Hyperstimulation Cycles Research Articles

Ovarian response in preimplantation genetic testing for myotonic dystrophy type 1.

To evaluate ovarian stimulation response in couples undergoing preimplantation genetic testing (PGT-M) for myotonic dystrophy type 1 (DM1) METHODS: Retrospective, observational, multicentric study. Parameters of ovarian response and PGT-M outcomes were compared according to the DM1-affected patient (female or male). A total of 229 couples underwent at least one controlled ovarian hyperstimulation cycle for the PGT-M procedure. Overall, 678 COS cycles were started, leading to 560 cycles with oocyte retrievals and subsequent PGT-M analysis. At the time of the first PGT-M attempt, affected DM1 females were 1 year older and their serum AMH level was significantly lower than that of the healthy partner of affected DM1 males. After higher starting and total doses of exogenous gonadotropins, the number of mature oocytes was not statistically different between both groups (9 [6-13] vs 9 [6-13] mature oocytes, p=0.73). The FORT index was similar in both groups (35.2% [19.2-52.8] vs 33.3% [19.6-50.0], p=0.09), suggesting that antral follicle responsiveness to FSH is not altered. The live birth rate per fresh embryo transfer was 23.8% in the affected females group and 27.6% for the affected males. After adapted controlled ovarian stimulation protocol and starting dose, a similar response (number of mature oocytes) and sensitivity (FORT index) was observed in DM1 females when compared to healthy partners of DM1 males undergoing PGT-M.

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

Impact of repeated ovarian hyperstimulation on the reproductive function

One of six couples (17.5 % of the adult population) worldwide is affected by infertility during their lifetime. This number represents a substantial increase in the prevalence of this gynecological condition over the last decade. Ovulatory dysfunction and anovulation are the main causes of female infertility. Timed intercourse, intrauterine insemination, and assisted reproductive technology (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), are the most common interventions for infertile couples. Ovulation induction protocols for IVF/ICSI routinely use supraphysiological doses of gonadotropins to stimulate many preovulatory follicles. Animal and human studies suggested that ovarian hyperstimulation, alone or repeatedly, for ART cycles can induce changes in the immune response and increase the oxidative stress (OS) in the ovarian microenvironment. The consequences of repeated ovarian hyperstimulation on the human ovary remain poorly understood, particularly in relation to the effects of ovarian stimulation on the immune system and the potential for ovarian stimulation to cause OS. Animal studies have observed that repeated cycles of ovarian hyperstimulation can accelerate ovarian aging. Changes in ovarian hormone levels, accelerated loss of ovarian reserve, disorders in ovarian ultrastructure, ovarian senescence, and decreased reproductive performance represent possible long-term effects of repeated ovarian hyperstimulation. The short and long-term impact of the combination of antioxidant agents in ovarian hyperstimulation protocols in women undergoing ART must urgently be better understood. The recent increase in the number of ART and fertility preservation cycles may accelerate ovarian aging in these women, promoting consequences beyond the reproductive function and including health deterioration.

Assessment of Repetitive Controlled Ovarian Stimulation (COS) Cycles on Oocyte Donors: Impact on Oocyte Quality and Viable Embryo Yield

The utilization of donor eggs has broadened the options for Assisted Reproductive Technology (ART) among women facing challenges with egg quantity or quality. Given that donors are typically selected from young and fertile individuals, In Vitro Fertilization with egg donation (IVF-ED) tends to exhibit higher rates of implantation, pregnancy, and live births compared to IVF with the woman's own eggs, especially for females over 35 years old. This has led to a projected increase in the demand for IVF-ED, surpassing the number of available donors. Consequently, many centers opt to use oocyte donors for multiple cycles. However, the correlation between repeated Controlled Ovarian Stimulation (COS) cycles and the performance of donors in terms of viable blastocyst stage embryo (VEC) or blastocyst embryo rate is not definitively established and remains of interest. This study aims to explore the preimplantation characteristics of embryo development and oocyte maturation status based on the number of donor COS cycles, employing a Generalized Linear Mixed Model (GLMM) framework. The study encompasses 1965 embryo transfer (ET) cycles involving 399 donors who underwent a minimum of two and a maximum of nine controlled ovarian hyperstimulation (COS) cycles. The findings indicate that, with the patient undergoing six or more cycles of ovarian stimulation, despite a 3.9% increase in both maturation and fertilization rates, there is a corresponding decrease of 4.5% in VEC rate and 4.7% in blastulation rates. In essence, an escalating number of donor COS cycles appears to be associated with a disadvantageous reduction in embryo quality.

