Ovarian Hyperstimulation Syndrome Rate Research Articles

P-680 Comparison of ovarian hyperstimulation syndrome (OHSS) rates resulting from conventional dosing versus personalized dosing of follitropin delta in ovarian stimulation, analysis of RITA, ESTHER-1 trials

Abstract Study question To compare OHSS rates with conventional dosage of follitropin delta in the RITA-1 and RITA-2 trials (hereafter ‘RITA’) to personalized dosing in the ESTHER-1 trial. Summary answer RITA and ESTHER-1 had similar efficacy and OHSS rates despite differences in dosing regimens, possibly due to differences in fresh transfer cancellation rates. What is known already Follitropin delta is a human cell-line derived follicle stimulating hormone whose fixed dosage in ovarian stimulation, personalized based upon body weight and serum anti-Müllerian hormone (AMH) and body weight, has been shown to be safe and effective in Gonadotrophin Releasing Hormone (GnRH) antagonist ovarian stimulation protocols. In the present trial, conventional dosing of follitropin delta allowing for dose revisions has been evaluated in GnRH antagonist ovarian stimulation protocols to demonstrate the broad utility of this gonadotrophin therapeutic and to address United States (US) regulatory considerations. Study design, size, duration RITA were randomized, double-blind, controlled, US multicentre trials of follitropin delta. The primary endpoint was cumulative ongoing pregnancy rate after fresh/frozen transfers within 12 months of cycle start. 1058 women 18-42 years randomized 10:1 to follitropin delta or placebo. ESTHER-1 was a randomized, European multicentre, assessor-blind, noninferiority trial of follitropin delta. The primary endpoints were fresh transfer ongoing pregnancy and implantation rates. 1329 women 18-40 years randomized 1:1 to follitropin delta or follitropin alfa. Participants/materials, setting, methods In RITA, 12 µg/day, 15 µg/day dosages were used for 4 days: 18-34 or 35-42 years, respectively, with 3 µg dose adjustments thereafter depending on response. Human chorionic gonadotropin (hCG) was used if < 20 follicles of ≥ 12 mm and estradiol level <3,000 pg/mL. Else, agonist trigger and fresh transfer cancellation; ≥20 oocytes retrieved also cancelled fresh transfer. In ESTHER-1, hCG was used if < 25 follicles of ≥ 12 mm. Else, agonist trigger, and fresh transfer cancellation. Main results and the role of chance The ongoing pregnancy rate per fresh transfer with follitropin delta was 41.9% in RITA and 36.3% in ESTHER-1. The primary efficacy endpoint was met for all 3 trials. Rates and severity defined by Golan criteria of OHSS observed in RITA and ESTHER-1 were similar, respectively for: all OHSS, any grade (3.1% versus 3.5%), Grade 1 (0.3% versus 0.5%), Grade 2 (0.8% versus 0.9%), Grade 3 (1.8% versus 1.1%), Grade 4 (0.2% versus 0.6%), and Grade 5 (0.1% versus 0.5%). The rate of early OHSS, defined as onset ≤9 days after trigger of final follicular maturation, was also similar, respectively for any grade (2.2% versus 2.6%), Grade 1 (0.3% versus 0.3%), Grade 2 (0.6% versus 0.9%), Grade 3 (1.1% versus 0.8%), Grade 4 (0.1% versus 0.3%) and Grade 5 (0.1 % versus 0.3%). However, the fresh transfer cancellation rate was >3x higher in RITA (35.2%) than in ESTHER-1 (11.1%). Limitations, reasons for caution Other reasons for transfer cancellation in all trials included adverse events or no blastocyst available for transfer; however, no significant differences were observed. A placebo comparator was selected for RITA to meet regulatory requirements for double-blinding; women with ≤3 oocytes retrieved were offered support for treatment outside of the trials. Wider implications of the findings Stimulation with follitropin delta is effective and associated with low rates of OHSS when used with either conventional or personalized dosing. However, stricter criteria for the use of hCG as trigger and allowance of fresh transfer may be required with conventional dosing to maintain this safety profile. Trial registration number NCT01956110, NCT03740737, NCT03738618

P-655 Live birth rate in the fresh cycle associated with number of oocytes in ovarian stimulation with individualised follitropin delta: an individual patient data meta-analysis

