Ovarian Stimulation For IVF Research Articles

O-219 Explainable artificial intelligence (XAI) to determine the follicle sizes on trigger day that maximize mature oocyte yield

Abstract Study question Which follicle sizes on trigger day (TD) are key to obtaining mature oocytes, embryos, and blastocysts, thereby enhancing live birth rates? Summary answer Follicles sized 13-18mm are most likely to yield mature oocytes. Live birth rate (LBR) was increased with a greater proportion of follicles in this range. What is known already At the time of oocyte retrieval, follicles that are either too small or too large are less likely to yield mature oocytes. However, there is only limited data examining which follicle sizes on TD administration are optimally sized to yield mature oocytes, nor any data examining whether live birth rates are impacted. Explainable artificial intelligence (XAI) offers a valuable opportunity to leverage clinical data to determine the range of follicle sizes that are most likely to yield mature oocytes and lead to improved downstream outcomes. Study design, size, duration A retrospective study incorporating 19,082 patients undergoing their first IVF/ICSI cycle (2005-2023) across 11 European clinics. Follicle sizes on TD were related to oocyte maturity (14,140 patients), fertilization (17,822 patients), high-quality blastocyst development (17,488 patients), and pregnancy outcomes (12,672 patients). Secondary analyses included stratification by age (>35 years: 4,717 patients; ≤35 years: 5,707), and suppressant protocol (GnRH agonist: n = 5,420 patients; GnRH antagonist: n = 3,982). Participants/materials, setting, methods An ensemble-based XAI model, developed through ‘internal-external validation’, was trained, Bayesian optimized, and independently iteratively tested on hold-out clinic datasets. The model determined follicle sizes contributing most to successful laboratory outcomes by harnessing permutation importance and ‘SHAP’ values. Model performance was evaluated and optimized for mean absolute error (MAE). The top 50% contiguous cohort of influential follicle sizes on TD were identified, and further validated through analysis of follicle sizes on preceding days. Main results and the role of chance XAI analysis revealed that follicles sized 13-18mm on TD were most influential in yielding mature oocytes, especially those sized 15-18mm (MAE: 3.60 ±0.35). Predictive follicle sizes from scans 1-2 days preceding TD administration were consistent with expected mean follicle growth rates. For high-quality blastocysts, follicles sized 14-20mm were contributory, narrowing to 15-18mm in the subset of patients where oocytes had been confirmed to be mature. In hCG-triggered cycles, follicles sized 12-19mm were most likely to yield mature oocytes in GnRH antagonist cycles, whereas follicles sized 14-20mm were most contributory in GnRH agonist cycles. In patients ≤35 years, follicles 13-18mm were most contributory, whereas a wider range of follicles (11-20mm) were contributory in patients >35 years. In line with current practice, having three lead follicles ≥17mm on TD was associated with a median improvement in mature oocyte yield of 10% versus those that did not (p < 0.0001). By comparison, maximizing the proportion of follicles on TD within the optimal size range could better improve mature oocyte yield, for example, by 42% when at least 70% of follicles were sized 15-18mm (p < 0.0001). Likewise, LBR improved as the proportion of follicles sized 13-18mm was increased (<10%: 23.3%; 10-20%: 25.7%; 20-30%: 28.8%; 30-40%: 31.6%). Limitations, reasons for caution These data could help guide when to administer the trigger to optimize clinical outcomes, however prospective assessment of different TD strategies based on the proportion of follicles within the optimal follicle size ranges identified in comparison to current practice based on lead follicle size is required prior to clinical adoption. Wider implications of the findings These findings provide a data-driven approach to personalizing ovarian stimulation in IVF. The findings generated by applying an XAI model could assist clinicians in optimizing TD timing, potentially enhancing clinical outcomes by moving beyond the conventional focus on lead follicle size. Trial registration number not appicable

Resistant ovary syndrome: Two case reports and a literature review of effective controlled ovarian stimulation in IVF.

Resistant ovary syndrome (ROS) represents a rare reproductive endocrine disorder that is predominantly associated with infertility, characterized by heightened endogenous gonadotropin levels in the presence of a normal ovarian reserve. Patients with ROS typically exhibit a poor response to exogenous gonadotropins during controlled ovarian stimulation (COS). Due to the absence of a universally accepted effective COS protocol, this study aims to contribute to the existing body of literature by detailing 2 successful pregnancies achieved through conventional in vitro fertilization (c-IVF) in patients with ROS, and through retrospective analysis, seeks to elucidate the factors contributing to the successful ovarian stimulation in these cases, with the ultimate goal of establishing clinical guidelines for ROS management. The central challenge addressed in this study pertains to the effective induction of oocyte maturation during c-IVF COS in ROS patients. The study focuses on 2 infertile women diagnosed with ROS who sought to conceive via c-IVF. The patients were subjected to a COS protocol involving pituitary downregulation followed by ovarian stimulation using recombinant follicle-stimulating hormone (r-FSH) and human menopausal gonadotropin (HMG), preceded by 3 cycles of hormone replacement therapy (HRT) pretreatment. The proposed protocol elicited a favorable ovarian response, culminating in the retrieval of numerous mature oocytes and the development of multiple viable embryos via c-IVF, ultimately leading to successful live births post-embryo transfer. Our study suggests that the outlined COS protocol may serve as a viable treatment option for ROS patients aspiring to conceive through c-IVF, thereby potentially expanding the therapeutic repertoire for this challenging condition.

Pretreatment with oral contraceptive pills in women with PCOS scheduled for IVF: a randomized clinical trial

