Controlled Ovarian Hyperstimulation Cycles Research Articles

P-359 Ten years’ experience using cryopreserved oocytes from In Vitro Maturation (IVM) or Controlled Ovarian Hyperstimulation (COH) cycles for fertility preservation in oncologic indications

Abstract Study question Is IVM a relevant option for fertility preservation in cancer patients, considering biological/clinical outcomes post-thawing, compared to COH? Summary answer This study shows that despite a significantly altered embryo morphology within the IVM group, the clinical outcomes remain comparable to those of COH. What is known already Fertility Preservation (FP) techniques are proposed to patients with cancer to provide the possibility of childbearing using their own gametes. Currently, oocyte vitrification after COH is the standard option. IVM serves as an alternative when COH is contraindicated, urgent cancer therapy is required, or in conjunction with ovarian cortex cryopreservation. Limited live births have been reported from frozen-thawed oocytes in IVM cycles of cancer survivors. Scarce data are available for comparing biological/clinical outcomes of frozen-thawed oocytes from IVM versus COH cycles in cancer survivors. Study design, size, duration This bicentric retrospective cohort study aimed to analyze the outcomes of all oocyte warming cycles in 73 cancer survivors having undergone oocyte vitrification for FP after COH and/or IVM. All of them had oocyte retrieval before the administration of gonadotoxic treatment and returned after being cured, with their oncologist agreement, for assisted reproduction treatments, between November 2012 and January 2024. Participants/materials, setting, methods Seventy-seven warming attempts followed by ICSI respectively from 37 COH and 40 IVM cycles were analyzed. Four patients benefited from an IVM and COH cycle. Survival, fertilization, top and good-quality embryos, defined at day-2 respectively as 4 and 3-5 adequate-sized blastomeres, without multinucleation with < 20% of cytoplasmic fragments, implantation, biochemical (hCG>100 UI/mL), clinical (intrauterine sac with fetal heartbeat) and live birth rates were compared using appropriate statistical tests. Main results and the role of chance The mean age and antral follicle count at the time of FP was similar in both groups. The indications for FP were breast cancer (n = 61), hematologic malignancies (n = 7), ovarian cancer (n = 3), other (n = 2). The number of cryopreserved oocytes tended to be higher in the COH group, when compared to the IVM group (8.5±7.3 vs 5.9±4.04; p = 0.16). The mean oocyte maturation rate after IVM was 68.6±23.1%. Oocyte survival, and fertilization rates were similar in COH and IVM groups, respectively (76.4±27.0% vs 76.1±22.0%; p = 0.76) and (67.1±34.3% vs 65.3±25.4%; p = 0.36). We reported a significantly better embryo quality at day-2 in the COH group when compared to the IVM group, with respectively top-quality embryos (44.0±34.2% vs 26.1±33.4%, p = 0,04) and good-quality embryos (62.2±38.0% vs 42.8±40.8%, p = 0.049), and also a significantly higher number of useful embryo in the COH group (2.7±2.6 vs 1.5±1.2, p = 0.03). Regarding clinical outcomes, the results were similar in COH and IVM groups, in terms of implantation rates (12.2±30.4% vs 15.5±35.6%; p = 0.86), biochemical (32.3% (10/31) vs 17.9% (6/28); p = 0.39), clinical pregnancies (25.8% (8/31) vs 17.9% (4/28); p = 0.54), live birth rates ( 25.8% (8/31) vs 14.3% (4/28); p = 0.34). Limitations, reasons for caution Statistical power to compare IVF outcomes after COH and IVM is limited by the few women who returned to use their frozen oocytes. The subjective nature of embryo morphology assessment. Wider implications of the findings This study is the largest evaluating frozen-warmed oocytes from IVM cycles in cancer patients, with 5 live births newly reported. A higher oocyte-yield may be necessary in IVM as the number of useful embryos is significantly lower. Novel approaches are being developed to improve maturation rates following IVM. Trial registration number Not applicable

Reassessing the impact of letrozole co-administration in controlled ovarian hyperstimulation: findings from a single-center repeated measures study.

To explore whether letrozole improved outcomes in subsequent controlled ovarian hyperstimulation (COH) cycles. This was a retrospective repeated measures cohort study examining COH cycles. Patients were included if they underwent two cycles for unexplained infertility, male factor infertility, or planned oocyte/embryo cryopreservation. The first cycles for all patients implemented a non-letrozole, conventional gonadotropin protocol. Second cycles for the study group included letrozole (2.5-7.5 mg for 5 days) with no medication change to second cycles amongst controls. Our primary objective was to compare oocyte yield. Cohorts were then subdivided by pursuit of oocyte (OC) or embryo (IVF) cryopreservation. Secondary outcome amongst the OC subgroup was oocyte maturation index (metaphase II (MII)/total oocytes). Secondary outcomes amongst the IVF subgroup were normal fertilization rate (2-pronuclear zygotes (2PN)/oocytes exposed to sperm), blastocyst formation rate (blastocysts/2PNs), and embryo ploidy (%euploid and aneuploid). Fifty-four cycles (n = 27) were included in letrozole and 108 cycles (n = 54) were included in control. Oocyte yield was higher in second cycles (p < 0.008) in the letrozole group but similar in second cycles (p = 0.26) amongst controls. Addition of letrozole did not impact MII index (p = 0.90); however, MII index improved in second cycles amongst controls (p < 0.001). Both groups had similar rates of normal fertilization (letrozole: p = 0.52; control: p = 0.61), blast formation (letrozole: p = 0.61; control: p = 0.84), euploid (letrozole: p = 0.29; control: p = 0.47), and aneuploid embryos (letrozole: p = 0.17; control: p = 0.78) between cycles. Despite improved oocyte yield, letrozole did not yield any difference in oocyte maturation or embryo outcomes.