Abstract Study question What is the optimum number of oocytes retrieved to achieve a live birth for women undergoing ovarian stimulation with individualised follitropin delta? Summary answer The live birth rate (LBR) in the fresh cycle was highest in the range of 8-14 oocytes retrieved, peaking at 11 oocytes. What is known already The number of oocytes retrieved following ovarian stimulation for assisted reproductive technologies is regarded a prognostic marker of pregnancy outcome, where high numbers increase chances of live birth but also the risk of complications, especially ovarian hyperstimulation syndrome (OHSS). Thus, an optimum range of oocytes retrieved is essential. Still, there is no consensus regarding this range in fresh cycles. Optimum numbers between 6 and 15 oocytes have been suggested, taking the risk of OHSS into consideration. The individualised dosing algorithm for the recombinant follicle-stimulating hormone follitropin delta has a target range of 8–14 oocytes. Study design, size, duration Individual patient data meta-analysis of 1772 patients from 5 randomised controlled trials using individualised dosing of follitropin delta for ovarian stimulation, with fixed daily dosing based on serum anti-Müllerian hormone (AMH) and body weight. The analysis included patients with ≥1 oocyte retrieved. Outcomes of LBR and OHSS in the fresh stimulation cycle were evaluated in relation to number of oocytes retrieved. Subgroup analyses were performed based on age, AMH and number of oocytes retrieved. Participants/materials, setting, methods Participants were women, 18–42 years, undergoing first or second in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycle in a GnRH antagonist/long agonist protocol with human chorionic gonadotrophin or GnRH agonist triggering and IVF/ICSI. Single or double embryo/blastocyst transfer was performed on Day 3/5. All pregnancies were followed until birth. Predicted live birth was obtained using a logistic regression analysis with fractional polynomials to assess the association between number of oocytes retrieved and live birth. Main results and the role of chance The studied population (n = 1772) had a mean age of 32.6 years and median AMH of 17.7 pmol/l. Mean number of oocytes retrieved was 10.4, the LBR was 32.1% and the OHSS rate (any grade and onset) was 6.6%. The LBR steadily increased with the number of oocytes retrieved up to a plateau starting at 8 oocytes, with a LBR above 34% in the range of 8-14 oocytes retrieved, peaking at 34.9% for 11 oocytes. Beyond 14 oocytes, LBR gradually declined. By number of oocytes (grouped), the LBR was 27.8%, 33.6% and 30.9% at 1-7, 8-14 and ≥15 oocytes. In patients with embryo transfer, corresponding rates were 32.8%, 37.2% and 38.7%. In the subgroup analyses, LBR decreased with increasing age (32.7%, 30.7% and 23.4% at < 35, 35-37 and 38-42 years) while it was similar for AMH <15 and ≥15 pmol/l (30.4% and 31.3%, respectively). LBR was highest at 8-14 oocytes in patients <35 years (28.0%, 36.2% and 32.4% at 1-7, 8-14 and ≥15 oocytes), while it was consistently low (<26%) in patients 38-42 years, irrespective of number of oocytes retrieved. The OHSS rate (any grade) increased from 2.1% with 1-7 oocytes, to 5.2% with 8-14 oocytes and 17.0% with ≥15 oocytes. Limitations, reasons for caution A limitation of this study is the small number of patients with >20 oocytes retrieved in the studied population. Wider implications of the findings The current individual patient data meta-analysis suggests an optimum range of 8-14 oocytes retrieved to achieve a live birth in fresh cycles with follitropin delta. Furthermore, the analysis demonstrates a marked increase in OHSS rate from 15 oocytes retrieved. The results support the appropriateness of individualised follitropin delta dosing regimen. Trial registration number NCT01956110, NCT03228680, NCT03296527, NCT03564509, NCT03809429

P-715 outcomes of in vitro fertilization and embryo transfer among ethnic Tibetan, Yi and Han Chinese women