C-phycocyanin improves the developmental potential of cryopreserved human oocytes by minimizing ROS production and cell apoptosis.

The cryopreservation process damages oocytes and impairs development potential. As a potent antioxidant, C-phycocyanin (PC) regulates reproductive performance. However, its beneficial effects on vitrified human oocytes remain unknown. In this study, human GV-stage oocytes obtained from controlled ovarian hyperstimulation (COH) cycles were randomly allocated to three groups: fresh oocyte without freezing (F group), vitrification in medium supplemented with PC (P group), and vitrification in medium without PC as control group (C group). After warming, viable oocytes underwent in vitro maturation. Our results showed that 3 μg/mL PC treatment increased the oocyte maturation rate after cryopreservation. We also found that PC treatment maintains the regular morphological features of oocytes. After PC treatment, confocal fluorescence staining showed a significant increase in the mitochondrial membrane potential of the vitrified oocytes, along with a notable decrease in intracellular reactive oxygen species and the early apoptosis rate. Finally, after in vitro maturation and parthenogenetic activation, vitrified oocytes had a higher potential for cleavage and blastocyst formation after PC treatment. Our results suggest that PC improves the developmental potential of cryopreserved human GV-stage oocytes by attenuating oxidative stress and early apoptosis and increasing the mitochondrial membrane potential.

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.

#114 : Is Mild Stimulation IVF Better for Women with Previous Poor Outcome Following Conventional High-Dose Stimulation?

Background and Aims: With the aim of yielding higher number of oocytes, high gonadotrophin doses are often used in ovarian stimulation protocols which may have a detrimental impact on oocyte and subsequently embryo quality. Alternatively, mild stimulation (MS) protocols mimic physiological folliculogenesis with a low dosage of gonadotropins and aims to produce better-quality oocytes with a reduced aneuploidy rate. This study investigates the clinical outcome of patients who had multiple attempts of IVF cycles with both MS and high-dose conventional stimulation (HS) protocol. Method: A retrospective analysis was carried out on 26 patients who had a total of 108 IVF cycles from 2017-2022. The MS protocol involves administration of Letrozole/Clomiphene from Day 2 for 5 days followed by highly purified menotrophin (150-225IU) on alternate days starting after Day 3 whereas in HS protocol, [Formula: see text]300IU of daily dose of gonadotrophins were given. ICSI was performed for all mature oocytes and the resulting embryos were cultured to blastocyst stage for preimplantation genetic testing for aneuploidy (PGT-A). Clinical outcomes such as the rate of fertilisation, degeneration, blastocyst utilisation, aneuploidy, clinical pregnancy, and live birth were analysed with Chi-square and Fisher’s exact test. Results: The fertilisation rate (p=0.00140) and blastocyst utilisation rate (p=0.00966) are significantly higher with MS compared to the HS protocol. The degeneration rate did not differ among the treatments (p=0.50248). The pregnancy and live birth rates are higher following MS compared to HS but this is not statistically significant due to low number of patients. Aneuploidy rate is shown to be significantly higher in HS compared to MS (p=0.00975). On average, 3 cycles of MS are required to produce a live birth. Conclusion: Patients with poor outcome to conventional hyperstimulation cycles may benefit from MS protocols. MS is cost-effective with lower treatment burden and has been shown in this small study to produce better clinical outcomes.

Successful pregnancy and delivery in a female with pituitary stalk interruption syndrome following in vitro fertilization and embryo transfer: A case report and literature review.

Pituitary stalk interruption syndrome (PSIS) in female patients is mainly characterized by short stature, primary amenorrhea, absent or incomplete sexual maturation, and infertility. Successful pregnancies among these patients are rare. In this report, we describe a successful pregnancy and delivery in a 28-year-old Chinese woman with PSIS following in vitro fertilization and embryo transfer. The patient exhibited typical symptoms, including multiple pituitary hormone deficiency, typical triad signs in magnetic resonance imaging (MRI), undetectable serum gonadotropins and estradiol levels, and invisible antral follicles in both ovaries. During the first attempted controlled ovarian hyperstimulation cycle, 14 oocytes were retrieved and six embryos were acquired. Artificial endometrial preparation and frozen-thawed embryo transfer were performed, resulting in a clinical pregnancy after the transfer of a day 5 blastocyst. The patient was closely monitored throughout the pregnancy and multiple hormone dosages were modulated accordingly. She delivered a healthy boy by elective cesarean section, and the newborn developed normally during a 1-year follow-up period. This is the first report of a successful live birth in a woman with PSIS achieved through in vitro fertilization and frozen-thawed embryo transfer. A literature review on this topic is also presented.