P-617 Combined oral contraceptive pill (COCP) pre-treatment and progestin-primed ovarian stimulation (PPOS) protocol: a detrimental combination for the oocyte yield in egg donation programs

Abstract Study question Could the use of combined oral contraceptive pill (COCP) pre-treatment before controlled ovarian hyperstimulation (COH) have a negative effect on oocyte yield in normo-responders patients? Summary answer When COH with progestin-primed ovarian stimulation (PPOS) protocol in normo-responders patients is performed, the COCP pre-treatment could have a detrimental effect on oocyte yield. What is known already COCP pre-treatment is widely used to schedule the start of COH and to organize the working week, but its usefulness and efficiency are still not clear. Most of studies on IVF outcomes have shown no effect of COCP on oocyte yield. For oocyte donation only few studies were carried out showing controversial effects on oocyte yield, but all considered short antagonist or long agonist protocols and no one PPOS protocol. COCP leads to long lasting pituitary suppression and lower LH level in follicular phase that could reduce the ability to effectively respond to GnRH-agonist trigger leading to poor oocyte yield. Study design, size, duration The egg donation cycles carried out from January to September 2022 in Next Fertility Valencia were retrospectively analyzed. Two analyses were conducted. Analysis A, comparative retrospective cohort study of 397 COH cycles: 290 with COCP and 107 without COCP. Analysis B, comparative retrospective paired study of 90 COH cycles: 45 with COCP and 45 without COCP, in which, to attempt to eliminate possible bias due to interpersonal differences, every patient was her own control. Participants/materials, setting, methods All donors underwent to COH with FSH monotherapy, PPOS protocol for pituitary suppression and a GnRH-agonist triggering. The oocyte yield was analyzed focusing on: the number of oocytes retrieved, mature (MII) oocytes and useful oocytes (good mature oocytes used for ICSI), the appropriate response to the GnRH-agonist trigger, the stimulation days, the total gonadotropins dose used and the cancellation rate (for low response or low LH level in follicular phase the first day of COH). Main results and the role of chance In both analyses, the data showed no differences in terms of stimulation days, total FSH dose, number of follicles ≥ 15 mm on the trigger day regardless of use of COCP. After conducting the analysis based on the administration or not of COCP, in the Analysis A a higher number of total oocytes retrieved, mature oocytes and useful oocytes were found in the group that did not used COCP. A significant difference in a nominal variable (Pearson's chi-square test) was observed, consisting of a higher proportion of cancellations due to low LH level (&amp;lt; 2,5 mUI/ml) in the group that used COCP (COCP no: 0.7% vs. COCP yes: 3.7% ). While, in the Analysis B (analysis of variance of one factor, Anova test), the variables total oocytes retrieved, total MII oocytes and total useful oocytes showed significant differences consisting of a higher number of oocytes in the group that did not received COCP. These results have statistical significance both before removing the cases in which the values were 0 due to a cancellation (p &amp;lt; 0.01), and after removing the cancelled cases (p &amp;lt; 0.05). Limitations, reasons for caution The main limitation lies in the retrospective nature of the study. However, since each patient is her own control (Paired study), it gives an added value. Wider implications of the findings COCP before COH in PPOS cycles could have detrimental effects on oocyte yield, reducing the efficacy and efficiency of egg donation programs. This could be extended to social freezing programs in normo-responders patients, in which the probability of future pregnancy is closely linked to the number of good oocytes vitrified. Trial registration number Not Applicable

Response to Ovarian Stimulation for Urgent Fertility Preservation before Gonadotoxic Treatment in BRCA-Pathogenic-Variant-Positive Breast Cancer Patients.

BRCA 1/2 pathogenic variants increase the risk of developing early and aggressive breast cancers (BC). For these patients, fertility potential can be directly affected by oncologic treatments. In addition, evidence indicates that BRCA-mutated women had a significant reduction in their ovarian reserve. In order to improve their chances of conception after the completion of cancer treatments, fertility preservation should be proposed before the administration of gonadotoxic drugs, ideally by oocyte vitrification after controlled ovarian hyperstimulation (COH). The present investigation aims to assess the ovarian response to COH in BRCA 1/2-pathogenic-variant carriers diagnosed with BC. Patient characteristics and COH outcomes were compared between BRCA-positive (n = 54) and BRCA-negative (n = 254) patients. The number of oocytes recovered did not differ between the two groups. However, the oocyte maturation rate and the number of mature oocytes obtained (7 (4.5-11.5) vs. 9 (5-14) oocytes, p = 0.05) were significantly lower in the BRCA-mutated patients. Although individualized COH protocols should be discussed, BRCA-mutated patients would benefit from FP before BC occurs, in order to cope with the potential accelerated decline of their ovarian reserve, optimize the success rate of FP by repeating COH cycles, and to preserve the feasibility of PGT-M by collecting a large amount of eggs.

The Effect of Human Growth Hormone on Endometrial Growth in Controlled Ovarian Hyperstimulation Cycles.