Abstract Study question Does difference exist in the outcomes of in vitro fertilization and embryo transfer (IVF-ET) among ethnic Tibetan, Yi and Han Chinese women? Summary answer We report that the outcomes of IVF-ET were poorer among ethnic Yi women compared with ethnic Han and Tibetan women. What is known already It has been reported that the outcomes of IVF-ET are correlated with ethnicity/race in Europe and the United States as an independent factor. Sichuan is the only province in China where all 56 ethnic groups reside, with ethnic Han, Yi and Tibetan Chinese having the highest proportions. In Chengdu city (the capital of Sichuan province, basin), the majority ethnic group is Han, whilst in Liangshan and Aba Prefectures (plateau), the major ethnic groups are Yis and Tibetans. The living environment, diet, custom, medical condition and genetic backgrounds are different among different ethnic groups. Study design, size, duration In this multi-center retrospective cohort study, a total of 58374 Chines women aged 20 ∼ 45 had undergoing the first IVF or intracytoplasmic sperm injection (ICSI) ET treatment cycle with non-donor gametes from January 2014 to December 2022 were enrolled. Participants/materials, setting, methods The patients were enrolled from two University Affiliated Hospitals and one Reproductive Hospital in Chengdu. The controlled ovarian stimulation protocols were gonadotropin releasing hormone (GnRH) agonist protocol or GnRH antagonist protocol. The patients were divided into three groups based on their ethnic origins: Tibetans (n = 1069), Yis (n = 2273) and Hans (n = 55032). The outcomes of IVF-ET were compared, with the primary outcome being the live birth rate. Main results and the role of chance The proportion of GnRH agonist protocol and IVF fertilization, the rates of moderate and severe ovarian hyper-stimulation syndrome (OHSS), and cleavage embryo formation in ethnic Han women were significantly higher than in the ethnic Yis and Tibetans (P < 0.05). The rates of implantation, clinical pregnancy and live birth (35.5% vs. 42.4%) were significantly lower, whereas the late abortion rate was significantly higher in Yi women than that in Han women (P < 0.05). The live birth rate was significantly lower in Yi women (35.5%) than in Tibetan (43.3%) and Han women (42.2%) (P < 0.05). Adjustment was made for age, duration, type and etiology of infertility, history of spontaneous abortion, smoking, alcohol, tuberculosis infection, body mass index, antral follicle count, antimüllerian hormone, and so on, by multivariate logistic regression analysis. Yi women had significantly lower rates of moderate and severe OHSS (OR = 0.69, 95% CI = 0.49-0.94, P = 0.024) and clinical pregnancy (OR 0.8, 95% CI 0.70-0.93, P = 0.002) compared with ethnic Hans. Yi women had significantly lower live birth rate compared with ethnic Hans (OR = 0.79, 95% CI = 0.68-0.92, P = 0.002) and Tibetans (OR 0.73, 95% CI 0.58-0.92, P = 0.007). Limitations, reasons for caution The limitations are related with the retrospective study and lack of some demographic characteristics of the patients which may influence the outcomes of IVF-ET, including diet habits, educational level, and economic status. Wider implications of the findings The ethnic group is an independent factor for the outcomes of IVF-ET among ethnic Tibetan, Yi and Han women. Among the three ethnic groups, the Yis had lower live birth rate and moderate and severe OHSS, whilst ethnic Han women had more moderate and severe OHSS. Trial registration number ChiCTR2300070269

P-729 Contribution of medical-administrative databases to health monitoring: example of ovarian hyperstimulation syndrome (OHSS)

Abstract Study question Can we monitor post-oocyte retrieval ovarian hyperstimulation syndrome (OHSS) in the French national health data system to complement the French ART vigilance system? Summary answer Medico-administrative databases offer a more comprehensive view of post-oocyte retrieval complications and can be used to detect abnormal increases in frequency and outlier ART centers. What is known already Assisted reproductive technology (ART), widely used in Europe, accounts for about 3% of births in France. The various studies of ART complications are reassuring, showing relatively low overall complication rates. Nonetheless, the European Union has established a vigilance system to monitor these complications. However, this system is not an exhaustive source of information and does not provide a complete overview of post-ART complications. Study design, size, duration The study population was identified from the comprehensive French National Hospital discharge database and included 53,490 women under 46 years old who underwent 65,924 oocyte retrievals in 2022. Women were classified into three population subgroups according to the indication of oocyte retrieval: infertility (IF), fertility preservation (FP), and oocyte donation (OD). Participants/materials, setting, methods Hospital stays for OHSS within two months post-retrieval were analyzed and characterized according to various characteristics (age, comorbidities, indication of oocyte retrieval, type of hospital stay, length of hospital stay...). Multivariate analysis was performed to determine the relation between the occurrence of OHSS and women’s characteristics, and results are expressed as odds ratios (ORs) and 95% CI. A funnel plot was used to compare the OHSS rate per center with the national average. Main results and the role of chance Hospitalized OHSS accounted for 1.1% of retrievals in 2022 (n = 718). The mean age of the women was 31.6 years (SD 4.5). Women with Polycystic Ovary Syndrome (PCOS) accounted for about 4% of the women with OHSS. More than half of OHSS hospital stays lasted less than two days (54%). Of these stays, 2% of women were in intensive care. Multivariate analysis showed a significantly higher OHSS risk in women under 30 and those with PCOS. Other risk factors are currently introduced into the model, such as a history of OHSS or pregnancy. Funnel plot analysis showed that one ART center has an OHSS rate significantly higher than the national average. In the centers that stand out from all the others, the objective is to return to these centers to understand the possible reasons for this observed rate and to implement corrective measures. Limitations, reasons for caution Despite all its advantages, the French national health data system presents some limitations, such as the risk of inappropriate coding. Moreover, the unavailability of personal or clinical information prevented us from considering certain risk factors. Wider implications of the findings Despite the limits of using medico-administrative databases, this approach provides a better representation of post-ART complications and is a promising way to complement the ART vigilance reporting system. This concept will also be generalized to other complications with regular feedback to professionals. Trial registration number not applicable