Abstract STUDY QUESTION What is the effect of pretreatment with oral contraceptive pills (OCPs) on oocyte and embryo quality and pregnancy rates in women with polycystic ovary syndrome (PCOS) scheduled for IVF/ICSI cycles? SUMMARY ANSWER In women with PCOS who underwent a first or second IVF/ICSI cycle with a GnRH antagonist protocol and were randomized to start ovarian stimulation immediately, the quality of cleavage-stage embryos was non-inferior to pretreatment with OCP. WHAT IS KNOWN ALREADY PCOS in Asian populations is characterized by high levels of circulating LH in the early follicular phase. Previous studies indicated that inappropriately high LH levels might affect oocyte maturation and fertilization rates, and impaired embryo quality, consequently resulting in higher rates of impaired pregnancy and miscarriage in women with PCOS. OCPs are frequently used as pretreatment to lower LH levels in PCOS patients. STUDY DESIGN, SIZE, DURATION We performed a randomized controlled trial. After informed consent, women diagnosed with PCOS scheduled for their first or second IVF/ICSI cycle with a GnRH antagonist protocol were randomized to receive OCPs (OCP group) or start ovarian stimulation immediately, regardless of the day of the menstrual cycle (non-OCP group). Using a non-inferiority hypothesis, the sample size was calculated at 242 women. The study lasted from 7 February 2018 to 31 August 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 242 infertility patients with PCOS undergoing the first or second cycle of IVF or ICSI were enrolled and randomized into two groups. In the OCP group, recombinant FSH was started on Day 7 of the washout period after pretreatment with OCP. In the non-OCP group, recombinant FSH was started immediately regardless of the day of the menstrual cycle. All participants received standardized GnRH antagonist ovarian stimulation. The freeze-all strategy was applied to all participants. The primary outcome was the number of good-quality embryos on Day 3 after insemination. Secondary outcomes included the rates of blastocyst formation, implantation, clinical pregnancy, and live birth from the first frozen/warmed embryo transfer cycles and cumulative live birth rates. MAIN RESULTS AND THE ROLE OF CHANCE We randomized 242 women to receive OCP (n = 121) or start immediately with ovarian stimulation (n = 121). The number of good-quality embryos on Day 3 in the OCP group was non-inferior to the non-OCP group (OCP group versus non-OCP group, 6.58 ± 4.93 versus 7.18 ± 4.39, AD −0.61, 95% CI: −1.86 to 0.65, P = 0.34). The rates of blastocyst formation (55.4% versus 52.9%, relative risk (RR) 1.11, 95% CI: 0.96 to 1.28, P = 0.17), implantation (63.0% versus 65.5%, RR 0.90, 95% CI: 0.53 to 1.53, P = 0.79), clinical pregnancy (67.9% versus 68.8%, RR 0.96, 95% CI: 0.54 to 1.71, P = 1.0), and live birth rate (52.8% versus 55.1%, RR 0.92, 95% CI: 0.53 to 1.56, P = 0.79) of the first frozen/warmed embryo transfer cycles were all comparable between the OCP and non-OCP group, respectively. Cumulative live birth rates were also similar in the OCP and non-OCP groups (78.3% versus 83.5%, respectively RR 0.71, 95% CI: 0.36 to 1.42, P = 0.39). LIMITATIONS, REASONS FOR CAUTION Only patients with PCOS in Southern China were recruited. Therefore, caution is necessary when generalizing our results to all such patients with PCOS. Also, since a freeze-only strategy was used, the results of this study are only applicable when infertile women with PCOS undergo the freeze-only method. The obvious treatment difference between the two groups meant that the study was designed as an open-label study for women and doctors. The study had a randomized controlled design that minimized bias. WIDER IMPLICATIONS OF THE FINDINGS Pretreatment with OCPs to lower LH levels in patients with PCOS before ovarian stimulation in IVF or ICSI cycles may not improve the quality of cleavage-stage embryos. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the National Key Research and Development Program of China (No. 2023YFC2705503). This study was supported in part by the Investigator-Initiated Studies Program (grant from MSD and Organon). BWM reports consultancy, travel support, and research funding from Merck. He reports consultancy from Organon and Norgine, and also reports holding stock from ObsEva. No conflicts of interest are declared for the other authors. TRIAL REGISTRATION NUMBER Chinese Clinical Trial Registry (No. chiCTR1800014822). URL: https://www.chictr.org.cn/showproj.html?proj=25280 TRIAL REGISTRATION DATE 7 February 2018. DATE OF FIRST PATIENT’S ENROLLMENT 22 February 2018.

LH supplementation in IVF: human nature, politics, and elephants in the room.

Luteinizing hormone (LH) is present throughout the natural follicular phase. However, the debate is still not settled on whether LH is needed during ovarian stimulation in IVF. This commentary looks at the evolution of this debate, mentioning three elephants in the room that were ignored by the Pharma industry, professional organizations, and clinicians alike: 1. The different endocrinology between the long agonist and the antagonist protocols. 2. The fixed dose of the two most widely commercially available antagonist preparations, namely cetrorelix and ganirelix. 3. The fact that most research in this area uses population-based criteria, ignoring endocrine parameters. Individual genetics of the LH receptor gene may also serve to individualize LH needs during stimulation; however, the jury is still out regarding this approach. CONCLUSIONS: Individual endocrine and genetics parameters may shed meaningful light on the question of LH supplemental during ovarian stimulation.

P-616 Evaluation of salivary ELISA for Oestradiol and Progesterone monitoring in IVF patients

Abstract Study question How do salivary E2 and P correlate with serum determinations across ovarian stimulation (OS) for IVF and artificial endometrial preparation cycles for embryo transfer? Summary answer Saliva-blood correlations were higher for E2 than for P. E2 saliva-blood ratios were patient-dependent. High serum P cases on trigger day could be identified. What is known already Steroid hormone concentrations in saliva are lower than in serum, even if the hormone is predominantly free. Therefore, quantitative assays need to be as sensitive as possible. Saliva-based assessments are a reliable and proven method for quantifying female hormone levels in premenopausal women during the natural cycle while being very precise and painless for patients. However, the cumulative experience in ovarian stimulation is relatively low. A recent study including 652 pairs of saliva-serum E2 samples reported correlations between 0.68 and 0.91, while 237 pairs of samples for P showed correlations ranging from -0.02 to 0.22 (Sakkas et al, 2020). Study design, size, duration Prospective cohort study including 300 saliva-blood pair samples from 120 patients undergoing OS for IVF (n = 90) or artificial endometrial preparation for embryo transfer (n = 30) between February and October 2022. Data were collected at each of 3 points of OS: early (days 1-5), mid (days 6-9), and trigger. Patients following endometrial preparation collected just one sample on the day of embryo transfer Participants/materials, setting, methods Thirty expected poor responders, 30 normal, and 30 expected high responders according to ovarian reserve evaluation were included. Two saliva samples per blood sample were collected: immediately after waking up, and at the clinic just before or after the blood sample was taken. Saliva samples were stored at -20ºC and shipped to Mint Diagnostics (Kent, UK) for analysis of salivary E2 and P4 Main results and the role of chance Saliva-blood E2 correlations (Spearman) were 0.68 (fasting) and 0.69 (clinic). 72% of individuals showed saliva-serum correlations > 0.8. Correlations improved when controlling for subgroup (low, normal, high responders). P4 saliva-blood correlations (Spearman) were 0.44 (fasting) and 0.29 (clinic). 41% of individuals showed correlations >0.8 on fasting samples, and 33% on clinic samples. There was a high variance of individual correlations (0-1), which were dependent on ovarian response subgroups (p < 0.05). A multivariable approach was developed to identify patients with a serum P4>1.5 ng/mL the day of trigger (n = 11) with clinic samples showing 81% sensitivity and 91% specificity and fasting samples showing 83% and 91% respectively demonstrating the possibility of shifting hormone analysis to the home rather than the clinic. Eighteen of 30 (60%) saliva samples collected on the day of ET on patients under hormonal replacement therapy showed values out of the assay range (>5000 pg/mL). Therefore, no correlations could be estimated. Limitations, reasons for caution Detection of patients with high P4 on the day of trigger was limited due to a short number of cases. No conclusions could be drawn in HRT patients for embryo transfer due to high salivary P4 values. Wider implications of the findings The current study shows that salivary monitoring of E2 and P4 is feasible. This more friendly non-invasive method could allow frequent hormone monitoring without the need for appointments at the clinic and for phlebotomy, thus resulting in more convenience for both the clinics and the patients. Trial registration number NCT05184777