This study aims to compare endometrial growth before and after the addition of human growth hormone (hGH) in controlled ovarian hyperstimulation (COH) cycles. A 5-year retrospective cohort study of patients treated with hGH to improve oocyte development during COH cycles was conducted. Each patient's cycle without hGH immediately preceding cycle(s) with hGH was used for patients to serve as their own controls. Primary outcome was absolute growth in endometrial thickness from pre-stimulation start to day of hCG trigger. Mixed-model regression analysis controlled for patient correlation over repeat cycles and potential confounders. 80 patients were included. Mean age was 39.7 years; mean BMI was 23.8 kg/m2. Majority of patients were nulliparous, non-smoking, and White or Asian. Most common diagnosis was diminished ovarian reserve. Endometrial growth was compared between 159 COH cycles with hGH and 80 COH control cycles; mean increase was 4.5 mm and 3.9 mm, respectively-an unadjusted difference of 0.6 mm (95% CI: 0.2-1.1, p = 0.01). After adjusting for demographic/clinical factors, hGH was associated with 0.9 mm greater endometrial growth (0.4-1.4, p &lt; 0.01). Absolute increase in endometrial thickness was higher in COH cycles that included hGH. Further prospective studies in embryo transfer cycles are needed.

Serum Gonadotropin Levels Predict Post-Trigger Luteinizing Hormone Response in Antagonist Controlled Ovarian Hyperstimulation Cycles.

The objective of this study was to investigate the utility of using serum gonadotropin levels to predict optimal luteinizing hormone (LH) response to gonadotropin releasing hormone agonist (GnRHa) trigger. A retrospective cohort study was performed of all GnRH-antagonist controlled ovarian hyperstimulation (COH) cycles at an academic fertility center from 2017-2020. Cycles that utilized GnRHa alone or in combination with human chorionic gonadotropin (hCG) for trigger were included. Patient and cycle characteristics were collected from the electronic medical record. Optimal LH response was defined as a serum LH ≥ 40 mIU/mL on the morning after trigger. Total sample size was 3865 antagonist COH cycles, of which 91% had an optimal response to GnRHa trigger. Baseline FSH (B-FSH) and earliest in-cycle LH (EIC-LH) were significantly higher in those with optimal response. Multivariable logistic regression affirmed association of optimal response with EIC-LH, total gonadotropin dosage, age, BMI and Asian race. There was no difference in the number of oocytes retrieved (p = 0.14), maturity rate (p = 0.40) or fertilization rates (p = 0.49) based on LH response. There was no difference in LH response based on use of combination vs. GnRHa alone trigger (p = 0.21) or GnRHa trigger dose (p = 0.46). The EIC-LH was more predictive of LH trigger response than B-FSH (p < 0.005).The optimal B-FSH and EIC-LH values to yield an optimal LH response was ≥ 5.5 mIU/mL and ≥ 1.62 mIU/mL, respectively. In an era of personalized medicine, utilizing cycle and patient characteristics, such as early gonadotropin levels, may improve cycle outcomes and provide further individualized care.

DON’T BE TRIGGER SHY: A LOW SERUM LUTEINIZING HORMONE (LH) RESPONSE TO GONADOTROPIN-RELEASING HORMONE AGONIST (GnRH-A) HITS THE MARK IN PRE-IMPLANTATION GENETIC TESTING FOR ANEUPLOIDY (PGT-A)

The use of GnRH-a trigger in antagonist controlled ovarian hyperstimulation (COH) cycles has increased due to its enhanced safety profile. However, response, as measured by the serum LH level post trigger, vary considerably1-6. We investigated the impact of serum LH response to GnRH-a trigger in antagonist COH cycles on oocyte yield, oocyte maturity, blastocyst formation, PGT-A and pregnancy outcomes.

Accumulated Vitrified Embryos Could Be a Method for Increasing Pregnancy Rates in Patients with Poor Ovarian Response.

We aimed to assess the efficacy of accumulated embryo transfer (ACC-ET) through several controlled ovarian hyperstimulation (COS) cycles to increase the rates of pregnancy in patients with poor ovarian response (POR). We retrospectively reviewed the medical records of 588 patients with POR under 43-years old who underwent embryo transfer from January 2010 to December 2015. We compared the pregnancy rate (PR), clinical pregnancy rate (CPR), and live birth rate (LBR) between ACC-ET (frozen-thawed: 47; fresh + frozen-thawed: 24) group (n = 71) and fresh ET groups (n = 517). Characteristics of ACC-ET patients were similar to those of fresh ET groups (Age: 38.1 ± 3.5 vs. 38.2 ± 3.7, p = 0.88; Anti Müllerian Hormone (AMH; ng/mL): 0.5 ± 0.4 vs. 0.6 ± 0.6, p = 0.38; follicle stimulating hormone (FSH: mIU/mL): 11.9 ± 8.0 vs. 10.8 ± 9.0, p = 0.35). The total number of transferred embryos (3.1 ± 0.9 vs. 1.5 ± 0.7, p = 0.00), PR (29.6% (21/71) vs. 18.8% (97/517), p = 0.040), and CPR (23.5% (16/68) vs. 14.0% (71/508) p = 0.047) were significantly higher in the ACC-ET group than in the fresh ET group. In addition, PR, CPR, and LBR increased with the number of ET in the fresh ET group. However, there were no significant differences observed in LBR between ACC-ET and fresh ET groups (14.9% (10/67) vs. 9.8% (50/508), p = 0.203). From our knowledge, there is no clinical evidence reported to prove that transfer of multiple embryos of adequate quality obtained through multiple cycles can compensate for the limited number of retrieved oocytes from POR patients. We concluded that ACC-ET from several COS cycles could be an alternative method to increase PR and CPR in <43-year-old patients with POR.