P-605 Effectiveness of follitropin delta in patients with potential poor response: A post hoc analysis from the ESTHER-1 trial

Abstract Study question What is the effectiveness of individualised follitropin delta dosing compared to conventional follitropin alfa dosing in patients with potential poor response undergoing ovarian stimulation? Summary answer Individualised follitropin delta dosing provides a favourable efficacy and safety balance and is as good as follitropin alfa in patients with potential poor ovarian response. What is known already Poor ovarian response to controlled ovarian stimulation constitutes a challenge in in-vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) treatment. The dosing algorithm of follitropin delta incorporates the prediction of ovarian response based on anti-Müllerian hormone (AMH), an accurate marker of ovarian reserve, and body weight, for an individualised dosing. In the general IVF/ICSI population and potential high responders, individualised follitropin delta reduces the risk of ovarian hyperstimulation syndrome (OHSS) and/or preventive interventions for OHSS, with sustained efficacy compared to conventional follitropin alfa. However, the performance of follitropin delta in the subpopulation of patients with potential poor response has not been evaluated. Study design, size, duration Post hoc analysis of 332 patients with potential poor response from the ESTHER-1 trial (determined by AMH level at screening <9 pmol/L). Patients received the maximum daily dose of 12 µg follitropin delta (fixed dosing throughout stimulation) as stipulated by the dosing algorithm for patients with AMH <15 pmol/l, or follitropin alfa at a starting dose of 150 IU, with potential dose adjustments from stimulation day 6 and onwards (maximum daily dose of 450 IU). Participants/materials, setting, methods Participants were women, 18–40 years, undergoing their first IVF/ICSI cycle in a GnRH antagonist protocol, including triggering with human chorionic gonadotrophin, IVF/ICSI insemination, and single or double blastocyst transfer on Day 5. Ultrasound was performed 10–11 weeks after transfer to confirm ongoing pregnancy. All pregnancies were followed until birth. Study outcomes include number of oocytes retrieved and number of good quality blastocysts, ongoing pregnancy and live birth rates, cycle cancellation and OHSS rates. Main results and the role of chance A total of 332 patients (25.0% of the overall ESTHER-1 population) had serum AMH at screening of < 9 pmol/l and were included in the analysis: 168 were treated with follitropin delta and 164 were treated with follitropin alfa. Baseline characteristics were similar between the treatment groups, with a mean age of 34.8 years, a median AMH of 5.7 pmol/l and a mean weight of 64.5 kg. With follitropin delta, the mean daily dose was 12.0 µg and with follitropin alfa 12.4 µg, resulting in mean total doses of 104.6 µg and 112.3 µg, respectively. The mean number of oocytes retrieved was 5.8 ± 3.5 with follitropin delta and 5.5 ± 3.6 with follitropin alfa and the mean number of good-quality blastocysts was 1.2 ± 1.4 with both treatments. The ongoing pregnancy rate was 29.8% with follitropin delta and 29.3% with follitropin alfa and the live birth rates were 29.2% and 28.7%, respectively. Thirteen patients (7.7%) treated with follitropin delta and 14 (8.5%) treated with follitropin alfa had their cycles cancelled due to poor response. One case of OHSS (0.6%) was observed in the follitropin delta group, and 3 cases (1.8%) were observed in the follitropin alfa group. Limitations, reasons for caution The main limitation of the study is its post hoc nature. Furthermore, the study is based on a relatively small number of patients. Wider implications of the findings This subgroup analysis, alongside the normoresponder and the potential hyperresponder subgroup of the ESTHER-1 trial, adds evidence for the effectiveness of follitropin delta across all ovarian reserve subgroups of the infertile population. Trial registration number NCT01956110

P-639 Are GnRH-agonists (GnRH-a) safer and more effective ovulation triggers than human chorionic gonadotrophin (hCG)? A retrospective analysis of frozen embryo replacement cycle (FERC) outcomes