P-630 Comparison of follitropin delta versus follitropin alfa in progestin-primed ovarian stimulation in IVF

Abstract Study question Is there a difference in a clinical outcome between using follitropin delta and follitropin alfa undergoing a progestin primed ovarian stimulation (PPOS) protocol? Summary answer There was no difference between follitropin delta and follitropin alfa in terms of pregnancy rates. What is known already Follitropin delta (REKOVELLE, Ferring Pharmaceuticals, Switzerland) is the first recombinant human follicle-stimulating hormone (FSH) using the algorithm-based individualized dosing regimen while reducing the risk of ovarian hyperstimulation syndrome (OHSS) as compared with conventional dosing strategies. The efficacy and safety of follitropin delta has been demonstrated in randomized controlled trials (RCTs). Study design, size, duration We performed a retrospective analysis of 645 patients who underwent ovarian stimulation by a PPOS protocol using follitropin delta or follitropin alfa between April 2022 and August 2022. (325 patients using follitropin delta and 320 patients using follitropin alfa, respectively.) Participants/materials, setting, methods 325 cycles of women who used follitropin delta were compared to 320 cycles of women who used follitropin alfa. The following outcomes were analysed; fertilized rate, 2 pronuclear embryo rate, good quality embryo rate, blastocyst rate, good quality blastocyst rate. A total of 499 women who underwent embryo transfer in cryo cycles using natural cycle or hormone replacement cycle were analysed about biochemical pregnancy rate, clinical pregnancy rate. Main results and the role of chance Baseline demographics for 325 women in follitropin delta group and 320 women in follitropin alfa were: age, 35.1±4.3 years and 35.2±4.3 years; number of previous IVF cycles, 1.6±1.6 and 1.7±1.7, respectively. The laboratory data were: fertilization rate, 81.4% and 80.1%, 2 pronuclear embryo rate, 73.9% and 71.5%, good quality cleavage stage embryo rate, 59.4% and 55.9%, blastocyst rate, 58.9% and 55.7%, good quality blastocyst rate, 41.3% and 38.7%, respectively. Only good quality cleavage stage embryo rate and good quality blastocyst rate were significantly higher (P < 0.05) in follitropin delta group. A vitrified-warmed embryo transfer was performed for 257/325 women (79.1%) and 242/320 women (75.6%) and subsequent positive β-human chorionic gonadotropin (βhCG) reported for 218/621 cycles (35.1%) and 194/570 cycles (34.0%), respectively. Ongoing pregnancy rate after embryo transfer were 19.2% (n = 119) and 19.6% (n = 112) and cumulative ongoing pregnancy rate were both 46.3%. Mild OHSS was reported for 131 women (40.3%) and 170 women (53.1%), respectively (P = 0.07). Limitations, reasons for caution This is a non-controlled, retrospective study. Wider implications of the findings The present study shows that in addition to reducing the OHSS risk, follitropin delta in its individualised fixed-dose regimen has the potential to improve the quality of embryos although there was no significant difference in clinical outcomes. Trial registration number not applicable

The HERA (Hyper-response Risk Assessment) Delphi consensus definition of hyper-responders for in-vitro fertilization.

To provide an agreed upon definition of hyper-response for women undergoing ovarian stimulation (OS)? A literature search was performed regarding hyper-response to ovarian stimulation for assisted reproductive technology. A scientific committee consisting of 5 experts discussed, amended, and selected the final statements in the questionnaire for the first round of the Delphi consensus. The questionnaire was distributed to 31 experts, 22 of whom responded (with representation selected for global coverage), each anonymous to the others. A priori, it was decided that consensus would be reached when ≥ 66% of the participants agreed and ≤ 3 rounds would be used to obtain this consensus. 17/18 statements reached consensus. The most relevant are summarized here. (I) Definition of a hyper-response: Collection of ≥ 15 oocytes is characterized as a hyper-response (72.7% agreement). OHSS is not relevant for the definition of hyper-response if the number of collected oocytes is above a threshold (≥ 15) (77.3% agreement). The most important factor in defining a hyper-response during stimulation is the number of follicles ≥ 10mm in mean diameter (86.4% agreement). (II) Risk factors for hyper-response: AMH values (95.5% agreement), AFC (95.5% agreement), patient's age (77.3% agreement) but not ovarian volume (72.7% agreement). In a patient without previous ovarian stimulation, the most important risk factor for a hyper-response is the antral follicular count (AFC) (68.2% agreement). In a patient without previous ovarian stimulation, when AMH and AFC are discordant, one suggesting a hyper-response and the other not, AFC is the more reliable marker (68.2% agreement). The lowest serum AMH value that would place one at risk for a hyper-response is ≥ 2ng/ml (14.3pmol/L) (72.7% agreement). The lowest AFC that would place one at risk for a hyper-response is ≥ 18 (81.8% agreement). Women with polycystic ovarian syndrome (PCOS) as per Rotterdam criteria are at a higher risk of hyper-response than women without PCOS with equivalent follicle counts and gonadotropin doses during ovarian stimulation for IVF (86.4% agreement). No consensus was reached regarding the number of growing follicles ≥ 10mm that would define a hyper-response. The definition of hyper-response and its risk factors can be useful for harmonizing research, improving understanding of the subject, and tailoring patient care.

P-706 Improved prediction of the number of oocytes retrieved using automated-3D ultrasound compared to manual-2D ultrasound on the day of triggering final oocyte maturation

