Ovarian Reserve Tests Research Articles

P–303 Similar long term recurrence rates with cystectomy and CO2-laser vaporization for endometrioma: a retrospective study

Abstract Study question Is there a difference in recurrence rate of endometrioma(s) after cystectomy versus CO2-laser vaporization of the cyst wall? Summary answer Similar rates of imaging based recurrence or need for reintervention for endometrioma were observed after cystectomy versus CO2-laser vaporization. What is known already Surgical treatment of endometrioma(s) is mainly performed by 2 types of procedures: cystectomy and ablation. When performing surgery for endometrioma(s), a balance should be made between minimal destruction of normal ovarian cortex and maximal completeness to avoid (early) recurrence. Previous studies have shown that cyst recurrence rates were higher with ablation using bipolar current than after cystectomy. However, only 2 groups have evaluated recurrence rates after cystectomy versus CO2 laser vaporization and found no difference with extended follow-up. Furthermore, ablation with CO2 laser may be less invasive than conventional cystectomy with increased preservation of antral follicles in favor of ablation. Study design, size, duration Single-center retrospective study on data of 271 patients operated between January 2010 and December 2014. Participants/materials, setting, methods Women of reproductive age (18–45 years), undergoing CO2 laser laparoscopic excision of any rAFS-stage endometriosis with at least one endometrioma, were eligible for the study. All 271 included patients were treated in a tertiary referral center for endometriosis of a University Hospital, and underwent complete CO2-laser laparoscopic surgery for endometrioma(s). 155 underwent cystectomy, 77 CO2 laser vaporization, and 46 a mixed technique. Main results and the role of chance The mean duration of follow-up was 58 months. Primary outcome studied was the comparison of recurrence rates between cystectomy and vaporization; secondary outcomes included pregnancy rate and ovarian reserve testing. Recurrence was defined as either imaging based (i.e. cyst recurrence identified at ultrasound and/or MRI) or need for reintervention for suspected cyst recurrence. Imaging based recurrence was reported in 9.92% of patients (n = 12/121) treated with cystectomy and in 11.76% of patients (n = 6/51) who underwent a CO2 laser vaporization (p = .62). The need for reintervention for endometrioma(s) was also similar in both groups, with a rate of 3.23% (n = 5/155) after cystectomy and 4.29% (n = 3/70) after CO2 laser vaporization (p = .567). No difference was seen regarding AMH drop pre- versus postoperatively (p=.233). The 2 study groups were similar, except for the mean cyst diameter, which was higher in the cystectomy group (42.36 ± 25.49 mm) compared to the CO2 laser vaporization group (31.7 ± 26.98 mm) (p = <.001). This suggests that smaller endometriomas might be more likely to undergo CO2 laser vaporization. Limitations, reasons for caution The retrospective character of the study may induce information bias concerning the registration of recurrence. Moreover, regarding the evaluation of imaging-based recurrence, a selection bias cannot be excluded, because most likely only patients complaining about pain would be referred for an ultrasound or planned for a reintervention. Wider implications of the findings: In this study, similar rates of recurrence for endometrioma(s) were observed after cystectomy versus CO2-laser vaporization. Since previous studies suggested that CO2-laser vaporization may cause less damage to the adjacent ovarian tissue, we consider this a valuable alternative technique, especially for women with a future child wish. Trial registration number S59032

P–749 Knowledge of women undergoing surgery for endometrioma regarding the impact of the disease and its treatment on ovarian reserve and fertility

Abstract Study question Do women undergoing surgery for endometrioma due to pain, a cyst and/or subfertility understand the impact of the disease and its treatment on ovarian reserve and fertility. Summary answer The majority of women treated in a fertility setting are well informed compared to those in a general medical setting. What is known already: Infertility affects 30% to 50% of women with endometriosis. Ovarian endometriomas are reported in 17–44% of infertile women with endometriosis and are typically associated with more severe disease. Endometriomas are associated with diminished ovarian reserve, due to the endometrioma per se or due to surgical interventions required to treat and excise the disease. ESHRE guidelines recommend that women should be informed pre-operatively of the potential reduction in ovarian reserve associated with surgery and that ovarian reserve tests should be performed when future fertility is a concern. Study design, size, duration In conjunction with our histopathology colleagues we identified a cohort of women with a histological diagnosis of one or more ovarian endometriomas who underwent surgery in our unit between 2010 and 2019. We developed a scoping questionnaire, targeted at women currently over the age of 40, who had previously undergone surgery for endometrioma under the age of 35. Patients were contacted by telephone and consent obtained to send an email with a survey link. Participants/materials, setting, methods We identified 47 women who had a histological diagnosis of endometrioma. Of these, 30 were contactable by telephone, of whom 29 consented to being sent information regarding the study and a link to the questionnaire. 21 women completed the survey. Respondents were divided into 2 groups for analysis. Group 1 cited ‘fertility’ or ‘both pain and fertility’ as an indication for their surgery while group 2 had ‘pain’ or ‘ovarian cysts’ but no fertility concerns. Main results and the role of chance: The majority (62%) of patients were diagnosed with endometriosis while aged 25–34. The indication for surgery was evenly divided between pain (32%), fertility (37%) and ovarian cysts (37%). 60% of women reported having endometriomas diagnosed preoperatively. Striking differences were noted between groups 1 and 2. Of the women who cited ‘fertility’ or ‘both pain and fertility’ (n = 9) as an indication for their surgery, 78% (n = 7) reported being aware of any possible negative impact of endometriosis on their fertility, with 78% also being aware of the possible negative impact of surgery for endometriosis on their fertility. This compared to only 36% (n = 4) and 27% (n = 3) respectively in Group 2. In group 1, 56% (n = 5) remembered having an AMH level checked pre operatively while 78% (n = 7) also had an ultrasound pre-operatively. In contrast, only 33% (n = 3) of Group 2 remember having an AMH level checked pre operatively though 64% (n = 7) had an ultrasound pre-operatively. Of those whose surgery was performed by a fertility specialist, 75% (n = 6) reported being aware of the impact of endometriosis and also the impact of surgery on ovarian reserve, compared to 44% (n = 4) of those who surgery was performed by a non-fertility specialist. Limitations, reasons for caution This is a retrospective study and the numbers are small. We were only able to identify women with an endometrioma via pathology records, so those with no excision of disease (eg those who had ablation of an endometrioma) were excluded from this analysis. Wider implications of the findings: This suggests the majority of patients treated in a fertility setting are counselled regarding the benefit of surgery but also the risk to ovarian reserve. This is not the case in other settings. It is time to disseminate guidelines such as those produced by ESHRE to our general gynaecology colleagues. Trial registration number Not applicable