Abstract Study question Are GnRH-agonists (GnRH-a) safer and more effective ovulation triggers than human chorionic gonadotrophin (hCG)? A retrospective analysis of frozen embryo replacement cycle (FERC) outcomes Summary answer GnRH-a trigger reduces the incidence and severity of ovarian hyperstimulation syndrome (OHSS) leading to significantly improved clinical outcomes when compared to hCG trigger for FERCs. What is known already Ovulation induction plays a crucial role in the success and safety of ART cycles. hCG is extensively used as an alternative to LH to trigger ovulation. However, high levels of sustained hCG exposure increases the risk of OHSS, a potentially life-threatening complication of ART. To eliminate the risk and incidence of OHSS, GnRH-a can be used to trigger ovulation. Although there are concerns regarding clinical outcomes with fresh transfers following GnRH-a trigger, it elicits a more physiological response compared to hCG. This may lead to improved embryo quality, utilisation, and better clinical outcomes following a freeze-all strategy, reducing patients’ time-to-pregnancy. Study design, size, duration This was a retrospective data analysis of FERC outcomes following fresh IVF or ICSI cycles, involving ovulation induction using either hCG or GnRH-a as a final trigger. The evaluation included results from cycles spanning an eight-year period, from January 2012 to December 2019 at Hammersmith Hospital London. A total of 160 cycles were included in the study, with 76 in the hCG trigger group and 84 in the GnRH-a trigger group. Participants/materials, setting, methods Strict inclusion criteria were employed to render the study groups as comparable as possible and to minimise the effect of independent variables, such as oocyte and sperm factors, on oocyte or embryo developmental competence. Inclusion criteria: women ≤37 years old at the start of treatment, GnRH antagonist stimulation, blastocyst vitrification-warming and transfers only. Statistical significance was calculated using independent t-test and Fisher’s Chi-square exact test. Main results and the role of chance The mean age (±SD) of patients at the time of oocyte retrieval was comparable across groups. The average number of oocytes collected were significantly higher in the GnRH-a group compared to hCG (28.31 vs. 18.07, respectively, P < 0.001). Embryological data (maturation, fertilisation, blastocyst formation, blastocyst utilisation and good quality blastocyst formation rates) were comparable across both groups. OHSS rate was significantly lower in the GnRH-a group (17% vs. 50%. P < 0.0001). The following clinical data were significantly higher (P < 0.05) in the GnRH-a group compared to hCG: implantation rate (56% vs. 36%), clinical pregnancy rate (56% vs. 36%) and live birth rate (42% vs. 27%). Limitations, reasons for caution The biggest limitation of this study is its retrospective nature and the application of various inclusion-exclusion criteria that have resulted in relatively small sample sizes. Additionally, numerous other confounders, e.g. patient body mass index, cause/duration of infertility and stimulation duration, have not been considered in this study. Wider implications of the findings The findings of this study are promising and demonstrate a great potential for benefit in the use of GnRH-a trigger with a freeze-all strategy to minimise the risk of OHSS, diminishing the associated patient morbidity and mortality, reducing healthcare costs, improving clinical outcomes, and reducing the overall time-to-pregnancy for patients. Trial registration number not applicable

O-302 Feasibility and efficacy of a flexible and simplified ovarian stimulation protocol for oocyte donors, combining random-start corifollitropin alpha and progestin primed ovarian stimulation protocol (PPOS)

Abstract Study question Is the total number of retrieved oocytes in donors equivalent, according to the onset phase of stimulation with corifollitropin alpha in a random-start PPOS protocol? Summary answer The total number of retrieved and mature oocytes were not different after starting stimulation in the early, mid or late follicular or luteal phases. What is known already Recent studies have shown the ability to obtain oocytes of equivalent quality after follicular or luteal phase ovarian stimulation and have also demonstrated the efficacy and safety of the PPOS protocol in oocytes donors. In order to provide a more friendly, simplified and flexible ovarian stimulation protocol reducing the burden for donors, we studied the impact on oocyte yield of combining a random start corifollitropin alpha stimulation with the concomitant prevention of premature LH surge by progestin administration. Study design, size, duration This multicenter open-labelled RCT was performed in 4 oocytes donation centers from July 2020 to September 2023 to assess the equivalence in terms of number of retrieved oocytes of a delayed onset of corifollitropin alpha stimulation with concomitant administration of desogestrel in Mid Follicular Phase (MFP/D4-D7 of the natural cycle), Late Follicular Phase (LFP/D8-D11), Ovulatory Phase (OP/D12-D15) or Luteal Phase (LP/D16-D30) compared to the standard start in Early Follicular Phase (EFP/D1-D3). Participants/materials, setting, methods From 110 randomized oocyte donors,102 reached triggering of ovulation with triptoreline acetate and OPU : EFP n = 22, MFP n = 20, LFP n = 19, OP n = 18 and LP n = 23. The sample size was calculated to show an equivalence between groups in total number of retrieved oocytes. Secondary endpoints were the number of mature oocytes, premature LH surge and Ovarian Hyperstimulation Syndrome rates. Differences were tested using a ANOVA test or a Pearson’s Chi2 test, as appropriate. Main results and the role of chance Donors were 33 [29.2-35.0] years old [95% Confidence interval] with a mean BMI of 23.4 [21.1-26.3] kg/m2. The mean number (SD) of retrieved oocytes was 14.2 (9.1). In intention to treat analysis, there was no significant difference between the 5 groups, regarding the total number of retrieved oocytes. The mean numbers of retrieved oocytes from the 5 groups were 12.5 (7.7), 13.2 (8.0), 15.7(9.8), 17.8 (11.4), and 12.8(8.3), respectively in the EPF group, the MPF group, the LPF group, the OP group and the FP group, with no significant differences between the groups (p = 0.30). The mean (SD) number of mature oocytes was 11.8 (7.6) with no significant differences between the 5 groups. Only one premature LH surge was reported in the MFP group (0.98%). Four minor to moderate OHSS were reported (3.9%). Limitations, reasons for caution The main limitation of our study is the small sample size responsible for a lack of power. But to our knowledge, this is the first RCT to compare the number of oocytes retrieved, according to the onset phase of ovarian stimulation in a random-start PPOS protocol, for oocyte donors. Wider implications of the findings The proportion of ovarian stimulation cycles with freeze-all is constantly increasing worldwide. Therefore simplified, ultra-flexible ovarian stimulation protocols could be proposed to maintain the spread of the workload along the working days without programming, with fewer injections and reduced burden for patients, with the same efficacy. Trial registration number NCT03895099

