed as ovarian reserve markers. We assessed the correlation between these markers and treatment gonadotoxicity risk (GR) in CACSs.Subject and methodsA total of 55 female CACSs were enrolled. GR was graded as low, medium, or high according to classifications based on disease and treatments and on cyclophosphamide equivalent dose score. FSH, AMH, and AFC were determined. POI was defined by amenorrhea and FSH>30 IU/L. For remaining patients, diminished ovarian reserve (DOR) was defined by AMH<5th centile. FSH and AFC cut-offs proposed in the literature as DOR markers were also considered (FSH>10 IU/L or >95th centile; AFC<8 or <5th centile).ResultsOvarian reserve results to be compromised in 23 (41.8%) patients: 14 with DOR and 9 with an established POI. Results showed GR classifications to be a good predictor of ovarian reserve, with significantly lower AMH and AFC in the high-risk groups. AFC resulted to be directly correlated with AMH (r=0.75, p<0.001).ConclusionsIn CACSs, GR classifications correlate with post-treatment AMH and AFC. These are useful tools in the early identification of young patients with DOR, who may benefit from reproductive and fertility preservation counseling. Further studies are needed to determine the rate and time of progression from DOR to POI in this population.