O-114 Improved safety and efficiency of individualised versus conventional gonadotropin dosing for ovarian stimulation in IVF/ICSI: an individual patient meta-analysis (IPD-MA)

Abstract Study question Does an individualised, weight- and AMH-based dosing approach with follitropin delta improve live birth rate, safety, and efficiency, compared to conventional dosing in IVF/ICSI? Summary answer Individualised ovarian stimulation performs similarly for live birth rate (increased in normal-high AMH), and reduces the incidence of OHSS and total FSH dosage. What is known already Previous studies investigated the effect of individualized gonadotropin dosing in IVF/ICSI using ovarian reserve tests such as anti-Müllerian hormone (AMH) and antral follicle count (AFC). A Cochrane Review concluded that individualised dosing in IVF is associated with a reduction of ovarian hyperstimulation syndrome (OHSS), but no effect on live birth rate. It is hypothesized that an individualised dosing approach is predominantly beneficial in the patients who are potentially normal or high responders. This study addresses the performance of a new human recombinant FSH (follitropin delta) with individualised dosing based on AMH and body weight. Study design, size, duration This is an individual participant data meta-analysis (IPD-MA) of three follitropin delta phase 3 trials, executed in Europe and North- and South America, South-East Asia, and Japan. All trials were randomized, controlled, assessor-blinded, multicenter studies in which individualised follitropin delta vs. conventional follitropin alpha or beta were compared. Women were followed from inclusion, at start of their first fresh IVF/ICSI cycle, until 4 weeks after live birth. Participants/materials, setting, methods Women aged 20-40 yrs, undergoing their first IVF/ICSI cycle, were randomly assigned to follitropin delta (AMH < 15 pmol/L: 12 µg/day; AMH ≥ 15 pmol/L: 0.10-0.19 µg/kg/day: maximum 12 µg/day) or conventional follitropin alpha or beta (150 IU/day for 5 days, possible subsequent dose adjustments). The IPD-MA was performed using logistic regression analysis. Planned subgroup analyses were performed for expected normal/high responders (serum AMH ≥15 pmol/L), and expected low responders (serum AMH <15 pmol/L). Main results and the role of chance Nearly 2,700 women were randomised and exposed: n = 1,348 for conventional dosing regimen with follitropin alpha or beta, and n = 1,334 for individualised dosing with follitropin delta. Live birth rate was similar for both groups (29.5% in follitropin delta vs. 26.9% in follitropin alpha/beta; OR 1.14 (0.96-1.35)). However, in expected normal to high responders live birth rate was significantly increased for those receiving individualised follitropin delta (31.4% vs. 25.9%; OR 1.31 (1.06 - 1.62)). Mean number of transferred embryos/blastocysts was comparable (0.95 vs. 0.94, respectively; mean difference 0.0076; NS), and did not differ when subgroup analyses were performed for normal/high AMH and low AMH. The occurrence of early OHSS was significantly reduced in individualised follitropin delta (4.0% vs. 6.4%; OR 0.62 (95% CI 0.43-0.88)), in subgroup analyses a similar reduction was identified. Total dosage of FSH was significantly lower in individualized follitropin delta (84.5 vs. 112.1 µg; mean difference -27.5 µg (95% CI -30.0 - -25.1)), with a more pronounced effect in normal to high AMH (mean difference -36.5 µg (95% CI -39.2 - -33.7)). Gestational age and birth weight were similar. The IPD-MA identified similar findings among women from the three studies with their different ethnic backgrounds. Limitations, reasons for caution For individualised dosing with follitropin delta, it was observed that the number of cryopreserved embryos was significantly lower (2.4 vs. 3.0, mean difference -0.67 (p < 0.05)), and it remains unclear whether this affects cumulative live birth rate. Wider implications of the findings Individualised dosing with gonadotropin delta is similarly successful in terms of live birth (increased for normal-high AMH women), reduces safety risks, and is more effective with regard to gonadotropin dosage, compared with conventional dosing in IVF/ICSI. Treatment costs are reduced by prescription of lower gonadotropin doses and OHSS reduction. Trial registration number NCT01956110, NCT03228680, NCT03296527

P–695 Establishing predictors of the mode of conception in fertility patients presenting with a clinical pregnancy