A Comparative Study of Fresh versus Frozen Embryo Transfer and their Outcomes in Patients with Polycystic Ovarian Syndrome

Background: In in vitro fertilization (IVF)/assisted reproductive technology, fresh embryo transfer is generally preferred over frozen embryo transfer (FET). Still, some research shows that FET could increase the childbirth rate which reduces the amount of ovarian hyperstimulation syndrome (OHSS) and pregnancy problems in females with polycystic ovarian syndrome (PCOS). There is a high risk of aberrant pregnancies, incorrect placentation, and other issues when a fresh embryo is transferred. They are more likely to get OHSS. Fresh embryo transfer reduces the chances to get pregnant as the stimulatory effect will be there for long time, and the endometrium is less receptive for the embryos and vice versa in the case of FET. For IVF, the transfer of fresh embryos is typically preferred over the transfer of frozen embryos. However, some research suggests that the transfer of frozen embryos may increase the live birth rate and decrease the rates of OHSS and pregnancy complications in women with polycystic ovary syndrome. One of the most prevalent endocrine illnesses in women of reproductive age is PCOS. Chronic anovulation, hyperandrogenemia, and clinical signs of hyperandrogenism are hallmarks of polycystic ovary syndrome in the absence of additional diseases such as congenital adrenal hyperplasia, androgen-producing tumors, or Cushing syndrome. Despite the fact that some patients are discovered to be clomiphene citrate (CC) resistant, CC is still the first line of treatment for anovulatory infertility caused by PCOS. Numerous treatments, such as the usage of metformin, ovarian drilling, and gonadotropin therapy, may be taken into consideration in these people. Materials and Methods: Fifty women in all ranging in age from 25 to 45 participated in the study. Half of the study participants are from Wardha, and the other half are from rural areas close to Wardha. Participants were chosen from patients who sought medical attention for issues relating to infertility. We have taken consent from all the patients with the mutual understanding that their medical is being used for a comparative study. All the patients in our study are subjected to IVF following embryo transfer. We have taken n = 50 in which all the patients are PCOS patients with AMH noticeably higher than others. Out of them, we have taken 25 patients who are allocated for fresh Day 5 transfer and 25 of them are allocated for Day 5 FET. We have collected data for a total of 50 patients and compared the β-human chorionic gonadotropin values whether it is positive or negative in each case. We have done a comparative study by comparing the results of patients undergoing fresh versus FET with their ages ranging from 25 to 45 years. Results: The data of fresh Day 5 embryo and frozen Day 5 transfer and their outcome were noted. We concluded that FET has good results compared to fresh embryo transfer.

A Comparative Study of Fresh versus Frozen Embryo Transfer and their Outcomes in Patients with Polycystic Ovarian Syndrome