P-553 Response to controlled ovarian stimulation and preimplantation genetic testing for molecular disease (PGT-M) outcomes for Myotonic dystrophy type I (DM1) : A French multicentric study

Abstract Study question Does ovarian response to controlled ovarian hyperstimulation (COH) is altered in female affected by DM1 ? Summary answer Ovarian response to COH is not altered in female affected by DM1 as compared to partners of affected males What is known already Myotonic dystrophy type 1 is the most common adult muscular dystrophy caused by a CTG trinucleotide repeat expansion which may expand across generation. As this pathology presents an autosomal dominant inheritance, PGT may be an option to achieve a pregnancy with healthy baby. There are conflicting reports about response to COH for affected female. Moreover, few data are available concerning the chance to have a healthy baby after PGT for couple with one member affected by DM1 Study design, size, duration The present study is a retrospective observational study carried out from January 2006 through January 2020. This multicentric study was conducted in all the five centers performing PGT-M in France. Participants/materials, setting, methods A total of 229 couples started at least one COH cycle for the PGT procedure. The patient carrying the mutation was the female for 178 couples and the male for the 51 others. Overall, 648 COH cycles started and 560 oocytes retrieval for subsequent PGT were performed (430 for affected female and 130 for affected male). Parameters of ovarian response and PGT outcomes were compared according to the member affected by DM1. Main results and the role of chance Age and BMI at the first COH cycle were not significantly different between both group but female carried mutation presented lower AMH level than partner of affected male. The starting and total doses of gonadotrophin were significantly higher for mutated females. The number of retrieved and mature oocytes per cycle were not statistically different (12 [8–16] versus 11 [8–16] retrieved oocytes, p = 0.63 and 9 [6–13] versus 9 [6-13] mature oocytes, p = 0.73, respectively). In both group, more than 70% of oocyte retrieval led to embryo biopsy. The proportion of started cycle allowing the obtention of at least one healthy embryo was significantly lower when the female was affected with DM1 (58.6% vs 70.4%, p = 0.012). In the female affected group, 49.7% of the cycles with oocytes retrieval lead to a fresh embryo transfer and a subsequent live birth rate per transfer of 21.4%. These results were not statistically different from the couple with affected male (58.5% of cycles with fresh embryo transfer (p = 0.08) and 23.6% live birth rate per transfer). Overall, after fresh or frozen embryo transfer, 30.8% of females with DM1and 41.2% of parter of affected males had at least one live birth from PGT. Limitations, reasons for caution This a retrospective study included patients who were selected ovarian reserve parameters before PGT process. Moreover, the large time of inclusion may influence our conclusion. Wider implications of the findings Information provided herein extends knowledge about the current state of COH for DM1 affected female. Moreover, PGT results presented here allow to provide patients with proposer counseling before starting PGT process. Trial registration number CEROG-2020-GYN-0603

Application of ultrasound markers measured at different time points of COH cycle in the prediction of ovarian response for individualised ovulation induction

The purpose of this study was to evaluate the predictive value of ultrasound markers measured at different time points of the controlled ovarian hyperstimulation (COH) cycle on ovarian response and outcome indicators in the IVF-ET cycle. According to the oestrogen level and the number of retrieved oocytes, patients who planned for COH treatment were separated into low-response group, normal and high-response group. The ovarian stromal artery flow parameters on the day of pituitary down-regulation, day 1, day 7, day 10, and the day of hCG injection were collected prospectively. We also have collected the data of cumulus oophorus count on the day of hCG injection by transvaginal sonography. Compared with the low-response group, on the first day of the COH cycle PI, RI, and S/D were lower in the high-response group than they were in the low-response group (p < .05). PSV and EDV were significantly higher in the high-response group than they were in the low-response group (p < .01), and the PSV on the first day of the COH cycle have statistical significance in predicting the number of high-quality embryos. The number of cumulus oophorus on the day of hCG injection has statistical significance in predicting the number of oocytes retrieved and fertilised oocytes. We conclude that the ovarian stromal artery flow parameters on the first day of the COH cycle and cumulus oophorus count on hCG injection day can serve as efficient indicators for an early assessment of ovarian response and individualised ovulation induction. IMPACT STATEMENT What is already known on this subject? AMH, AFC, and the age of the patient are well-known effective parameters for the evaluation of ovarian response, but these are insufficient and full of individual differences. Some researchers have investigated the value of colour Doppler ultrasound and cumulus oophorus in assessing ovarian response, but no definitive conclusion has been reached. What do the results of this study add? The hemodynamic parameters of ovarian stromal artery on the first day of the COH cycle and the number of cumulus oophorus on the day of hCG injection detected by Transvaginal Colour Doppler Sonography (TV-CDS) could be used to predict the ovarian response. What are the implications of these findings for clinical practice and/or further research? Ovarian stromal artery flow parameters and cumulus oophorus detected by TV-CDS can potentially be offered as a complementary parameter for ovarian reserve.