Abstract Study question What are the predictors for pregnancies conceived spontaneously (SC), by ovulation induction+/-insemination (OI±IUI) or via In-Vitro Fertilization(IVF), and what proportion of pregnancies were conceived with each method? Summary answer Pregnancies were conceived by SC(27.7%), OI±IUI(33%) or IVF(39.2%).Unexplained infertility positively-predicted SC and OI±IUI-conceptions. Male factor-infertility demonstrated the opposite trend, positively predicting IVF. Endometriosis negatively-predicted SC. What is known already Spontaneous conception (SC) occurs regularly among infertility patients. Most studies have evaluated predictors of pregnancy among women with infertility who were trying to conceive. Few studies have addressed the role of different factors on the mode of conception in infertility patients who were pregnant. Factors found in some studies to be related with a SC were younger female age, shorter duration of infertility, fewer failed IVF cycles, and diagnosis of unexplained-infertility. Study design, size, duration We conducted a retrospective cohort study at a University fertility-center over a six-month period in 2019 and 2020. We reviewed viability scans of 285-patients. Mode of conception was recorded as Spontaneous, OI±IUI, or IVF. Patients’ demographics, obstetric and fertility diagnosis as well as base-line hormones and ovarian reserve testing were extracted to calculate predictors for the mode of conception. Pregnancy was defined as an intra-uterine fetal sac on a transvaginal ultrasound in the 1st-trimester. Participants/materials, setting, methods Parametric analysis was done using ANOVA and Tukey’s post-hoc test. Nonparametric analysis was performed using the chi-square test. Predictors of the mode of conception were calculated by multivariate regression analysis using the variables not in the equation model including the following parameters: male and female age, gravidity, parity, ectopic-pregnancies, infertility diagnosis, baseline serum: FSH, estradiol, TSH, AMH, and AFC. Data is presented as mean ±SD or percentage. P < 0.05 was significant. IRB approval was obtained. Main results and the role of chance 79 (27.7%) of pregnancies were SC, 94 (33%) resulted from OI±IUI, and 112 (39.2%) from IVF. Demographics didn’t differ between the groups including: female age(p = 0.06), male age(p = 0.79), gravidity (p = 0.47), parity(p = 0.7), ectopic-pregnancies(p = 0.07), baseline serum FSH(p = 0.29), estradiol(p = 0.65), TSH(p = 0.56), AMH(p = 0.42), and AFC(p = 0.06). Infertility diagnoses differed when comparing SC, OI±IUI and IVF conceptions respectively: Unexplained (22.7%, 22.3%, 15.1%, p = 0.03), Male-Factor(MF) (25%, 27.6%, 42.8%, p = 0.042), Tubal-factor (2.5%, 2.1%, 13.4, p = 0.002) and Ovulation-disorders/PCOS (24%, 32%, 12.5% p = 0.002). Endometriosis trended higher in women with IVF (p = 0.09). A positive predictor for SC was unexplained infertility(p = 0.0001). A negative predictor was endometriosis(p = 0.005). SC was sub-significantly less likely in the presence of MF (p = 0.057). Unexplained-infertility was a positive predictor for OI±IUI pregnancies(p = 0.047), whereas MF was a negative predictor(p = 0.0001). As for IVF-conceptions, MF was a positive predictor(p = 0.008), while unexplained-infertility negatively predicted conception by IVF(p = 0.018). Ovulation-disorders/PCOS trended lower in women with IVF (p = 0.052). While baseline serum estradiol levels were similar between groups (means 194–218pmol/L), multivariate regression showed it to be a predictor for OI±IUI and IVF conceptions. The clinical significance of this finding is not clear. Interestingly, female age and ovarian reserve were not found to predict one type of conception over another. Other possible predictors in the model were not significant. Limitations, reasons for caution This retrospective cohort may hide underlying bias. Clinical pregnancies were evaluated and not live birth. Our cohort represents patients that conceived and do not offer information about the entire sub-fertile population that is treated in our center, which is also a strength as it’s a novel way of evaluating predictors. Wider implications of the findings: Among patients that conceived spontaneously, advanced age and ovarian reserve did not play a negative role. Predictors of pregnancy were confirmed as expected with the majority of unexplained infertility conceptions occurring spontaneously or with OI+/-IUI, patients with Male factor infertility often conceived by IVF, and ovulation disorders by OI+/-IUI. Trial registration number NA

O-174 Individualized versus standard FSH dosing in predicted poor responders: an RCT

Abstract Study question Is there a difference in fertility outcomes between individualized or standard FSH dosing in women scheduled for IVF with an expected poor response? Summary answer In predicted poor responders (AFC<10) undergoing IVF/ICSI, individualized FSH dosing does not improve ongoing pregnancy rates as compared to a standard FSH dose. What is known already Poor responders usually lead to many detrimental effects on IVF outcomes due to low oocyte number and quality which in turn result in low pregnancy outcomes and an increased chance of cycle cancellation. Clinicians often individualize the FSH dose using ovarian reserve tests (ORT), including antral follicle count (AFC), basal FSH (bFSH), and anti-Mullerian hormone (AMH). However, it is unclear whether individualized FSH dosing improves clinical outcomes. Study design, size, duration Between March 2019 and April 2020, we performed a single-center, parallel, open-label RCT in women with an AFC<10. A total of 661 women were randomized either to start FSH dosing at 300IU/225IU or 150IU. The primary outcome was live birth attributable to the first ART cycle within 18 months of randomization. In this abstract, we report ongoing pregnancy rates. Live birth date will be available at the meeting. Participants/materials, setting, methods Women referred for their first IVF/ICSI cycle, <43 years of age, AFC<10 were approached. A total of 328 women were allocated to the individualized group and 333 women were allocated to the standard group. In the individualized group, women with AFC 1-6 were assigned to 300IU/day (n = 122), while women with AFC 7-9 were assigned to 225IU/day (n = 206). In the standard group, women were assigned 150IU/day. Outcomes were evaluated from an intention-to-treat perspective. Main results and the role of chance For ongoing pregnancy rate attributable to the first ART cycle for individualized versus standard dosing was comparable [52.44% vs 46.25%, relative risk (RR): 1.29 (95%CI, 0.94-1.74), P = 0.11]. Biochemical pregnancy rate [62.50% vs 62.16%, RR: 1.01 (95%CI, 0.74-1.39), P = 0.929], clinical pregnancy rate [59.45% vs 58.86%, RR: 1.02 (95%CI, 0.75-1.40), P = 0.877] and multiple pregnancy rate [5.18% vs 5.12%, RR: 1.01 (95%CI, 0.51-2.02), P = 0.971] also did not differ between individualized and standard dosing. There are 24 women who are ongoing pregnancy but do not reach live birth in the completed embryo transfer cycle. The individualized group reported less poor response (31.1% vs 48.7%: P < 0.001), more obtained oocytes (6.80 ± 3.85 vs 5.28 ± 3.22; P < 0.001), less embryos (3.76 ± 2.70 vs 3.16 ± 2.42; P = 0.004), and less good quality embryos (2.61 ± 2.29 vs 2.21 ± 2.05; P = 0.018). When outcomes were compared over the first embryo transfer, ongoing pregnancy rates were 39.0% (128/328) versus 37.2% (124/333), respectively [RR:1.08 (95%CI, 0.79-1.48), P = 0.636], without differences in the other outcomes. There are 7 women who are ongoing pregnancy but do not reach live birth in the first embryo transfer cycle. Limitations, reasons for caution Due to the open-label character, potential selective canceling and small dose adjustments of standard dosing were allowed. This abstract reports on ongoing pregnancy. At the meeting, we will present live birth rates. Wider implications of the findings In women with predicted poor response, an increased dose does not increase ongoing pregnancy rates. A standard dose of 150IU/day is recommended in these women. Trial registration number ChiCTR1900021944