Abstract Study question Does the number of follicles ≥11mm differ when measured by manual-2D or automated-3D ultrasound and which method predicts the number of oocytes collected more accurately? Summary answer Manual-2D and automated-3D ultrasound find similar numbers of follicles ≥11mm. Automated-3D ultrasound has a higher predictive ability regarding the number of oocytes collected. What is known already Accurate assessment of the size and number of follicles during ovarian stimulation is important to determine the optimum day of triggering final oocyte maturation and subsequent oocyte retrieval, in order to achieve the maximum number of mature oocytes. Moreover, the number of follicles ≥11mm on the day of triggering final oocyte maturation, has been used as a criterion to identify women at risk of Ovarian Hyperstimulation Syndrome. Automated-3D ultrasound follicle size and count measurement has been proposed as a valid alternative to 2D ultrasound measurement, but its predictive ability regarding number of oocytes collected has not been compared. Study design, size, duration Prospective observational cohort study performed between 12/2020 and 07/2021 in a single ART center including 93 women undergoing COS. On the day of triggering final oocyte maturation, 3D-ultrasound (SonoAVC;GE Medical Systems) and traditional 2D-ultrasound were used to assess the number and size of follicles. Participants/materials, setting, methods Patients underwent ovarian stimulation with recombinant-FSH and GnRH antagonists. Triggering of final oocyte maturation was performed when three follicles ≥17mm were present on 2D ultrasound. The number of follicles ≥11mm assessed with manual-2D and automated-3D ultrasound on the day of triggering was compared. Linear regression analysis was performed with dependent variable the number oocytes retrieved and independent variables the number of follicles ≥11mm (2D-ultrasound) as well as the number of follicles ≥11mm (automated-3D ultrasound). Main results and the role of chance The median number of follicles ≥11mm counted via automated-3D [ 10 (IQR: 5.75 – 16)] and the median number of follicles ≥11mm found via manual-2D assessment [10 (IQR: 6.75 – 18)] was similar between the two groups. Τhe median number of oocytes retrieved was 12 (IQR: 6.75 – 18). A high correlation of R = 0.915 was observed between the number of follicles found to be ≥ 11mm via automated-3D and 2D. However, regarding the number of oocytes collected, the predictive ability of automated-3D, was found to be, significantly higher (R2=0.837) than the predictive ability of 2d-ultrasound (R2=0.734) when all follicles ≥11mm were taken into account. These findings suggest that while the number of follicles measured to be ≥ 11mm was similar in both methods, automated 3D-ultrasound measurement offers a higher ability to predict the number of oocytes retrieved, compared to manual 2D-ultrasound measurements. Limitations, reasons for caution The present study compared manual 2D and automated 3D-ultrasound follicle measurements in the general IVF population. Future studies using a larger patient population will be useful to determine any potential differences between the two methods in patients stratified according to ovarian response. Wider implications of the findings Manual 2D and automated 3D-ultrasound assessment provide similar measurements of follicle number and size in patients undergoing IVF but automated-3D measurements offer greater predictive value regarding the number of oocytes collected and can be used effectively to monitor follicular development during ovarian stimulation for IVF. Trial registration number N/A

Does adjuvant letrozole reduce uterine peristalsis prior to fresh embryo transfer?

STUDY QUESTIONDoes adjuvant letrozole in ovarian stimulation for IVF decrease the uterine peristalsis frequency (UPF) prior to fresh embryo transfer (ET)?SUMMARY ANSWERAdjuvant letrozole in ovarian stimulation for IVF does not reduce the UPF significantly prior to fresh ET.WHAT IS KNOWN ALREADYThroughout the cycle, uterine peristalsis aids spermatozoa transport to the fallopian tube and may affect implantation. At fresh ET, UPF is negatively correlated with implantation and clinical pregnancy rates and is believed to be modulated by oestradiol and progesterone. High levels of oestradiol, from multiple follicular development, in ovarian stimulation have been reported to increase UPF, whereas progesterone is considered to be an utero-relaxant. The influence of androgens is unclear. Co-treatment with letrozole during gonadotropin ovarian stimulation limits the supra-physiological oestradiol rise and may therefore reduce UPF prior to fresh ET.STUDY DESIGN, SIZE, DURATIONThis study was carried out on subjects participating in a single-centre double-blinded randomized controlled trial of the impact of letrozole on follicle development and endocrine profiles, and investigated the impact of adjuvant letrozole in ovarian stimulation for IVF on UPF prior to fresh ET and the correlations of UPF with endocrine markers. Between 2016 and 2017, 39 women expected to be normal responders were randomized to co-treatment with letrozole or placebo. Of these, 33 women completed this element of the study. The study was carried out according to the Helsinki Declaration and the ICH-Good-Clinical-Practice.PARTICIPANTS/MATERIALS, SETTING, METHODSEligible women were randomized 1:1 to adjuvant treatment with letrozole 5 mg/day or placebo in an antagonist protocol using a fixed dose of recombinant (r) FSH 150 IU/day. Final maturation was triggered with hCG 6500 IU and luteal support with vaginal progesterone was administered from the day following oocyte aspiration. Less than 1 h prior to fresh ET, 6-min duration transvaginal ultrasound recordings of the uterus in sagittal section were performed and blood samples were drawn.MAIN RESULTS AND THE ROLE OF CHANCEA total of 33 women completed the study (letrozole n = 17; placebo n = 16). Age, BMI and ovarian reserve markers were similar between the groups. On the day of ET, serum oestradiol levels were significantly suppressed in the letrozole group to a mean of 867 ± 827 pmol/l compared to 3110 ± 1528 pmol/l in the placebo group (P < 0.001). Mean UPF prior to fresh ET did not differ between the intervention and placebo group (3.3 ± 0.36 versus 3.5 ± 0.51 per minute respectively, P = 0.108). UPF was assessed and agreed by two observers who were blinded to adjuvant treatment. Two patients were excluded due to poor quality of the ultrasound recordings. Supra-physiological serum oestradiol in the placebo group were negatively correlated with UPF (P = 0.014; R = –0.62), but the more physiological serum oestradiol levels in the letrozole group showed no correlation with UPF (P = 0.567; R = 0.15). Serum progesterone levels were similar in both groups and did not show any significant correlation with UPF. Testosterone levels were significantly higher in the letrozole group (P = 0.005) and showed a non-significant trend that negatively correlated with UPF in the placebo group (P-value = 0.071, R = –0.48).LIMITATIONS, REASONS FOR CAUTIONLimitations of the study included the limited sample size and the lack of a power calculation specifically determined for this endpoint.WIDER IMPLICATIONS OF THE FINDINGSThe supra-physiological levels of oestradiol generated during ovarian stimulation were significantly suppressed in the intervention group. However, UPF prior to fresh ET was similar in both groups. Modulating the luteal phase sex steroids with adjuvant letrozole had little measured impact on UPF. Any beneficial effect of adjuvant letrozole during ovarian stimulation is unlikely to be due to significant modulation of UPF.STUDY FUNDING/COMPETING INTEREST(S)M.D.H.’s salary was funded by an unrestricted research grant from Gedeon Richter. The expenses of the study were funded by a scientific collaboration: ReproUnion, co-financed by the European Union, Interreg Öresund-Kattegat-Skagerrak and Ferring Pharmaceuticals. The assays for the analyses were funded by Roche Diagnostics and an unrestricted research grant from Merck Life Science AS, Denmark. The authors have no competing interests to declare regarding this study.TRIAL REGISTRATION NUMBERClinicaltrials.gov: NCT02939898, EudraCT no.: 2015-005683-41.

Uterine Cavity Irrigation With Office Hysteroscopy During Ovarian Stimulation for IVF: A Randomized Controlled Trial.