Analysis of maturation dynamics and developmental competence of in vitro matured oocytes under time-lapse monitoring

BackgroundTo improve the developmental competence of in vitro cultured oocytes, extensive literature focused on maturation rate improvement with different additives in culture medium, while studies investigating the maturation dynamics of oocytes during in vitro maturation (IVM) and the influencing factors on oocyte viability are scarce.MethodsThe study involved a retrospective observation by time-lapse monitoring of the IVM process of 157 donated GV oocytes from 59 infertile couples receiving ICSI in 2019, in Tongji Hospital, Wuhan, China. The GV oocytes derived from controlled ovarian hyperstimulation (COH) cycles underwent rescue IVM (R-IVM), and the maturation dynamics, including GVBD time (GV-MI), time from GVBD to maturation (MI-MII), maturation time (GV-MII), and MII arrest duration (MII-ICSI), were recorded by time-lapse monitoring. The matured oocytes were inseminated at different MII arrest points and subsequent embryo developments were assessed. The effects of baseline clinical characteristics, oocyte diameters, and maturation dynamics on the developmental competence of the oocytes were also analyzed.ResultsTotally, 157 GV oocytes were collected. GVBD happened in 111 oocytes, with a median GV-MI duration of 3.7 h. The median MI-MII duration was 15.6 h and the median GV-MII duration was 19.5 h. The maturation rate reached 56.7% at 24 h and 66.9% at 48 h, and the clinical factors, including patient age, FSH level, AMH level, ovarian stimulation protocol, and serum estradiol and progesterone levels on hCG trigger day, showed no effects on the 24-h maturation rate. The normal fertilization rate of oocytes resuming meiosis within 8 h and matured within 24 h was significantly higher than that of oocytes resuming meiosis after 8 h and matured after 24 h. Furthermore, among those oocytes matured within 24 h, the high-quality embryo formation rate of oocytes resuming meiosis within 4.5 h and matured within 19 h was significantly higher. All stated time was measured from the start point of IVM. Additionally, for oocytes from patients with serum progesterone levels less than 1 ng/ml on hCG trigger day, the high-quality embryo formation rate was significantly increased.ConclusionR-IVM technology could increase the available embryos for patients in routine COH cycles, but excessive culture beyond 24 h is not recommended. GV-MI duration of the oocyte, recorded by time-lapse system, and serum progesterone levels of patients on hCG trigger day can significantly affect the developmental potential of the IVM oocytes.

Serum Sex Hormone Binding Globulin Concentration as a Predictor of Ovarian Response During Controlled Ovarian Hyperstimulation.

Purpose: Serum concentrations of sex hormone binding globulin (SHBG), a glycated homodimeric plasma transport protein, correlate positively with the total number of follicles in women with infertility. However, the relationship between serum SHBG concentrations and the ovarian response during controlled ovarian hyperstimulation (COH) and whether this relationship differs between women with and without polycystic ovary syndrome (PCOS) remains unclear.Methods: The study cohort included 120 participants (60 non-PCOS and 60 PCOS) undergoing in vitro fertilization. Serum samples were collected from each participant every 2–3 days during the COH cycle. The concentrations of serum SHBG and other sex hormones were determined to investigate the relationship between serum SHBG concentrations and the ovarian response in women with and without PCOS.Results: We found that the serum SHBG concentration was positively correlated with the ovarian response in non-PCOS patients but not in PCOS patients.Conclusion: The serum SHBG concentration may be clinically useful as a predictor of the ovarian response during COH in patients without PCOS.

Prior iodine exposure and impact on thyroid function during controlled ovarian hyperstimulation: A prospective study.

Iodine supplements are recommended for women planning pregnancy, but their impact on thyroid function during controlled ovarian hyperstimulation (COH) and into pregnancy is unknown. The aim of this study was to assess the impact of iodine supplementation on thyroid function during COH. One-hundred and six euthyroid women (thyroid stimulating hormone (TSH) 0.4-2.5mIU/L) planning their first COH cycle were subdivided according to iodine supplementation (nil, <6months, ≥6months) and compared to levothyroxine (LT4)-treated controls. Serial TSH, free thyroxine, free triiodothyronine and thyroglobulin (Tg) levels were recorded at four time points: (i) baseline, (ii) day 7 ovarian stimulation, (iii) ovulation trigger and (iv) two weeks post oocyte retrieval. Oocyte numbers, fertilisation rates and pregnancy outcome were recorded. TSH increased during COH for those women taking iodine supplements for ≥6months (P=0.025). One quarter recorded a TSH level >2.5mIU/L before embryo transfer. A similar increase in TSH was demonstrated by LT4-dependent controls (P=0.024) but not the remaining subgroups. Tg levels did not change during COH in any group but decreased significantly post oocyte retrieval if nil iodine (P<0.0001) or supplemented for ≥6months (P<0.005). Iodine supplementation did not influence oocyte count, fertilisation or implantation rates. Women taking iodine for <6months were four times more likely to achieve a live birth than women taking iodine for longer. Women taking iodine supplements for ≥6months are less able to adapt to the thyroidal demands of COH, with responses comparable to LT4-dependent patients.