P–694 Natural cycle vs Accumulation of oocytes. Which strategy is better for women with the poor ovarian response (POR)?

Abstract Study question The aim of this study is to determine whether repetitive natural cycles (Strategy A) or oocyte accumulation (Strategy B) is a more effective strategy. Summary answer There was no statistical difference between the strategies however, the number of attempts for successful outcome with strategy A was lower than in strategy B. What is known already For populations with poor ovarian response natural cycles (NC) or modified natural cycles (mNC) with minimal stimulation have been implemented as a preferable option as opposed to conventional ovarian stimulation. Due to the development of advanced vitrification techniques, the accumulation of oocytes has become available. Previous studies (2011, 2013, 2019) suggest that accumulation of oocytes could be a successful alternative to repetitive natural cycles for poor responders aged ≥35 years, showing higher clinical pregnancy rates. Moreover, the embryo-transfer cancellation and miscarriage rate were significantly lower in the oocyte accumulation strategy. Study design, size, duration Present retrospective cohort study included a selection of patients with POR treated from 2019–2020, which were divided into 2 strategies. Strategy A included 324 natural cycles or modified natural cycles with successful oocyte retrievals (Female mean age: 36.3 years). The strategy B consisted of 46 cycles with thawed oocytes that were accumulated through cryopreservation in several attempts (average n = 2,3) prior in NC or mNC (Female mean age: 37.6 years). Participants/materials, setting, methods POR was defined by following criteria: 1) advanced maternal age (≥35 years) or; 2) previous POR (≤3 oocytes with a conventional ovarian stimulation protocol); 3) abnormal ovarian reserve test; The vitrification of the oocytes was performed using Kuwayama method (Cryotech®, Japan), while thawing was performed using Cryotop method (Kitazato®, Japan). Prior to fertilization, oocytes were cultured for 2 hours in IVF medium (Origio®, Denmark). The unsuccessful transvaginal oocyte retrievals (TVOR) were excluded from both strategies. Main results and the role of chance The clinical pregnancy rate per started cycle and per transfer in Strategy A vs Strategy B were 15,4% vs 15,2% and 28.08% vs 20%, respectively. Strategy A seemed to achieve higher rates; however, the difference was not statistically significant (Student’s t-test, p < 0.05). Throughout all TVORs the rate of successful retrieval was 71.7%. The embryo-transfer cancellation rates in Strategy A vs Strategy B were 38,2% vs 8,69%, respectively. With strategy A the average amount of attempts for successful clinical pregnancy was 1.86. With strategy B the average amount of cryopreservations for oocyte accumulation was 2.3. Limitations, reasons for caution The number of patients in strategy B was significantly lower than in strategy A. Larger study with an increased number of samples is necessary to confirm the results. In addition calculation of cost-effectiveness in each strategy. The unsuccessful TVORs were excluded from both strategies, which significantly affects the statistical rates. Wider implications of the findings: This study might help in developing and selecting more appropriate strategies for women with POR. The findings might help to determine the amount of time and attempts required for a successful outcome for patients aged ≥35. It can also be helpful in regulating the financial part of artificial reproductive technology. Trial registration number N/A

P–464 What is the optimal ovarian stimulation (OS) protocol for women who undergo planned oocyte cryopreservation (POC)?