Comparison between Agonist Trigger with HCG Luteal Phase Supplementation vs HCG Trigger with Progesterone Luteal Phase Supplementation in Antagonist Controlled Hyperstimulation Cycle Regarding Clinical Pregnancy Rate

For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the comparison between conventional HCG trigger and progesterone luteal phase support vs Agnosit trigger and HCG microsdose luteal phase support as regards to pregnancy rate. Methods 100 patients were recruited for this trial Cases with Polycyctic ovaries were excluded from the study. The study was approved by Ethical committee of Ain Shams university. Patients received Gonal-F (Merck Serono S.p.A., Via delle Magnolie 15, I70026 Modugno (Bari), Italy.) in a dose ranginging between 150-300 IU for stimulation and the dose was adjusted according to response starting day 6. Premature LH surge was prevented with 0.25 mg of a GnRH antagonist (Cetrotide; Merck international) starting on day 6, when two or more follicles reach a size of 18–20 mm, patients were randamized into 2 groups of 50 each. Trigger of ovulation was done by a single dose of 0.2 mg triptorelin (Decapeptyl®ferring pharmaceutical company, Germany) and luteal phase support with daily 125 IU HCG injections in Group 1. Group 2 received A single dose of HCG 10000 IU was given followed by progesterone supplementation with 100mg IM progesterone (Prontogest® IBSA Swisserland). 2 Embryo were transferred and an ultrasound at 4 weeks after embryo transfer for cases with positive pregnancy test. As regards to clinical pregnancy group 1 had 28 of the 50 (56%) Positive clinical pregnancy while control was 26 of the 50 (52%), the difference was not statistically significant (P &amp;gt; 0.68). No cases of moderate or severe ovarian hyperstimulation were observed during the study. To conclude, Agonist trigger combined with microdose HCG had a comparable pregnancy rate resulst to HCG trigger and conventional progesterone support for luteal support without increasing the risk of ovarian hyper stimulation.

P-679 Controlled ovarian stimulation using follitropin delta results in higher cumulative live birth rate compared to follitropin alfa/beta in a large prospective real world dataset