P–440 Seven years’ experience using oocyte vitrification/warming from in vitro maturation or controlled ovarian hyperstimulation cycles to preserve fertility for oncologic indications

Abstract Study question Do oocytes vitrified following in vitro maturation (IVM) or controlled ovarian hyperstimulation (COH) for oncologic fertility preservation (FP), lead to similar biological/clinical outcomes after thawing? Summary answer IVM is a valid option when chemotherapy is urgent or COH is contraindicated. We report the second live-birth worldwide after IVM in a cancer patient. What is known already FP aims at maintaining in cancer survivors, the possibility of childbearing using their own gametes. Currently, oocyte vitrification after COH remains the gold standard but IVM has recently emerged as an option for young women seeking FP, when COH is contraindicated or when cancer therapy is urgent. However, the actual competence of oocyte vitrified after IVM in cancer patients is not established. To date, only one live birth has been reported following frozen/warmed oocytes from an IVM cycle and no data is available comparing biological/clinical outcomes of warmed oocytes resulting either from IVM or COH cycles in cancer survivors. Study design, size, duration This retrospective cohort study from a single IVF unit aimed to analyze outcomes of all oocyte warming cycles in 38 cancer survivors having undergone oocyte vitrification for FP after COH or IVM. All of them had oocyte retrieval before administration of gonadotoxic treatment and returned after being cured for assisted reproduction treatments with their oncologist agreement, between January 2014 and December 2020. Participants/materials, setting, methods Thirty-eight oocytes warming cycles followed by ICSI respectively from 18 COH and 22 IVM cycles were analyzed. Survival, degeneration following ICSI, fertilization, top-quality and good-quality embryos, defined at day–2 respectively as 4 and 3–5 adequate-sized blastomeres, without multinucleation and containing &amp;lt;20% of cytoplasmic fragments, implantation, biochemical (hCG&amp;gt;100 UI/mL), clinical (intrauterine sac with fetal heart beat) and live birth rates were compared between IVM and COH cycles using appropriate statistical tests. Significance was set at 5%. Main results and the role of chance The indications for FP were breast cancer (n = 32), hematologic malignancies (n = 3), BRCA1 mutation (n = 2), borderline ovarian tumor (n = 1). The mean age and antral follicle count (AFC) at the time of FP was similar in both groups. The number of cryopreserved oocytes was significantly lower in the IVM group (5.7 ± 9.1) when compared with the COH group (11.4 ± 3.3; p = 0.009). Oocyte survival rates were similar in IVM (70 ± 24%) and COH groups (73 ± 28%). Although not significant, we reported a trend to better results in the COH group when compared with those of IVM group in terms of degeneration rate following ICSI (6 ± 10% vs. 14 ± 20%; p = 0.16), fertilization (72 ± 35% vs. 54 ± 27%; p = 0.08), day 2 top-quality (38 ± 32% vs. 21 ± 31%; p = 0.15) and good-quality embryo (46 ± 30% vs. 25 ± 30%; p = 0.06), implantation (18 ± 35% vs. 14 ± 36%; p = 0.79), biochemical (28 (5/18) vs. 14% (3/22); p = 0.26), clinical (22% (4/18) vs. 9% (2/22); p = 0.24), live birth rates (22% (4/18) vs. 5% (1/22); p = 0.06). Limitations, reasons for caution Caution is needed when interpreting these retrospective data obtained from a limited number of frozen-thawed cycles. Statistical power to compare IVF outcomes after COH and IVM is limited by the few women who return for oocyte reutilization. Wider implications of the findings: The present investigation is the largest evaluating the IVM-oocyte frozen-thawed cycles in a oncologic population. It suggests that a higher oocyte yield may be necessary in IVM, since fertilization/embryo-quality rates seem lower. Success rates and limiting factors of oocyte vitrification in this context is needed for providing proper oncofertility counseling. Trial registration number Not applicable

Acupuncture for Poor Ovarian Response: A Randomized Controlled Trial.

Acupuncture is believed to improve ovarian reserve and reproductive outcomes in women undergoing in vitro fertilization (IVF). This study was conducted to evaluate the effect of network-optimized acupuncture followed by IVF on the oocyte yield in women showing a poor ovarian response. This study was an exploratory randomized controlled trial conducted from June 2017 to January 2020 at the Pusan National University Hospital. Women diagnosed with poor ovarian response were enrolled and randomly divided into two groups: IVF alone and Ac + IVF groups (16 acupuncture sessions before IVF treatment). Eight acupoints with high degree centrality and betweenness centrality were selected using network analysis. Among the participants, compared with the IVF treatment alone, the acupuncture + IVF treatment significantly increased the number of retrieved mature oocytes in women aged more than 37 years and in those undergoing more than one controlled ovarian hyperstimulation cycle. The negative correlation between the number of retrieved mature oocytes and consecutive controlled ovarian hyperstimulation cycles was not observed in the Ac + IVF group irrespective of the maternal age. These findings suggest that physicians can consider acupuncture for the treatment of women with poor ovarian response and aged > 37 years or undergoing multiple IVF cycles.