Background: In in vitro fertilization (IVF)/assisted reproductive technology, fresh embryo transfer is generally preferred over frozen embryo transfer (FET). Still, some research shows that FET could increase the childbirth rate which reduces the amount of ovarian hyperstimulation syndrome (OHSS) and pregnancy problems in females with polycystic ovarian syndrome (PCOS). There is a high risk of aberrant pregnancies, incorrect placentation, and other issues when a fresh embryo is transferred. They are more likely to get OHSS. Fresh embryo transfer reduces the chances to get pregnant as the stimulatory effect will be there for long time, and the endometrium is less receptive for the embryos and vice versa in the case of FET. For IVF, the transfer of fresh embryos is typically preferred over the transfer of frozen embryos. However, some research suggests that the transfer of frozen embryos may increase the live birth rate and decrease the rates of OHSS and pregnancy complications in women with polycystic ovary syndrome. One of the most prevalent endocrine illnesses in women of reproductive age is PCOS. Chronic anovulation, hyperandrogenemia, and clinical signs of hyperandrogenism are hallmarks of polycystic ovary syndrome in the absence of additional diseases such as congenital adrenal hyperplasia, androgen-producing tumors, or Cushing syndrome. Despite the fact that some patients are discovered to be clomiphene citrate (CC) resistant, CC is still the first line of treatment for anovulatory infertility caused by PCOS. Numerous treatments, such as the usage of metformin, ovarian drilling, and gonadotropin therapy, may be taken into consideration in these people. Materials and Methods: Fifty women in all ranging in age from 25 to 45 participated in the study. Half of the study participants are from Wardha, and the other half are from rural areas close to Wardha. Participants were chosen from patients who sought medical attention for issues relating to infertility. We have taken consent from all the patients with the mutual understanding that their medical is being used for a comparative study. All the patients in our study are subjected to IVF following embryo transfer. We have taken n = 50 in which all the patients are PCOS patients with AMH noticeably higher than others. Out of them, we have taken 25 patients who are allocated for fresh Day 5 transfer and 25 of them are allocated for Day 5 FET. We have collected data for a total of 50 patients and compared the β-human chorionic gonadotropin values whether it is positive or negative in each case. We have done a comparative study by comparing the results of patients undergoing fresh versus FET with their ages ranging from 25 to 45 years. Results: The data of fresh Day 5 embryo and frozen Day 5 transfer and their outcome were noted. We concluded that FET has good results compared to fresh embryo transfer.

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

The effect of laparoscopic ovarian drilling on pregnancy outcomes in polycystic ovary syndrome women with more than 2 in-vitro fertilization cycle failures: A pilot RCT.

Background: The effect of laparoscopic ovarian drilling (LOD) before in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI) cycles on pregnancy outcomes is an unclear and challenging subject. Objective: To evaluate the impact of LOD before IVF/ICSI cycles on controlled ovarian stimulation and pregnancy outcomes in polycystic ovary syndrome (PCOS) women with a history of more than 2 IVF failures. Materials and Methods: In this randomized clinical trial, women with PCOS diagnosis who referred to Arash Women's hospital, Tehran, Iran for IVF/ICSI cycle from August 2015-January 2018 were evaluated. Eligible participants were allocated into 2 groups randomly (n = 17/each group). The participants in the LOD group (intervention) were treated with laparoscopic couture, and after one month, they underwent IVF/ICSI cycles using the gonadotropin-releasing hormone antagonist protocol. The control group had no intervention. The oocyte and embryo qualities, ovarian hyperstimulation syndrome rate, the rates of chemical and clinical pregnancy and early miscarriage, live birth, and pregnancy complications, were compared between groups. Results: Finally, 34 participants were evaluated. The controlled ovarian stimulation outcomes were similar between groups. The ovarian hyperstimulation syndrome rate in the LOD group was significantly lower than in the control group (p = 0.04). One case of spontaneous pregnancy was reported in the LOD group. No significant difference was observed between groups in clinical pregnancy, miscarriage, and live birth rates. The rates of pregnancy complications (gestational diabetes mellitus, preeclampsia, and preterm birth) were similar between groups. Conclusion: Performing LOD before IVF/ICSI cycles did not improve the pregnancy outcomes in PCOS women, a clinical trial with a larger sample size is needed to prove these results.

Live Birth Outcomes for PCOS Patients Under the Follicular-Phase Long-Acting GnRH Agonist Protocol or Antagonist Protocol - A Retrospective Chinese Cohort.

For patients with polycystic ovary syndrome (PCOS) to undergo in vitro fertilization (IVF) and embryo transfer (ET), there has been no consensus regarding which protocol is the most optimal for live birth rate in fresh cycles. We sought to evaluate depot gonadotropin-releasing hormone (GnRH) agonist protocol versus GnRH antagonist protocol in IVF outcomes for PCOS patients in a single fertility center. In this retrospective cohort, PCOS patients who visited the Second Hospital of Hebei Medical University reproductive center between February 2012 and December 2019 were screened, and 533 PCOS infertility patients were included undergoing their first IVF cycle, with 470 in the depot GnRH agonist group and 63 in the GnRH antagonist group. The primary of this study outcome was the fresh live birth rate (LBR). PCOS women in the depot GnRH agonist group had a higher LBR (49.79%) than those in the GnRH antagonist group (34.92%, p = 0.027). The multivariable logistic regression also confirmed that women in the depot GnRH agonist group had a higher LBR than those in the GnRH antagonist group (OR = 1.83, 95% CI 1.05~3.18, p = 0.032). After propensity score matching (PSM), the LBR in the depot GnRH agonist group was higher (50.32%) than that of the GnRH antagonist group (35.48%), p = 0.033. The ovarian hyperstimulation syndrome (OHSS) rates were similar between the two groups, with 35 in the depot GnRH group and 6 in the GnRH antagonist group (p = 0.561). For PCOS patients in fresh embryo transfer cycles, the depot GnRH agonist protocol may lead to a higher LBR than the antagonist protocol with satisfied lower OHSS rates.