ObjectiveThis was a non-blinded randomized controlled study to evaluate whether endometrial irrigation via office hysteroscopy during the early follicular phase would lead to a higher level of live birth rates compared to no irrigation in the fresh embryo transfer cycle.MethodThe study was conducted in Tehran university of medical sciences from June 2015 to June 2016. women under the age of 40 with primary infertility without history of previous IVF/ICSI or hysteroscopic examination, were included. Controlled ovarian hyperstimulation was done. Hysteroscopy was performed in the early mid-follicular phase of a stimulation cycle (day 5-7) with a vaginoscopy approach and saline irrigation in hysteroscopy group. Embryo-transfer was done in the same cycle.Results228 patients completed their participation in the study. In the fresh cycle, clinical pregnancy rate was 46% in the hysteroscopy group and 40.43% in the control group. (p-value= 0.326, RR= 1.16 [95%CI: 0.862 to 1.56]). Live birth rate was 41.28% in the hysteroscopic group and 31.93% in the control group (p-value=0.143, RR= 1.293 [95%CI: 0.916 to 1.825]). For those patients having surplus cryopreserved embryos, after 2 months, a second embryo transfer was performed. The cumulative LBR was 44.05% in the hysteroscopic group and 32.25% in the control group (p-value=0.029, RR= 1.368 [95%CI: 1.031 to 1.815], RD= 11.9% [95%CI: 1.2% to 22.3%] and NNT= 8 [95%CI: 4 to 85]).ConclusionThe current study clearly demonstrated a significantly higher cumulative live birth rate in the intervention group.Clinical Trial Registration[https://www.irct.ir/trial/19586], identifier IRCT2016011022795N2.

P–636 Anti-Müllerian-Hormone levels are not correlated to the probability of obtaining an ongoing pregnancy and time to pregnancy in women undergoing intra-uterine inseminations with donor sperm

Abstract Study question Is Anti-Müllerian hormone (AMH) level associated with the probability of obtaining an ongoing pregnancy (OP) and with time to pregnancy (TTP) in women undergoing d-IUI? Summary answer AMH is neither associated with the probability of obtaining an OP nor with time to pregnancy (TTP) in women undergoing d-IUI What is known already Anti-Müllerian hormone (AMH) is a glycoprotein produced by the granulosa cells of preantral and antral follicles. While AMH has been widely recognized as a quantitative marker of ovarian reserve used to predict ovarian responsiveness to ovarian stimulation in IVF, its relationship with fecundability in spontaneous conceptions is still a matter of debate. There is currently no consensus on the role of AMH on time to pregnancy in unassisted conceptions. The question of whether AMH is a qualitative marker of oocyte quality is therefore still unanswered. Study design, size, duration This prospective cohort study was carried out between 9/1/2017 and 12/30/2020 on 592 women aged 19 to 44, who underwent d-IUI in a natural cycle (n = 1788) the day after LH peak. Patients were single, homosexual, or heterosexual with an infertile partner and underwent 1 to maximum 6 d-IUI. All patients had regular ovulatory cycles and bilateral tubal patency confirmed before starting d-IUI. AMH evaluation was performed within the previous 3 months of the first d-IUI. Participants/materials, setting, methods The primary outcomes were the likelihood of obtaining an OP (&amp;gt;14 weeks) and TTP calculated as the number of d-IIU up to an OP. Multivariate logistic regression was used to compare the probability of obtaining an OP according to age and AMH levels. Kaplan-Meier curves with log-rank test were used to assess the TTP stratified by age groups (≤35, &amp;gt;35 to ≤ 39, and &amp;gt; 39 years old) and AMH groups (&amp;lt; 1ng/mL and ≥ 1ng/mL). Main results and the role of chance AMH levels were negatively correlated with age (p &amp;lt; 0.001). OP were significantly lower with increasing age (OR 0.92 (0.89–0.95) p &amp;lt; 0.001) but did not differ according to AMH levels (OR 1.07 (0.97–1.18) p = 0.18). When adjusting for AMH, the association between age and OP remained significant (OR 0.91 (0.88–0.95)). TTP was significantly different between age groups: ≤35 years old (n = 338), &amp;gt;35 to ≤ 39 years old (n = 136) and &amp;gt; 39 years old (n = 118) (p &amp;lt; 0.001), but did not differ significantly according to AMH levels &amp;lt; 1ng/mL (n = 130) and ≥1ng/mL (n = 462)(p = 0.55). Limitations, reasons for caution Our results concern d-IUI and can therefore not be extrapolated to natural conception. However, the study model is close to natural fecundity as there was no history of female infertility and as all IUI were performed on the day of ovulation with donor sperm proven to be fertile. Wider implications of the findings: While measuring AMH seems necessary for gonadotropin dose adjustment in ART, our data suggest that it cannot qualitatively assess fertility outcome and should therefore not be used routinely for preconception counseling in the absence of infertility history. Trial registration number P2017/396

P–723 Ovarian reserve parameters and ovarian stimulation outcome for IVF/ICSI are influenced by ethnicity