Abstract Study question Does IVF/ICSI-treatment using follitropin delta (hrFSH) result in higher pregnancy rates (PR) or live birth rates (LBR) compared to follitropin alfa/beta (recFSH)? Summary answer Real world data (RWD) from a large prospective German registry study shows that using hrFSH results in higher pregnancy rates compared to recFSH. What is known already Follitropin delta represents a new recombinant FSH derived from a human cell line. Contrary to follitropin alfa or beta, follitropin delta has a glycolysation pattern consisting of α2,3- and α2,6-linked sialic acids which is more similar to native human FSH. Follitropin delta is approved for use with an individualized dosing algorithm based on serum AMH and body weight, targeting an optimal ovarian response (8-14 oocytes). Efficacy and safety have been demonstrated in numerous clinical trials. Moreover, Follitropin delta seems to reduce the risk of OHSS although its safety with respect to ovarian hyperstimulation using RWD remains to be investigated. Study design, size, duration The German IVF Registry collects prospectively data about IVF/ICSI-treatments from 140 German IVF centers. The underlying analysis of RWD includes controlled ovarian hyperstimulation cycles that have been performed in Germany between 2017-2021. Study groups were built subject to the gonadotropin used for stimulation, irrespective of previous treatments: (1) hrFSH, n = 3002, (2) recFSH, n = 135293. “Pregnancy” was defined as clinically assessed, intrauterine pregnancy, including miscarriages. Biochemical pregnancies were not defined as “pregnant”. Ectopic pregnancies (n = 558) were excluded. Participants/materials, setting, methods PR and LBR were calculated subject to the number of embryo transfers (ET) (n = 2062 (rFSH) vs. n = 103357 (recFSH)) after excluding freeze-all cycles, (n = 529 (hrFSH) vs. n = 13682 (recFSH)) and cycles that ended without ET (n = 411 (hrFSH) vs. n = 18254 (recFSH)). The collected data were saved in compliance with the applicable data processing regulations. Statistical analysis was performed using Fishers-exact- and students-t-test and Microsoft Excel, whereas p &amp;lt; 0.05 was defined as significant. Main results and the role of chance There was no difference between the study groups regarding age (33.9 ± 4.00y (hrFSH) vs. 33.8y±4.34y (recFSH), p = 0.12) or infertility diagnosis. Stimulation with hrFSH resulted in a higher number of oocytes (11.15±7.2 vs. 10.39±7.01, p &amp;lt; 0.01). Antagonist protocol was used less often in the hrFSH-group (78% (2344/3002 vs. 80% (109217/135293), p &amp;lt; 0.01). PR in 2021 were higher (39.2% (222 pregnancies / 567 embryo transfers) vs. 35.2% (6837/19420), OR = 1.18 [0.99-1.41] p = 0.05) while using hrFSH compared to recFSH. The effect was even stronger when comparing patients aged 30-34y (46.2% (98/212) vs. 38.6% (2967/7865), OR = 1.41 [1.07-1.88], p = 0.01). Another quantitative difference could be observed for patients aged 30-34y in their first IVF/ICSI-cycle (PR 48.5% (63/130) vs. 39.5% (1926/4873), OR = 1.44 [1.00-2.07], p = 0.05). Including all cycles between 2017-2021 resulted in higher PR for couples treated with hrFSH (38.3% (790/2062) vs. 36.2% (37439/103357), OR = 1.09 [1.00-1.20], p = 0.049). Cumulative PR including consecutive frozen embryo transfers after the first stimulation showed significantly higher PR while using hrFSH (81.6% (422/517) vs. 71.3% (17373/24367), OR = 1.79 [1.42-2.23], p &amp;lt; 0.01). Finally, cumulative LBR per ET was significantly increased if hrFSH was used for ovarian stimulation (60.0% (310/517) vs. 51.9% (12648/24367), OR = 1.39 [1.16-1.66], p &amp;lt; 0.01) compared to recFSH. Limitations, reasons for caution Since we analyzed RWD, comparison with large clinical trials should be considered carefully. PR and LBR was calculated only using stimulations which successfully generated ET. Moreover, individual AMH values are not transmitted to the German IVF Registry. Therefore, difference in ovarian reserve between study groups can’t be excluded. Wider implications of the findings In this large, prospective RWD, higher cumulative LBR and PR using hrFSH compared to recFSH, irrespective of age or infertility diagnosis, supports the use of individualized fertility treatment approach based on hrFSH. These results are consistent with previous retrospective findings. Trial registration number Not applicable

How to dose follitropin delta for the first insemination cycle according to the ESHRE and ASRM guidelines; a retrospective cohort study

BackgroundFollitropin Delta (FD) is indicated exclusively for in-vitro fertilization however, being a gonadotropin it could be used for other purposes. A dosing algorithm exists for FD and IVF but is needed for intrauterine insemination (IUI) cycles. The objective of this study is to determine dosing for FD for the first controlled ovarian hyperstimulation (COH) cycle according to current stimulation guidelines.ResultsA retrospective study of 157 subjects from a single university fertility center from January 2017 to March 2020, was performed. All patients stimulated with FD for IUI were included. The number of failed, normal, or overstimulation cycles was determined based on stimulating not more than 2 mature follicles. We then stratified the group based on the AFC, AMH, and body weight. Of 157 subjects, 49% stimulated correctly, 5.6% failed and 45.4% overstimulated. An analysis of the COH IUI cycles based on stratification and over or lack of stimulation per published guidelines found that women with a bodyweight < 80 kg or AMH ≥ 1.5 ng/ml or AFC ≥ 10 initially stimulate with FD 2.0 to 3.0mcg daily. For women with an AFC of 6–9 stimulate with Follitropin Delta 3.0mcg daily. For women with an AFC < 6 or serum AMH < 1.5 ng/ml stimulate with FD 3.0–4.0mcg daily. For women with body weight > 80 kg stimulate initially with daily with 4.0–6.0mcg FD.ConclusionsFollitropin Delta can be used safely for controlled ovarian stimulation and insemination at doses easily dispensed by the current methods of delivery, within the current published guidelines for follicle development.

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.