Abstract Study question When repeated cycles of OS for planned oocyte cryopreservation using a standard GnRH antagonist protocol are required, can OS protocol modifications improve oocyte yield? Summary answer Compared to repeating a standard GnRH antagonist protocol, switching to a long GnRH agonist protocol for POC results in a higher number of cryopreserved oocytes. What is known already The total number of cryopreserved oocytes is a key parameter of POC programs because of its association with livebirth. A substantial proportion of women embarking on POC will undergo repeated cycles of OS to reach their desired target number of vitrified oocytes. According to recent guidelines, the GnRH antagonist protocol with GnRH agonist triggering is considered the first choice protocol for POC, because of its safety profile and convenience. However, in women with normal ovarian reserve, the long GnRH agonist protocol results in a higher number of oocytes retrieved. Evidence regarding the optimal protocol for POC is limited. Study design, size, duration This is a single-centre, retrospective cohort study including 283 women who had a first cycle for POC using a standard GnRH antagonist protocol and who requested a second OS cycle to increase their total number of vitrified oocytes for later use. The choice of protocol for the second cycle was left at the discretion of the reproductive medicine specialist. All OS cycles took place between January 2009 and December 2019 in a tertiary referral hospital. Participants/materials, setting, methods After ovarian reserve testing, the first cycle OS was performed using rFSH or HPhMG in a GnRH antagonist protocol. For the second cycle, a GnRH antagonist protocol with or without antagonist pretreatment, or a long GnRH agonist protocol was prescribed. The primary outcome was the number of mature oocytes (MII) vitrified per cycle. Cycle characteristics were compared. Data were assessed by generalized estimating equation (GEE) regression analysis adjusting for covariates. Main results and the role of chance In total, 226 (79.9%) women had a GnRH antagonist protocol and 57 (20.1%) had a long GnRH agonist protocol in their second OS cycle for POC. Overall, mean age was 36.6±2.4 years. The median (CI) number of mature oocytes vitrified after the second OS cycle was significantly higher than that after the first cycle [8 (5–11) vs. 7 (4–10), p < 0.001]. According to GEE multivariate regression, adjusting for relevant confounders, switching from a GnRH antagonist protocol in the first cycle to a long GnRH agonist protocol in the second cycle was the only significant predictor of the number of vitrified oocytes after the subsequent cycle (coefficient 1.59, CI 0.29–2.89, p-value = 0.017). Age, AFC, initial dose and type of gonadotropins did not predict the number of vitrified oocytes. None of the women developed moderate or severe OHSS. Similarly, of 174 women who underwent their first OS cycle with a standard GnRH antagonist protocol, 133 women (76.4%) had the same protocol for their second cycle and 41 women (23.6%) an additional three-day course of GnRH antagonist pretreatment. According to GEE multivariate regression, this protocol modification did not result in more mature oocytes available for vitrification (coefficient –0.25, CI –1.86–1.36, p-value = 0.76). Limitations, reasons for caution These data should be interpreted with caution because of the retrospective design and limited sample. Although more oocytes were obtained with a long GnRH agonist protocol we have no data on livebirth in women returning to use their oocytes to support the choice for a specific OS protocol for POC. Wider implications of the findings: Although oocyte yield in the context of POC is an important parameter that may be modulated by the choice of OS protocol, the ultimate outcome measure of a successful POC program is livebirth after oocyte vitrification. Future research of oocyte parameters reflecting oocyte quality is paramount. Trial registration number Not applicable

O-082 The ratio AMH/antral follicle count varies according to the etiologies of diminished ovarian reserve suggesting differences in follicular health

Abstract Study question Does diminished ovarian reserve (DOR) and its etiology impact the AMH/AFC ratio? Summary answer AMH/AFC ratio varies according to the etiology of DOR in young women, suggesting different impact on the follicular health, and further oocyte quality. What is known already Anti-Müllerian hormone and antral follicle count currently represent the two most accurate markers of the follicular ovarian status. Even though they may diagnose a reduction in the follicular stockpile, low values remain inefficient for predicting poor oocyte quality, in particular in young women. Since AMH is produced by the granulosa cells of follicles ranging from primary to small antral follicles, we hypothesized that the etiology of diminished ovarian reserve might differently impact the follicular health and their capacity of producing this peptide. Study design, size, duration From November 2018 to December 2021, we conducted a monocentric, retrospective study including a total of 484 infertile patients < 37 years with DOR. Participants/materials, setting, methods All patients underwent measurement of AMH levels and AFC. DOR was diagnosed according to the Bologna criteria (AMH < 1.1 ng/mL and AFC < 7). AMH/AFC ratio was compared to values obtained in 154 tubal or male infertility patients matched for age and BMI, with AMH and AFC in the normal ranges. This ratio was studied according to the etiology of DOR: genetic (n = 26), post-chemotherapy (n = 102), idiopathic (n = 215) or ovarian diseases (ovarian cyst or history of ovarian surgery, n = 141). Main results and the role of chance Overall, median age of women with DOR was 30 (18-37) years. As expected, age and BMI were comparable in women with DOR and those having normal ovarian reserve tests. In addition, the AMH/AFC ratio failed to show any difference between these 2 groups (0.143 ± 0.22 vs. 0.166 ± 0.11, NS, respectively). Among women with DOR, the etiology was significantly associated with different AMH/AFC ratio. Indeed, patient with DOR of surgical origin (ovarian diseases group) displayed higher mean values (0.283 ± 0.32 ng/mL/ Foll) when compared with those included in genetic (0.079 ± 0.15 ng/mL/ Foll, p < 0.01), idiopathic (0.103 ± 0.16 ng/mL/ Foll, p < 0.03) or post-chemotherapy (0.084 ± 0.20 ng/mL/ Foll, p < 0.01) groups. Moreover, genetic and post-chemotherapy DOR was also associated with lower AMH/AFC ratio in comparison with idiopathic DOR. Limitations, reasons for caution Despite interesting results, the retrospective nature of the present study may represent a limitation. Moreover, AMH/AFC ratio constitute an indirect method for assessing per follicle AMH production. We hypothesized that this ratio might reflect the follicular health. Its impact on natural conception and assisted reproductive technologies outcome is not known. Wider implications of the findings AMH/AFC ratio may represent an innovative tool aiming to indirectly assess follicular health and possibly oocyte quality in young women with DOR. The etiology of DOR differently impacts the follicular function as reflected by AMH/AFC ratio. Further data on live birth rates following natural or medically assisted pregnancies is needed. Trial registration number N/A

Impact of Bariatric Surgery-Induced Weight Loss on Ovarian Reserve in Women with Obesity: A Systematic Review