Abstract Study question Are the ovarian reserve parameters and the outcome of ovarian stimulation for IVF / ICSI influenced by ethnicity? Summary answer Ethnicity influences ovarian reserve parameters and the outcome of ovarian stimulation for IVF / ICSI What is known already Infertility affects couples worldwide and due to a lack of a standardized reporting system, the real number, especially in developing countries, might be underestimated. The etiology of infertility may differ around the world and is often subjected not only to social, cultural and religious peculiarities, but also to different genetic influences. Published data suggest that ethnicity influences the ovarian reserve as well as the outcome of Assisted-Reproductive-Techniques (ART)-treatments. Key players of a successful ART outcome are the ovarian reserve and consequently the number of oocytes retrieved. Until today, the impact of ethnical differences is not sufficiently addressed in research. Study design, size, duration Prospective observational study, performed in 10 infertility centers worldwide (Europe (4 centers), Middle East North Africa (MENA) region (2 centers), Iran (2 centers), South America (1 center), India (1 center)) between May 2019 and September 2020, evaluating ovarian reserve and outcome parameters of ovarian stimulation treatments for IVF/ICSI. The study was approved by the Ethical Committee of each participating center. Participants/materials, setting, methods Couples with primary / secondary infertility and an indication for an IVF/ICSI treatment were included into this study. Besides anamnestic data regarding the history of the infertility and self-reported ethnicity (Arab, Caucasian, Hispanic, Ohters, Persian and South Asian), data obtained during the basic fertility assessment on the ovarian reserve parameters (Antral follicle count (AFC) and Anti-Muellerian-Hormone (AMH)) as well as stimulation parameters from the ovarian stimulation treatment were collected and analyzed. Main results and the role of chance This study comprised 1032 couples with the following distribution of the ethnicities: Arab 21.5%, Caucasian 15.9%, Hispanic 5%, Others 1.2%, Persian 33.4%, and South Asian 23%. The unadjusted means, SD and 95%CI (Confidence Interval) of AMH (ng/ml) for the groups were 3.33±0.19 [2.95–3.71]; 2.03±0.25 [1.55–2.52]; 2.43±0.74 [0.97–3.88]; 2.76±0.96 [0.88–4.64]; 3.10±0.16 [2.79–3.41]; 3.62±0.19 [3.25–3.98], for AFC 15.52±0.53 [14.49–16.55]; 12.00±0.67 [10.69–13.31]; 12.69±1.08 [10.57–14.81]; 15.11±2.60 [10.01–20.21]; 13.58±0.42 [12.75–14.41]; 13.49±0.51 [12.49–14.48] and for the number of retrieved oocytes (rCOC) 14.08±0.61 [12.88–15.27]; 9.84±0.71 [8.44–11.24]; 7.94±1.26 [5.48–10.41]; 9.92±2.62 [4.78–15.05]; 10.83±0.49 [9.87–11.79]; 17.06±0.59 [15.90–18.21], respectively. Univariate analysis of AMH, AFC and rCOC with the ethnicities revealed highly statistically significant differences for AMH and rCOC (p &amp;lt; 0.001, respectively) and significant differences for AFC (p = 0.0014). As age is a major confounder for the ovarian reserve, multivariate analyses were performed. After adjusting for age, AMH was significantly different between Arab-Persian, Arab-South Asian and Arab-Caucasian (p &amp;lt; 0.001, p &amp;lt; 0.001, p = 0.002) and AFC statistically significant between Arab and all other ethnicities. For rCOC, besides age, also the stimulation-dosage and -duration was taken into account. Highly statistically significant differences were found for the groups Arab-Persian and Arab-Caucasian and no differences towards the other ethnical groups. Limitations, reasons for caution Limitations of the study are an unequal number of included patients per ethnicity and that the data for the ovarian reserve parameters and the stimulation outcome were not available for all of the included patients. Wider implications of the findings: Counselling of couples with infertility have to take, besides all other factors, also the ethnicity of the couple into account as ethnicity influences the ovarian reserve parameters as well as the number of retrieved oocytes in ovarian stimulation cycles for IVF/ICSI. Trial registration number ClinicalTrials.gov Identifier: NCT03927417

P-643 Pre-selected for an award: Is Euploid blastocyst number higher in luteal versus follicular phase? A case-control study of IVF outcomes of follicular versus luteal phase ovarian stimulation

Abstract Study question Is there a difference between IVF outcomes in patients undergoing follicular versus luteal phase ovarian stimulation in different menstrual cycles? Summary answer Number of euploid blastocyst were higher in luteal phase ovarian stimulation IVF cycles. All other outcomes were similar between follicular and luteal phase IVF cycles. What is known already It has been published that human beings can have two or three follicular recruitment waves as observed in animals studies a long time ago. From these findings, several recent studies showed that two egg retrievals at the same menstrual cycle, named as Duo Stim, optimize time and IVF outcomes in women with low ovarian reserve due to more eggs retrieved in a shorter period with consequently higher probability of having good embryos to transfer. However, there is no knowledge about diferences concerning IVF outcomes between folicular and luteal ovarian stimulation, performed at the same women in different menstrual cycles. Study design, size, duration Retrospective, case-control study in a single IVF center. One-hundred-two patients who had two IVF treatments – the first cycle initiating ovarian stimulation at follicular phase (FPS) and the second cycle initiating after a spontaneous ovulation at luteal phase (LPS) – in different menstrual cycles (until 6 months apart) between 2014 and 2020, were included. Statistical analysis was performed with Mann-Whitney test and was considered significant when p ≤ 0.05. Data is represented as mean±SD. Participants/materials, setting, methods Patients underwent two IVF treatments in different menstrual cycles; the FPS IVF treatment was initiating at D2/D3 of menstrual cycle and the LPS treatment started three or four days after spontaneous ovulation, if at least 4 antral follicles were detected. Both IVF treatments were performed with and antagonist protocol and freeze all strategy. The majority of patients presents low ovarian reserve/Ovarian age as primary infertility factor (84.3%). Main results and the role of chance Patient’s mean age was 39.30±3.15 years, BMI (22.66±3.16) and AMH levels (0.85±0.85 ng/mL). Comparison of hormonal levels at the beginning of ovarian stimulation showed differences for FPS vs LPS, as expected: E2 (39.69±31,10 pg/mL vs 177.33±214.26 pg/mL, p &amp;lt; 0.0001) and P4 (0.76±2.47ng/mL vs 3,00±5.00 ng/mL,p &amp;lt; 0.0001). However, E2 and P4 at the day of oocyte maturation trigger were not different between FPS and LPS (1355.24±895.73 pg/mL vs 1133.14±973.01 ng/mL,p = 0.0883 and 1.12±1.49 ng/mL vs 2.94±6.51,p = 0.0972 respectively). There was no difference for total dose of gonadotrofins (FPS 2786.43±1102.39.01UI vs LPS 2824.12±1188.87UI, p = 0,8578), FSH (FPS 9.50±4.98 vs LPS 11.90±12.99, p = 0.7502) and AFC (FPS 7.13±4.25 vs LPS 6.42±4.65,p = 0,0944). From 102 patients that started ovarian stimulation, 78 had 1 or more oocyte collect in FPS group and 75 in LPS group: OPU (FPS 4.78±4.93 vs LPS 4.65±5.54,p = 0.7889), number of MII (FPS 3.21±3.52 vs LPS 3.40±4.53,p = 0.7889). From those, 52 patients performed ICSI in both cycles; fertilization rate 64.9%±28.6% for FPS vs 62.1%±32.4% for LPS,p = 0.7899) and blastocyst formation 2.15±2.15 for FPS vs 2.54±2.35,p = 0.3496). Data from 25 patients who had embryo biopsy for PGT-A showed similar number of blastocyst biopsed (2.12±1.72 FPS vs 2.48±1.71 LPS,p = 0.3101) and a statistically significant difference regarding number of euploid blastocyst (0,20±0,41 FPS vs 0,96±0,93 LPS,p = 0,0008). Limitations, reasons for caution This is a retrospective study in a limited number of patients. Therefore, it is not possible to make a definitive conclusion that LPS proportionate higher number of euploid than FPS. More studies are necessary to investigate not only IVF outcomes but also the impact on pregnancy rates. Wider implications of the findings In our study, LPS protocol after spontaneous ovulation, presents similar IVF outcomes compared to routinely FPS protocol. Intriguingly, the number of euploid blastocyst was significant higher in LPS, which may be further investigated. In this way, LPS is another option of IVF treatment, and may optimize time and treatment results. Trial registration number Not Applicable

P–643 Is Euploid blastocyst number higher in luteal versus follicular phase? A case-control study of IVF outcomes of follicular versus luteal phase ovarian stimulation