The effects of multiple controlled ovarian hyperstimulation over a 2-year period on ovarian reserve and reactivity: a retrospective clinical study

To evaluate the effects of controlled ovarian hyperstimulation (COH) on ovarian reserve function during in vitro fertilization and embryo transfer (IVF-ET). From August 2018 to August 2020, the medical records of patients who received IVF-ET in the Department of Reproductive Medicine, Beijing Gynaecology and Obstetrics Hospital, Capital Medical University were analyzed retrospectively. Among them, 372 patients received 2 cycles of COH, 54 patients received 3 cycles, and 13 patients received 4 cycles. The levels of follicle-stimulating hormone (FSH), the number of antral follicles, levels of anti-Müllerian hormone (AMH), the total amount of gonadotropin (GN), the time of ovulation induction, the number of eggs obtained, the number of available embryos, and the number of high-quality embryos cycles were compared in different treatment. The age of female patients did not significantly affect the levels of AMH or FSH during menstruation, nor the number of antral follicles before ovulation induction (P>0.05). However, with an increase in age, an increase in the number of controlled COH cycles was observed. In patients who underwent 2 COH cycles, the number of high-quality embryos in the second cycle increased significantly compared to the first cycle (P<0.05). However, there were no significant differences in the ovulation induction time, the number of eggs, the GN dosage, and the number of available embryos (P>0.05). In patients with 3 treatment cycles, the GN dose used in the third cycle was significantly lower than that used in the first cycle (P<0.05). There were no significant differences in the ovulation induction time, the number of eggs obtained, and the quality of embryos (P>0.05). In patients with 4 treatment cycles, significant differences were observed in the ovulation induction time between the first and the fourth controlled COH cycle (P<0.05). However, no significant differences were detected in GN dosage, ovulation induction time, the number of eggs obtained, the number of available embryos, and the quality of embryos (P>0.05). Ovarian reserve function was not significantly affected in patients with up to 4 ovarian stimulation cycles.

UNIVERSAL SEVERE ACUTE RESPIRATORY SYNDROME CORONAVIRUS 2 (SARS-COV-2) TESTING IN A NEW YORK CITY REPRODUCTIVE MEDICINE PRACTICE

To describe our single-center experience and results of universal SARS-CoV-2 testing in asymptomatic patients undergoing controlled ovarian hyperstimulation (COH). Retrospective cohort study conducted at a university-affiliated center. On March 21, 2020, New York-Presbyterian Hospital, where our retrieval suite is located, instituted a policy of universal SARS-CoV-2 testing prior to surgical procedures requiring anesthesia. As a result, we began testing all patients undergoing COH for SARS-CoV-2 using reverse transcription-polymerase chain reaction via nasopharyngeal swabs (Roche Cobas 6800). Tests were performed on the morning of cycle start and repeated 24 hours before oocyte retrieval. A positive test at either time point excluded patients from continuing with treatment. During the testing period, all patients and staff were required to wear surgical masks at all times when at our center and consented to symptom and temperature screening at every monitoring visit. Between March 21 and May 20, 2020, 169 asymptomatic patients underwent nasopharyngeal swabs at cycle start, four of which returned positive for SARS-CoV-2 for a center prevalence of 2.4%. All four patients were asymptomatic at the time of cycle start and were not permitted to begin their COH cycle. One of these patients had previously had a positive PCR swab over 60 days prior and had been symptom-free during this interval. One patient with a negative PCR swab on cycle start subsequently converted to positive 15 days later on her PCR swab prior to retrieval, despite the absence of COVID-19 symptoms. Per our hospital policy, she was not allowed to proceed with oocyte retrieval and was started on a course of daily GnRH antagonist and asked to abstain from intercourse for 14 days. None of the 5 patients went on to develop COVID-19 symptoms following their positive test result. All patients were referred to follow-up with their primary care provider. Prior to returning for further COH treatment, all patients will be required to undergo repeat PCR testing with a negative result. While rare, asymptomatic carriers of the SARS-CoV-2 virus were identified for a center prevalence of 2.4% in patients undergoing COH. Despite initial negative PCR testing, patients may convert to positive over the course of a COH cycle and not demonstrate symptoms. Strict personal protective equipment and social distancing use is essential to protect patients and staff alike.

Late follicular phase progesterone elevation during ovarian stimulation is not associated with decreased implantation of chromosomally screened embryos in thaw cycles