ONE EPISODE OF SEVERE OVARIAN HYPERSTIMULATION SYNDROME (OHSS) IN AN OOCYTE DONOR INDICATES HIGH RISK FOR REOCCURRING SEVERE OHSS IN SUBSEQUENT OOCYTE DONATION CYCLES

While it is generally accepted that a prior history of severe OHSS is a risk factor for OHSS in subsequent cycles of ovarian hyperstimulation for in vitro fertilization (IVF), empirical evidence for this conjecture is lacking. Our objective was to evaluate OHSS risk according to the degree of OHSS experienced in initial cycles among donors undergoing multiple donation cycles.

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.

Reproductive endocrine characteristics and in vitro fertilization treatment of female patients with partial 17α-hydroxylase deficiency: Two pedigree investigations and a literature review

Background17α-hydroxylase/17, 20-lyase deficiency (17-OHD) is caused by the mutations of the CYP17A1 gene. The classical phenotype of 17-OHD includes hypertension, hypokalemia, and abnormal sexual development, with partial 17-OHD typically less severe than the complete deficiency. Infertility is always one of the main clinical manifestations of partial 17-OHD. However, to date, the pregnancy potentials of partial 17-OHD female patients have rarely been investigated, and few live-birth cases have been reported among them. Moreover, the reproductive endocrine characteristics of partial 17-OHD female patients have not been completely clarified and the treatment skills of in vitro fertilization and embryo transfer (IVF-ET) have not been well summarized yet.MethodsTwo Chinese infertile female patients clinically diagnosed as partial 17-OHD were enrolled and their pedigree investigations were performed. Hormones were determined to depict the endocrine conditions of partial 17-OHD female patients. The adrenocorticotropic hormone (ACTH) stimulation test was performed to evaluate the functions of the adrenal cortex. Genotype analysis was conducted by next-generation sequencing (NGS) and Sanger sequencing was used to verify the results. IVF-ET was performed for the treatment of their infertility. Specifically, the progestin-primed ovarian stimulation (PPOS) protocol was chosen for the controlled ovarian hyperstimulation (COH) cycles, and the hormone replacement treatment (HRT) protocol was adopted for the endometrial preparation in frozen–thawed embryo transfer (FET) cycles.ResultsHormone assays revealed a reduced estradiol (E2) and testosterone (T) level, and an elevated progesterone (P4) level. The classic ACTH stimulating test evidenced a suboptimal response of cortisol to ACTH. Genotype analysis demonstrated that the proband1 carried two variants: c.1459_1467del (p.Asp487_Phe489del)het and c.995T>C (p.lle332Thr)het. The proband2 was found to be a homozygote with the mutation of c.1358T>A (p.Phe453Ser)hom. The two female patients both succeeded in pregnancy and delivery of healthy babies through IVF-ET, with the usage of PPOS, HRT, and low-dose glucocorticoids.ConclusionsPartial 17-OHD female patients manifested menstrual cycle disorders and infertility clinically; displayed high P4 and low E2 and T; showed sparse pubic hair in physical examinations; and revealed multiple ovarian cysts in ultrasonic visualization. Moreover, the pregnancy potentials of infertile partial 17-OHD women seemed to increase with the adoption of IVF-ET. Considering the sustained elevated P4 level, PPOS is a feasible protocol for them in COH.

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-704 Post trigger progesterone levels as a predictor of oocyte recovery rate