Abstract Study question Is there a difference between IVF outcomes in patients undergoing follicular versus luteal phase ovarian stimulation in different menstrual cycles? Summary answer Number of euploid blastocyst were higher in luteal phase ovarian stimulation IVF cycles. All other outcomes were similar between follicular and luteal phase IVF cycles. What is known already It has been published that human beings can have two or three follicular recruitment waves as observed in animals studies a long time ago. From these findings, several recent studies showed that two egg retrievals at the same menstrual cycle, named as Duo Stim, optimize time and IVF outcomes in women with low ovarian reserve due to more eggs retrieved in a shorter period with consequently higher probability of having good embryos to transfer. However, there is no knowledge about diferences concerning IVF outcomes between folicular and luteal ovarian stimulation, performed at the same women in different menstrual cycles. Study design, size, duration Retrospective, case-control study in a single IVF center. One-hundred-two patients who had two IVF treatments – the first cycle initiating ovarian stimulation at follicular phase (FPS) and the second cycle initiating after a spontaneous ovulation at luteal phase (LPS) – in different menstrual cycles (until 6 months apart) between 2014 and 2020, were included. Statistical analysis was performed with Mann-Whitney test and was considered significant when p ≤ 0.05. Data is represented as mean±SD. Participants/materials, setting, methods Patients underwent two IVF treatments in different menstrual cycles; the FPS IVF treatment was initiating at D2/D3 of menstrual cycle and the LPS treatment started three or four days after spontaneous ovulation, if at least 4 antral follicles were detected. Both IVF treatments were performed with and antagonist protocol and freeze all strategy. The majority of patients presents low ovarian reserve/Ovarian age as primary infertility factor (84.3%). Main results and the role of chance Patient’s mean age was 39.30±3.15 years, BMI (22.66±3.16) and AMH levels (0.85±0.85 ng/mL). Comparison of hormonal levels at the beginning of ovarian stimulation showed differences for FPS vs LPS, as expected: E2 (39.69±31,10 pg/mL vs 177.33±214.26 pg/mL,p&amp;lt; 0.0001) and P4 (0.76±2.47ng/mL vs 3,00±5.00 ng/mL,p&amp;lt; 0.0001). However, E2 and P4 at the day of oocyte maturation trigger were not different between FPS and LPS (1355.24±895.73 pg/mL vs 1133.14±973.01 ng/mL,p=0.0883 and 1.12±1.49 ng/mL vs 2.94±6.51,p=0.0972 respectively). There was no difference for total dose of gonadotrofins (FPS 2786.43±1102.39.01UI vs LPS 2824.12±1188.87UI, p = 0,8578), FSH (FPS 9.50±4.98 vs LPS 11.90±12.99,p=0.7502) and AFC (FPS 7.13±4.25 vs LPS 6.42±4.65,p=0,0944). From 102 patients that started ovarian stimulation, 78 had 1 or more oocyte collect in FPS group and 75 in LPS group: OPU (FPS 4.78±4.93 vs LPS 4.65±5.54,p=0.7889), number of MII (FPS 3.21±3.52 vs LPS 3.40±4.53,p=0.7889). From those, 52 patients performed ICSI in both cycles; fertilization rate 64.9%±28.6% for FPS vs 62.1%±32.4% for LPS,p=0.7899) and blastocyst formation 2.15±2.15 for FPS vs 2.54±2.35,p=0.3496). Data from 25 patients who had embryo biopsy for PGT-A showed similar number of blastocyst biopsed (2.12±1.72 FPS vs 2.48±1.71 LPS,p=0.3101) and a statistically significant difference regarding number of euploid blastocyst (0,20±0,41 FPS vs 0,96±0,93 LPS,p=0,0008). Limitations, reasons for caution This is a retrospective study in a limited number of patients. Therefore, it is not possible to make a definitive conclusion that LPS proportionate higher number of euploid than FPS. More studies are necessary to investigate not only IVF outcomes but also the impact on pregnancy rates. Wider implications of the findings: In our study, LPS protocol after spontaneous ovulation, presents similar IVF outcomes compared to routinely FPS protocol. Intriguingly, the number of euploid blastocyst was significant higher in LPS, which may be further investigated. In this way, LPS is another option of IVF treatment, and may optimize time and treatment results. Trial registration number Not applicable

“One Size does not Fit All” during Ovarian Stimulation for IVF

“One Size does not Fit All” during Ovarian Stimulation for IVF

Cumulus cell microRNA expression when LH is added to the ovarian stimulation protocol: a pilot study

Research questionRecombinant FSH administration in ovarian stimulation for IVF is a standard procedure, whereas the role of LH is controversial. MicroRNAs (mRNA) are small endogenous non-coding transcripts that are involved in the regulation of many cellular processes, including foliculogenesis and gonadotrophin function. The aim was to study the possible role of miRNA in ovarian follicular development in groups having different ovarian stimulation protocols. Are there different miRNA expression profiles in cumulus cells of infertile women undergoing IVF? What are the regulated pathways? DesignThis prospective observational study included 13 patients who fulfilled the following inclusion criteria: younger than 38 years of age; a tubal infertility factor; a male factor; or idiopathic infertility. This is a pilot study in which the patients were aleatory enrolled into two groups: seven in FSH group (recombinant FSH, 225 IU) and six in FSH plus LH group (recombinant FSH, 150 IU + recombinant LH, 75 IU). The granulosa cells obtained from the follicular ovarian retrieval were analysed using polyerase chain reaction. Results were analysed using DIANA Tools, an online bioinformatics tool. ResultsAmong the 84 microRNAs evaluated, 11 were differentially expressed between the groups, all of which were upregulated in the FSH plus LH group, compared with the FSH group. Differentially expressed miRNA profiles are related to oestrogen signalling, oocyte meiosis and pluripotent cells regulation. ConclusionmiRNA overexpression in the FSH plus LH group is consistent with the independent and fundamental role of LH in folliculogenesis, leading to a distinct molecular response between groups.

What are the effects of estradiol as adjunct to transvaginal ultrasound (TVUS) for monitoring ovarian stimulation in IVF and ICSI?

What are the effects of estradiol as adjunct to transvaginal ultrasound (TVUS) for monitoring ovarian stimulation in IVF and ICSI?