What is the impact of a late follicular phase progesterone elevation (LFPE) during controlled ovarian hyperstimulation (COH) on embryonic competence and reproductive potential in thaw cycles of preimplantation genetic testing for aneuploidy (PGT-A) screened embryos? Our study findings suggest that LFPE, utilizing a progesterone cutoff value of 2.0 ng/ml, is neither associated with impaired embryonic development, increased rate of embryonic aneuploidy, nor compromised implantation and pregnancy outcomes following a euploid frozen embryo transfer (FET) cycle. Premature progesterone elevation during COH has been associated with lower pregnancy rates due to altered endometrial receptivity in fresh IVF cycles. Also, increased levels of progesterone (P) have been suggested to be a marker for ovarian dysfunction, with some evidence to show an association between LFPE and suboptimal embryonic development. However, the effect of LFPE on embryonic competence is still controversial. Retrospective cohort analysis in a single, academic ART center from September 2016 to March 2020. In total, 5244 COH cycles for IVF/PGT-A were analyzed, of those 5141 were included in the analysis. A total of 23991 blastocysts underwent trophectoderm biopsy and PGT analysis. Additionally, the clinical IVF outcomes of 5806 single euploid FET cycles were evaluated. Cohorts were separated in two groups: Group 1: oocytes retrieved from cycles with normal P levels during ovulation trigger (P ≤ 2.0 ng/ml); Group 2: oocytes retrieved after cycles in which LFPE was noted (P > 2.0 ng/ml). Extended culture and PGT-A was performed. Secondly, IVF outcomes after a single euploid FET were evaluated for each cohort. Four thousand nine hundred and twenty-five cycles in Group 1 were compared with 216 cycles on Group 2. Oocyte maturity rates, fertilization rates and blastulation rates were comparable among groups. A 65.3% (n = 22654) rate of utilizable blastocysts was found in patients with normal P levels and were comparable to the 62.4% (n = 1337) observed in those with LFPE (P = 0.19). The euploidy rates were 52.8% (n = 11964) and 53.4% (n = 714), respectively, albeit this difference was not statistically significant (P = 0.81). Our multivariate analysis was fitted with a generalized estimating equation (GEE) and no association was found with LFPE and an increased odds of embryo aneuploidy (adjusted odds ratio 1.04 95% CI 0.86-1.27, P = 0.62). A sub-analysis of subsequent 5806 euploid FET cycles (normal P: n = 5617 cycles and elevated P: n = 189 cycles) showed no differences among groups in patient's BMI, Anti-Müllerian hormone (AMH), endometrial thickness at FET and number of prior IVF cycles. However, a significant difference was found in patient's age and oocyte age. The number of good quality embryos transferred, implantation rate, clinical pregnancy rate, ongoing pregnancy rate, multiple pregnancy rate and clinical pregnancy loss rates were comparable among groups. Of the registered live births (normal P group: n = 2198; elevated P group: n = 52), there were no significant differences in gestational age weeks (39.0 ± 1.89 versus 39.24 ± 1.53, P = 0.25) and birth weight (3317 ± 571.9 versus 3 266 ± 455.8 g, P = 0.26) at delivery, respectively. The retrospective nature of the study and probable variability in the study center's laboratory protocol(s), selected progesterone cutoff value and progesterone assay techniques compared to other ART centers may limit the external validity of our findings. Based on robust sequencing data from a large cohort of embryos, we conclude that premature P elevation during IVF stimulation does not predict embryonic competence. Our study results show that LFPE is neither associated with impaired embryonic development nor increased rates of aneuploidy. Embryos obtained from cycles with LFPE can be selected for transfer, and patients can be reassured that the odds of achieving a healthy pregnancy are similar to the embryos exposed during COH cycles to physiologically normal P levels. No funding was received for the realization of this study. Dr A.B.C. is advisor and/or board member of Sema 4 (Stakeholder in data), Progyny and Celmatix. The other authors have no conflicts of interest to declare. NA.

A Comparison of Embryonic Development and Clinical Outcomes between In vitro Oocytes Maturation Using Micro-Vibration System and In vivo Oocytes Maturation in Polycystic Ovarian Syndrome Patients

Background/Objectives: Mechanical micro-vibration remains insufficient for improving embryo culture conditions in human immature oocytes. This study compared the clinical outcomes and embryo development between germinal vesicle (GV) oocytes with the micro-vibration culture (MVC) system in in vitro maturation (IVM) cycles and in vivo-matured oocytes in controlled ovarian hyperstimulation (COH) cycles in polycystic ovarian syndrome (PCOS) patients. Methods: This study investigated 152 PCOS patients who underwent 159 fresh embryo transfer cycles, including IVM cycles with embryos derived from GV oocytes and the COH cycles with embryos derived from in vivo-matured oocytes. The IVM cycles were divided into groups according to the culture system used: static culture (SC) and MVC: In the IVM-S group (n = 47), SC was applied during both IVM and in vitro culture (IVC), whereas in the IVM-MV group (n = 44), MVC was applied during both IVM and IVC. For the COH cycles, in the COH-S group (n = 68), SC was applied during IVC. Results: The number of in vitro-matured oocytes was similar in the IVM-S and IVM-MV groups, but the good-quality embryo (GQE; ≥6-cells) rate was significantly higher in the IVM-MV group (p < 0.01). The GQE rate and clinical outcomes of the COH-S group were significantly better than those of the IVM-S group (p < 0.05) but similar to those of the IVM-MV group. Conclusion: Compared with the SC system, the MVC system in IVM cycles improves the embryonic quality of GV oocytes and clinical outcomes, resulting in development of potential equivalent to in vivo-matured oocytes.

Melatonin promotes the development of immature oocytes from the COH cycle into healthy offspring by protecting mitochondrial function.

Melatonin (MT) regulates reproductive performance as a potent antioxidant; however, its beneficial effects on oocyte development remain largely unknown, especially in human oocytes. The collected 193 immature oocytes from the controlled ovarian hyperstimulation (COH) cycle underwent in vitro maturation (IVM) in IVM medium contained 10μmol/L MT (n=105, M group) and no MT (n=88, NM group), followed by insemination and embryo culture. The results showed that the high-quality blastocyst formation rate in the M group (28.4%) was significantly higher than that in the NM group (2.0%) (P=.0001), and the aneuploidy rate was low (15.8%). In the subsequent clinical trials, three healthy infants were delivered. Next, single-cell RNA-seq data revealed 1026 differentially expressed genes (DEGs) between the two groups, KEGG enrichment analysis revealed that the majority of DEGs involved in oxidative phosphorylation pathway, which associated with ATP generation, was upregulated in the M group. Finally, confocal fluorescence staining results revealed that the mitochondrial membrane potential in the oocytes significantly increased and intracellular ROS and Ca2+ levels greatly decreased in the M group. Melatonin can promote the development of immature human oocytes retrieved from the COH cycle into healthy offspring by protecting mitochondrial function.