Background: Due to exponential obesity prevalence, the number of bariatric surgery (BS) procedures has considerably increased. BS improves ovulatory function and natural fertility in some women. However, its effect on ovarian reserve is poorly known. The objective of this study was to carry out a systematic review of the literature to evaluate the impact of BS on ovarian reserve for women with obesity. Methods: In this systematic review, PubMed and EMBASE databases were searched for studies evaluating the results of ovarian reserve tests in obese women before and after BS, and published between January 1st, 2000, and March 1st, 2020. Results: Eight studies were included, totaling 355 women with serum antimullerian hormone (AMH) levels evaluated before and after BS. The majority of currently available studies report a decrease in AMH levels occurring 6 and/or 12 months after surgery, which could suggest an ovarian reserve impairment following BS. Conclusions: Although the pathophysiological mechanisms are poorly understood, this alteration raises concerns regarding long-term fertility following BS. Larger prospective controlled cohort studies will be necessary to provide a conclusion about the potential effect of BS on ovarian reserve. If a deleterious effect is confirmed, oocyte cryopreservation before surgery could be discussed.

Fertility preservation in childhood and adolescent female tumor survivors

To assess the proportion of female childhood and adolescent tumor survivors who could benefit from oocyte cryopreservation. Case series of female childhood and adolescent tumor survivors referred for fertility counseling. A referral cancer center and an infertility unit of an academic hospital. Young female childhood and adolescent tumor survivors who received gonadotoxic treatments. Patients were prescribed tests of ovarian reserve and a personalized counseling was given. Oocyte cryopreservation was considered in subjects aged ≥18 years who were diagnosed with diminished ovarian reserve (DOR) (antimüllerian hormone level <2 ng/mL or total antral follicle count ≤10). Rate of women with DOR who stored their oocytes. Ninety out of 126 evaluated women completed the assessments. We documented preserved ovarian reserve, DOR, and premature ovarian insufficiency in 36 (40%), 35 (39%), and 19 (21%) cases, respectively. Overall, 13 subjects with DOR were eligible for oocyte cryostorage, of whom 9 (69%) underwent the procedure. Considering the whole cohort of evaluated young women (n = 90), the rate of those who had egg freezing was 10%. Finally, nine women started seeking pregnancy after the counseling (six with DOR), and seven of them became pregnant. When the data were analyzed separately according to most gonadotoxic treatments, considerable differences emerged but the evidence did not support the idea that counseling should be restricted to particular subgroups of women. Ovarian reserve impairment is common in female childhood and adolescent tumor survivors. Postcancer oocyte cryopreservation may be part of the armamentarium of fertility preservation options.

Characterization of micro-RNA in women with different ovarian reserve

Women undergoing infertility treatment are routinely subjected to one or more tests of ovarian reserve. Therefore, an adequate assessment of the ovarian reserve is necessary for the treatment. In this study, we aimed to characterize the potential role of microRNAs (miRNAs) as biomarkers for women with different ovarian reserves. A total of 159 women were recruited in the study and classified according to their anti-Müllerian hormone (AMH) level into three groups: (1) low ovarian reserve (LAMH, n = 39), (2) normal ovarian reserve (NAMH, n = 80), and (3) high ovarian reserve (HAMH, n = 40). SurePrint Human miRNA array screening and reverse transcription-quantitative PCR (RT-qPCR) were respectively employed to screen and validate the miRNA abundance level in the three tested groups. Compared with NAMH, the abundance level of 34 and 98 miRNAs was found to be significantly altered in LAMH and HAMH, respectively. The abundance level of miRNAs was further validated by RT-qPCR in both, the screening samples as well as in an independent set of validation samples. The abundance levels of the validated miRNAs were significantly correlated with the AMH level. The best AUC value for the prediction of the increase and decrease in the AMH level was obtained for the miR-100-5p and miR-21-5p, respectively. The level of miRNAs abundance correlates with the level of AMH, which may serve as a tool for identifying women with a different ovarian reserve and may help to lay the ground for the development of novel diagnostic approaches.

Impact of ambient temperature on ovarian reserve

To examine the association between ambient temperature and antral follicle count (AFC), a standard measure of ovarian reserve. Prospective cohort study. Fertility center at an academic hospital in the northeastern United States. 631 women attending the Massachusetts General Hospital Fertility Center (2005-2015) who participated in the Environment and Reproductive Health Study. Daily temperature at the women's residential address was estimated for the 90 days before their antral follicle scan using a spatially refined gridded climate data set. We evaluated the associations between temperature and AFC using Poisson regression with robust standard errors, adjusting for relative humidity, fine particulate matter exposure, age, education, smoking status, year and month of AFC, and diagnosis of diminished ovarian reserve and ovulation disorders. Antral follicle count as measured with transvaginal ultrasonography. A 1°C increase in average maximum temperature during the 90 days before ovarian reserve testing was associated witha -1.6% (95% confidence interval [CI], -2.8, -0.4) lower AFC. Associations remained negative, but were attenuated, for average maximum temperature exposure in the 30 days (-0.9%, 95% CI, -1.8, 0.1) and 14 days (-0.8%, 95% CI, -1.6, 0.0) before AFC. The negative association between average maximum temperature and AFC was stronger in November through June than during the summer months, suggesting that timing of heat exposure and acclimatization to heat may be important factors to consider in future research. Exposure to higher temperatures was associated with lower ovarian reserve. These results raise concern that rising ambient temperatures worldwide may result in accelerated reproductive aging among women.

MOTHER Study: A Multicenter Observational, Retrospective Study to Determine Coorelation Between Physical CHaracteristics and Ovarian REserve Markers in Sub-feRtile Women.