Dydrogesterone versus medroxyprogesterone acetate co-treatment ovarian stimulation for IVF: a matched cohort study of 236 freeze-all-IVF cycles

This matched cohort study was retrospectively performed, with cycles extracted from freeze-all-IVF treatments performed between March and November 2019, to compare the efficacy of flexible-start dydrogesterone (DYG) co-treatment ovarian stimulations (OS) with flexible-start medroxyprogesterone acetate (MPA) co-treatment OS. DYG cycles were matched 1:1 with MPA cycles using female age and antral follicle count, resulting in 236 matched cycles. OS durations and total FSH doses were similar in DYG and MPA OS cycles. The numbers of mature oocytes retrieved were similar; however, the mature oocyte retrieval rate was significantly lower (66.7 vs. 78.2%; p = .001) and the cycle cancellation rates were higher (29.2 vs. 21.2%; p = .056) in DYG co-treatments. A linear regression selected OS co-treatment protocol (0.53 DYG (0.356–0.776), p = .001) into the final model to predict a ≥ 80% mature oocyte retrieval rate. The per transfer (47.2 vs. 49.7; p = .721) and per treatment ongoing pregnancy rates (32.2 vs. 38.1%, p = .210) were similar in the two co-treatment groups. Flexible-start DYG co-treatment OS was as effective in blastocyst freeze-all-IVF cycles as MPA co-treatment, with similar ongoing pregnancy rates; however, mature oocyte retrieval was significantly decreased and cycle cancellation increased in DYG cycles. Impact statement What is already known on this subject? Progestin (i.e. artificial progesterone) co-treatment has long been known to be a feasible alternative to conventional GnRH-analogue co-treatment in OS for IVF, because of the long-standing evidence that progestin formulations have in oral contraceptive therapies. The recent evolution of effective freeze-all-IVF (in which high mid-cycle progesterone levels is not of concern because of the postponement of embryo transfer) has now made it possible to investigate progestin co-treatment OS in IVF. What do the results of this study add? Ongoing pregnancy rates from blastocyst frozen embryo transfers in flexible-start dydrogesterone (DYG) co-treatment ovarian stimulation (OS) cycles were similar to rates in flexible-start medroxyprogesterone acetate (MPA) co-treatment OS cycles. The mature oocyte retrieval rate was significantly lower and the cycle cancellation rate higher in DYG than in MPA cycles. What are the implications of these findings for clinical practice and/or further research? The evidence suggests that MPA co-treatment should be preferred in OS for IVF. Further investigation is required to refine progestin co-treatment protocols, because of their potential to reduce the number of viable blastocysts.

Suboptimal response to controlled ovarian stimulation in IVF / ICSI cycles

Hypothesis/Aims of study. Currently, the frequency of suboptimal response (4-9 retrieved oocytes) to controlled ovarian stimulation (COS) in woman is quite high; however, its efficacy is poorly studied. The aim of this study was to evaluate the main characteristics of IVF / ICSI programs in patients with a suboptimal response to COS.&#x0D; Study design, materials and methods. We performed a retrospective study of 412 IVF / ICSI cycles in women with a suboptimal response to COS, including a comparative analysis of clinical and embryological parameters, ovarian reserve and the efficacy of IVF / ICSI protocols.&#x0D; Results. Clinical pregnancy rate in ovarian stimulation cycles with a suboptimal response to COS was 27.9%. The efficacy of assisted reproductive technology (ART) programs in women with uterine fibroids was significantly lower than in patients without fibroids (19.1% vs. 30.5%, p = 0.03; OR = 0.54; 95% CI: 0.31-0.95). Clinical pregnancy rate in patients with male factor infertility was significantly higher than in women with anovulation (37.1% vs. 20.9%, р = 0.005; OR = 2.24; 95% CI: 1.27-3.94) or tubal factor infertility (37.1% vs. 24.8%, р = 0.02; OR = 1.79; 95% CI: 1.09-2.94). There were significant correlations between the number of retrieved oocytes with serum anti-Mllerian hormone (AMH) concentration (r = 0.32, p 0.001) and antral follicle count (AFC) (r = 0.38, p 0.001). In addition, the need for follicle-stimulating hormone (FSH) preparations during COS correlated significantly with ovarian reserve parameters (AMH and AFC) (r = 0.45 and 0.44, both p 0.001, respectively) and the age of patients (r = 0.47; p 0.001).&#x0D; Conclusion. The clinical pregnancy rate in women with a suboptimal response to COS was low. Concomitant uterine fibroids represented an additional factor of negative influence on IVF / ICSI outcomes in women with a suboptimal response to COS. The male factor of infertility in patients with a suboptimal response did not reduce the efficacy of ART programs. Ovarian reserve parameters in women with a suboptimal response correlated with the need for FSH preparations during COS and the number of retrieved oocytes.

A form of secondary ovarian insufficiency (SOI) due to adrenal hypoandrogenism as new infertility diagnosis.

Mediated via the androgen receptor on granulosa cells, models of small growing follicle stages demonstrate dependence on testosterone. Androgen deficiency reduces ovarian response to follicle stimulation hormone (FSH), granulosa cell mass and estradiol (E2) production falls and FSH, therefore, rises. Though potentially of adrenal and/or ovarian origin, androgen deficiency in association with female infertility is almost universally primarily of adrenal origin, raising the possibility that women with presumptive diagnosis of primary ovarian insufficiency (POI), also called primary ovarian failure (POF) may actually suffer from secondary ovarian insufficiency (SOI) due to adrenal hypoandrogenism that leads to follicular arrest at small-growing follicle stages. This retrospective cohort study was performed in a private, academically affiliated infertility center in New York City. We searched the center's anonymized electronic research data bank for consecutive patients who presented with a diagnosis of POI, defined by age <41 year, FSH > 40.0 mIU/mL, amenorrhea for at least 6 month, and low testosterone (T), defined as total T (TT) in the lowest age-specific quartile of normal range. This study did not include patients with oophoritis. Since dehydroepiandrosterone sulfate (DHEAS) is the only androgen almost exclusively produce by adrenals, adrenal hypoandrogenism was defined by DHEAS < 100ug/dL. Thirteen of 78 presumed POI women (16.67%) qualified and represented the original study population. POI patients are usually treated with third-party egg donation; 6/13, however, rejected egg donation for personal or religious reasons and insisted on undergoing at least one last IVF cycle attempt (final study population). In preparation, they were supplemented with DHEA 25 mg TID and CoQ10 333 mg TID for at least 6 weeks prior to ovarian stimulation for IVF with FSH and human menopausal gonadotropins (hMG). Since POI patients are expected to be resistant to ovarian stimulation, primary outcome for the study was ovarian response, while secondary outcome was pregnancy/delivery. Though POI/POF patients usually are completely unresponsive to ovarian stimulation, to our surprise, 5/6 (83.3%) patients demonstrated an objective follicle response. In addition, 2/6 (33.3%) conceived spontaneously between IVF cycles, while on DHEA and CoQ10 supplementation and delivered healthy offspring. One of those is currently in treatment for a second child. This preliminary report suggests that a surprising portion of young women below age 41, tagged with a diagnosis of POI/POF, due to adrenal hypoandrogenism actually suffer from a form of SOI, at least in some cases amenable to treatment by androgen supplementation. Since true POI/POF usually requires third-party egg donation, correct differentiation between POI and SOI in such women appears of great importance and may warrant a trial stimulation after androgen pre-supplementation for at least 6 weeks.