Abstract Study question Do progesterone (P) levels the day after trigger for oocyte maturation impact the oocyte recovery rate? Summary answer A progesterone cutoff value of ≤ 5.0 ng/ml the day after trigger for oocyte maturation is associated with a lower oocyte recovery rate. What is known already Oocyte maturation and embryo development are controlled by intra-ovarian factors such as steroid hormones. P exists in the follicular fluid, and it is known to mediate some luteinizing hormone (LH)- initiated periovulatory events through autocrine/paracrine mechanisms that help mediate granulasa cell luteinization and oocyte maturation. More importantly, a rise in P levels is associated with an adequate follicular rupture. To date, no study has evaluated if lower P levels after oocyte maturation induction are a reflection of impaired physiological periovulatory mechanisms required for the oocyte release from the follicular wall. Study design, size, duration This monocentric retrospective analysis from January 2017 to December 2021 included 435 controlled ovarian hyperstimulation cycles for in vitro fertilization (IVF)/ egg freezing. Serum P, estradiol (E2), bHCG, and LH levels were measured the day after trigger for oocyte maturation to assure adequate luteinization. Participants/materials, setting, methods Women &amp;lt;4O years, that underwent controlled ovarian hyperstimulation with a GnRH antagonist protocol and final oocyte maturation (when ≥2 follicles reached ≥18 mm in diameter) induction with dual trigger (Leuprolide acetate and hCG) were segregated into two groups: Group 1: progesterone cutoff value of ≤ 5.0 ng/ml the day after trigger; Group 2: progesterone cutoff value of ≥ 5.1 ng/ml the day after trigger. Main results and the role of chance 147 cycles in Group 1 were compared with 288 cycles on Group 2. No significant differences were noted in mean patient’s age, BMI, baseline FSH, AMH, baseline antral follicle count, serum P and E2 levels the day of trigger, total dose of gonadotropins, day of trigger as well as serum E2, LH, and bHCG levels the day after trigger among cohorts. A total of 5765 oocytes were retrieved: 1703 corresponding to group 1 and 4692 to group B. Women with progesterone levels higher than ≥5.1 ng/ml the day after trigger had a greater number of oocytes retrieved compared to women with a progesterone cutoff value of ≤ 5.0 ng/ml (16.3 ± 9.1 versus 11.5 ± 7.4, p = &amp;lt; 0.0001). The oocyte/follicle rate was also significantly higher in women in Group 2 vs Group 1 (80.3% vs 63.7%, p = 0.003) However, the mature oocyte (MII) rate was comparable among cohorts (Group 1: 78.0 ± 20.2% vs Group 2: 78.8 ± 17.7%, p = 0.38). Limitations, reasons for caution The retrospective nature of the study, small sample size, selected progesterone cutoff value, and progesterone assay techniques compared to other ART centers may limit the external validity of our findings. Wider implications of the findings Our findings suggest for the first time that lower progesterone levels after final oocyte maturation induction may be a result of compromised mechanisms associated with the release of the oocyte from the follicular wall as demonstrated by a lower oocyte recovery rate. Trial registration number NA

Factors affecting clinical pregnancy in controlled ovarian hyperstimulation with GnRH-a long protocol: a retrospective cross-sectional study

This retrospective cross-sectional study was to investigate factors affecting clinical pregnancy in patients who received gonadotropin-releasing hormone agonist luteal phase long protocol (GnRH-a long protocol) and underwent fresh in-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) embryo transfer cycle. One thousand five hundred and twenty-five patients who received GnRH-a long protocol and underwent fresh IVF/ICSI embryo transfer cycle were enrolled. The clinical pregnancy rate (63.1 vs. 22.4%, p < .05) and live birth rate (53.8 vs. 14.5%, p < .05) were significantly higher while the miscarriage rate (12.5 vs. 35.3%, p < .05) was significantly lower in the two embryo group than those in the one embryo group. The clinical pregnancy rate (48.5 vs. 64.1%, p < .05) and live birth rate (38.4 vs. 55.0%, p < .05) were significantly lower in patients older than 33.5 years than those in younger patients. The clinical pregnancy rate (52 and 60.6 vs. 79.7%, p < .05) and live birth rate (36 and 51.4 vs. 69.6%, p < .05) of the thin and mediate groups were significantly lower than those in the thick group, whereas the ectopic pregnancy rate (11.5 and 1.9 vs. 0%, p < .05) was significantly higher in the thin group than in the mediate and thick group. Multivariate logistic regression analysis showed that age (OR = 0.956, 95% CI [0.931, 0.982], p < .05), number of embryos transferred (OR = 2.491, 95% CI [1.670, 3.715], p < .05) and endometrial thickness on the transplantation day (OR = 1.124, 95% CI [1.067, 1.185], p < .05) were independent factors significantly associated with clinical pregnancy. In conclusion, endometrial thickness (>14.69 mm) on the day of transfer, two cleavage embryos transferred, and female age (≤33.5 years) are independent factors affecting clinical pregnancy outcomes in controlled ovarian hyperstimulation with GnRH-a long protocol for assisted conception. IMPACT STATEMENT What is already known on this subject? Fresh embryo transfer cycle with GnRH-a long protocol will result in a higher pregnancy rate in controlled ovarian hyperstimulation cycles. What do the results of this study add? Endometrial thickness on the day of transfer, number of embryos transferred, and female age were independent factors affecting clinical pregnancy outcomes. What are the implications of these findings for clinical practice and/or further research? When performing a fresh IVF/ICSI embryo transfer cycle with GnRH-a long protocol for ovulation induction, the independent affecting factors should be taken into consideration.

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.