The physical characteristics which are known to affect the ovarian reserve are age, body mass index (BMI), occupational exposures, age at menarche and menstrual cycle length. A correlation between different physical characteristics and the ovarian reserve will help to identify areas which need to be tackled to increase the chances of fertility of women in India. In this retrospective, observational study, namely the MOTHER Study, data of women between 18 and 45years of age, attending the selected fertility centers across different states in India were taken for evaluation. Demographic information along with information on factors potentially related to fertility like age of menarche, menstrual cycle length and occupational factors were collected by review of medical records at screening visit. Most recent AMH assay and antral follicle count (AFC) where the subject has not taken any contraceptives 12months prior to the test were collected. Age of woman, years of marriage, years of infertility and smoking have shown effect on ovarian reserve testing like AMH and AFC. The other physical characteristics which were evaluated and considered to affect the ovarian reserve like body mass index BMI, occupational exposures, age at menarche and menstrual cycle length have not shown statistically significant correlation. Age of woman and years of infertility are inversely proportional to ovarian reserve markers, namely AMH and AFC. Addictions like smoking and alcohol affect ovarian reserve.

The Cyclic Self: Menstrual Cycle Tracking as Body Politics

Tracking in/fertility—through ovulation biosensing, menstrual and perimenopausal apps, and ovarian reserve testing—is becoming increasingly commonplace amongst relatively privileged women in the Global North. Taking place on and through platforms comprised of devices, bodies, and discourses, such self-tracking articulates forms of in/fertility and reproductive futures that are, we argue, closely entwined with emerging forms of biomedical capitalization. While reproductive medicine focused on the creation of children has been entwined with corporate interests since the development of in vitro fertilization in the 1980s, fertility as an asset, or future value, is increasingly targeted by the new innovation sectors as a specific capacity, separable from reproduction per se, in which women should invest if they are not to fall prey to incipient infertility. Synthesizing our separate empirical work in this field, this paper theorizes the connections between the emergence of self-tracking logics and cultures, the burgeoning of consumer-oriented, clinical services, and contemporary social anxieties around fertility decline. Even in countries such as Australia and the United Kingdom, where birth rates are stable, (some) women’s fertility is being refigured as precious and vulnerable, something to be tracked, documented, and attended to in the name of individual future happiness and fulfilment. Women with enough financial and cultural capital are encouraged to monitor their periods, come to know their ovulation patterns, and become aware of their ovarian reserve, and, importantly, to act prudently on such knowledge to safeguard their reproductive futures.

Incipient Infertility: Tracking Eggs and Ovulation Across the Life Course

Tracking in/fertility—through ovulation biosensing, menstrual and perimenopausal apps, and ovarian reserve testing—is becoming increasingly commonplace amongst relatively privileged women in the Global North. Taking place on and through platforms comprised of devices, bodies, and discourses, such self-tracking articulates forms of in/fertility and reproductive futures that are, we argue, closely entwined with emerging forms of biomedical capitalization. While reproductive medicine focused on the creation of children has been entwined with corporate interests since the development of in vitro fertilization in the 1980s, fertility as an asset, or future value, is increasingly targeted by the new innovation sectors as a specific capacity, separable from reproduction per se, in which women should invest if they are not to fall prey to incipient infertility. Synthesizing our separate empirical work in this field, this paper theorizes the connections between the emergence of self-tracking logics and cultures, the burgeoning of consumer-oriented, clinical services, and contemporary social anxieties around fertility decline. Even in countries such as Australia and the United Kingdom, where birth rates are stable, (some) women’s fertility is being refigured as precious and vulnerable, something to be tracked, documented, and attended to in the name of individual future happiness and fulfilment. Women with enough financial and cultural capital are encouraged to monitor their periods, come to know their ovulation patterns, and become aware of their ovarian reserve, and, importantly, to act prudently on such knowledge to safeguard their reproductive futures.

Outdoor air pollution and diminished ovarian reserve among infertile Korean women

BackgroundMounting evidence implicates an association between ambient air pollution and impaired reproductive potential of human. Our study aimed to assess the association between air pollution and ovarian reserve in young, infertile women.MethodsOur study included 2276 Korean women who attended a single fertility center in 2016–2018. Women’s exposure to air pollution was assessed using concentrations of particulate matter (PM10 and PM2.5), nitrogen dioxide (NO2), carbon monoxide (CO), sulfur dioxide (SO2), and ozone (O3) that had been collected at 269 air quality monitoring sites. Exposure estimates were computed for 1, 3, 6, and 12 months prior to the ovarian reserve tests. Anti-Müllerian hormone (AMH) ratio (defined as an observed-to-expected AMH based on age) and low AMH (defined as < 0.5 ng/mL) were employed as indicators of ovarian reserve. We included a clustering effect of 177 districts in generalized estimating equations approach. A secondary analysis was conducted restricting the analyses to Seoul residents to examine the association in highly urbanized setting.ResultsThe mean age was 36.6 ± 4.2 years and AMH level was 3.3 ± 3.1 ng/mL in the study population. Average AMH ratio was 0.8 ± 0.7 and low AMH was observed in 10.3% of women (n=235). The average concentration of six air pollutants was not different between the normal ovarian reserve and low AMH groups for all averaging periods. In multivariable models, an interquartile range (IQR)-increase in 1 month-average PM10 was associated with decrease in AMH ratio among total population (β= −0.06, 95% confidence interval: −0.11, 0.00). When we restrict our analysis to those living in Seoul, IQR-increases in 1 and 12 month-average PM2.5 were associated with 3% (95% CI: −0.07, 0.00) and 10% (95% CI: −0.18, −0.01) decrease in AMH ratio. The ORs per IQR increase in the six air pollutants were close to null in total population and Seoul residents.ConclusionsIn a cohort of infertile Korean women, there was a suggestive evidence of the negative association between ambient PM concentration and ovarian reserve, highlighting the potential adverse impact of air pollution on women’s fertility.

Ethnicity/Race and Age-Specific Variations of Serum AMH in Women—A Review

Purpose of ReviewIn this review, we summarize ethnic/race- and age-related variation in AMH and discuss the underpinnings behind these differences.Recent findingsAnti-mullerian hormone (AMH) has become a widely used method of ovarian reserve testing over the last 15 years. Numerous studies have shown substantial ethnic/race and age-related differences. When compared to age-matched Caucasian women, AMH levels tend to be lower in black and Hispanic women. Chinese women tend to have significantly greater AMH levels prior to age 25 than Caucasian women. When considering subpopulations within ethnicities, at least one study noted lower AMH levels among Maya women compared to other Hispanic women. Age exhibits a positive trend with AMH up until at least 25 years of age with a consistent decline after 34 years of age extending to menopause.SummaryAMH levels are highly variable among ethnicities and race with higher age-matched levels typically seen in Caucasian women. Age does not exhibit a consistent linear relationship with AMH, but a consistent decline is seen starting in the third decade of life and proceeding to menopause.

Analysis of factors associated with ovarian reserve in a group of poor responders to in vitro fertilization: A cross-sectional study.

BackgroundPoor ovarian reserve and a high rate of pregnancy failure associated with low quality and quantity of oocytes are observed in poor responders to in vitro fertilization.ObjectiveTo assess the effect of age, body mass index (BMI), endometriosis, and history of ovarian surgery on ovarian reserve in a group of poor responders.Materials and Methods In this cross-sectional study 749 women who referred to Yasmin Clinic of Dr. Cipto Mangunkusumo National General Hospital from January 2013 to June 2017 were enrolled. Two definitions of poor responders and Poseidon criteria and consecutive sampling techniques were used. Participants were divided into good and poor responder groups based on the ovarian reserve test; participant with oocyte 3 was classified as a poor responder. Based on this, 188 participants with nine (4-47) oocytes were included in the poor responder group. While, good responder comprised of two (0-3) oocytes.ResultsAge and anti-Mullerian hormone level (AMH) were significantly associated with ovarian reserve in the poor-responder group (p 0.001). However, in multivariate analyses, age was the only significant predictor of ovarian response in the poor-responder group (p = 0.004). While endometriosis was the significant predictor of Poseidon groups 1 and 4, surgical history was the significant predictor of Poseidon groups 2 and 3. Meanwhile, an increase in BMI decreased the risk of classification under Poseidon group 3.ConclusionAge, AMH, BMI, endometriosis, and history of ovarian surgery affected the risk of classification of the Poseidon group.

Sperm parameters and anti-M\xfcllerian hormone remain stable with Helicobacter pylori infection: a cross-sectional study

Background and aimsIt has been reported that Helicobacter pylori (HP) infection was more prevalent in infertile populations. HP infection could lead to decreased sperm parameters, and treating the HP infection could improve the quality of sperm. However, studies investigating the relationship between infertility and HP infection are still limited, and more evidence is required. Therefore, we performed the present study to investigate the impact of HP infection on sperm quality in males and on ovarian reserve in females.MethodsA total of 16,522 patients who visited the Second Hospital of Zhejiang University from January 2016 to June 2019 due to abdominal discomfort and underwent a 13/14C-urea breath HP test were included in this retrospective cross-sectional study. Among them, 565 had performed sperm analysis or ovarian reserve tests in the past three months and were involved for further analyses. Sperm parameters were examined with a computer-assisted sperm analysis system, and serum anti-Müllerian hormone (AMH) and sex hormones were tested with an electrochemiluminescence method.ResultsAmong 363 patients who underwent the sperm test, 136 (37.47%) had HP infection. Among 202 patients who underwent the AMH test, 55 (27.23%) had HP infection. There was no difference in sperm concentration and motility between the HP+ and HP− groups (P > 0.05). Further subgroup analyses stratified into 5-year age groups confirmed that there was no significant difference in sperm parameters (P > 0.05). When pooled with previously published data, no significant difference in sperm concentration or motility was found (P > 0.05). Meanwhile, this study found that the serum AMH level was similar between the HP+ and HP− groups (P > 0.05). Further subgroup analyses confirmed that there was no significant difference in serum AMH level (P > 0.05).ConclusionsThere were no differences in sperm parameters and AMH levels based on history of HP infection among Chinese patients.

AMH assessment five or more years after an initially low AMH level

PurposeAnti-Müllerian hormone (AMH) is a biomarker reflecting ovarian reserve. A low AMH level before 39 years may be associated with a risk of menopause between 40 and 45 years. The risk of onset of premature ovarian insufficiency (POI) is, however, poorly documented. The objective of the study was to determine the prevalence of POI 5–10 years after an AMH assay below 8 pmol/L. MethodsWe included women aged younger than 36 years who underwent a complete workup for infertility between January 2008 and December 2013 at the University Hospital and had an AMH level less than 8 pmol/L. In 2018, 47 of these women were assessed clinically, and 21 of them agreed to undergo an ovarian reserve test. ResultsThe prevalence of POI after at least 5 years was 8/47, or 17 % [8 %–31 %]. The median time to diagnosis was 5.1 years [2.9–7.3]. There was a significant difference at T0 in the regularity of cycles between the two groups (p = 0.024) and in their baseline serum AMH level: 6.0 pmol/L in the non-POI group vs 4.2 pmol/L in the POI group (p = 0.002). ConclusionSerum AMH < 8 pmol/L before the age of 36 years appears to be a risk factor for POI. These women require regular follow-up, especially if their cycles are irregular.