Highly Purified Human Menopausal Gonadotropin (HP-hMG) Versus Recombinant Follicle-Stimulating Hormone (rFSH) for Controlled Ovarian Stimulation in USPredicted High-Responder Patients: A Cost-Comparison Analysis.

Infertility imposes considerable clinical and economic burden, and the high costs of fertility care are a major barrier to payers. This study assessed the cost differences of highly purified human menopausal gonadotropin (HP-hMG) versus recombinant follicle stimulating hormone (rFSH) for controlled ovarian stimulation (COS) protocols in predicted high-responders from the US payer perspective. A discrete event simulation model was built to perform a cost-comparison analysis of HP-hMG versus rFSH in a cohort of predicted high-responders undergoing up to three embryo transfer cycles, informed by efficacy data from the MEGASET-HR trial. The model considered an event-based treatment pathway and transition probabilities were derived from MEGASET-HR. A variable time horizon was employed, and deterministic and probabilistic sensitivity analyses conducted. Subjects undergoing COS with HP-hMG and rFSH demonstrated comparable live birth rates following three in vitro fertilization (IVF) cycles, with 161 live births with HP-hMG and 152 live births with rFSH, per 310 high-responders. The total cost saving per live birth in subjects receiving HP-hMG versus rFSH was US$3024. These cost savings were largely driven by the need for fewer embryo transfers to achieve similar efficacy outcomes and a reduced rate of ovarian hyperstimulation syndrome. Following deterministic sensitivity analysis, HP-hMG remained cost saving in all baseline parameter variations. No parameters led to rFSH providing cost savings when compared with HP-hMG. Comparable clinical outcomes can be achieved at a lower cost when using HP-hMG versus rFSH based COS protocols in a cohort of predicted high-responders. Such cost savings may reduce the economic burden infertility currently presents to US healthcare providers and those seeking fertility care.

Guideline No. 315: Prevention of Ovarian Hyperstimulation Syndrome

Summary Statements1.The particular follicle-stimulating hormone formulation used for ovarian stimulation does not affect the incidence of ovarian hyperstimulation syndrome. (I)2.Coasting may reduce the incidence of severe ovarian hyperstimulation syndrome. (III)3.Coasting for longer than 3 days reduces in vitro fertilization pregnancy rates. (II-2)4.The use of either luteinizing hormone or human chorionic gonadotropin for final oocyte maturation does not influence the incidence of ovarian hyperstimulation syndrome. (I)5.There is no clear published evidence that lowering the human chorionic gonadotropin dose will result in a decrease in the rate of ovarian hyperstimulation syndrome. (III)6.Cabergoline starting from the day of human chorionic gonadotropin reduces the incidence of ovarian hyperstimulation syndrome in patients at higher risk and does not appear to lower in vitro fertilization pregnancy rates. (II-2)7.Avoiding pregnancy by freezing all embryos will prevent severe prolonged ovarian hyperstimulation syndrome in patients at high risk. (II-2)8.Pregnancy rates are not affected when using gonadotropin-releasing hormone (GnRH) agonists in GnRH antagonist protocols for final egg maturation when embryos are frozen by vitrification for later transfer. (II-2) Recommendations1.The addition of metformin should be considered in patients with polycystic ovarian syndrome who are undergoing in vitro fertilization because it may reduce the incidence of ovarian hyperstimulation syndrome. (I-A)2.Gonadotropin dosing should be carefully individualized, taking into account the patient’s age, body mass, antral follicle count, and previous response to gonadotropins. (II-3B)3.Cycle cancellation before administration of human chorionic gonadatropin is an effective strategy for the prevention of ovarian hyperstimulation syndrome, but the emotional and financial burden it imposes on patients should be considered before the cycle is cancelled. (III-C)4.Gonadotropin-releasing hormone (GnRH) antagonist stimulation protocols are recommended in patients at high risk for ovarian hyperstimulation syndrome (OHSS). The risk of severe OHSS in patients on GnRH antagonist protocols who have a very robust ovarian stimulation response can be reduced by using a GnRH agonist as a substitute for human chorionic gonadotropin to trigger final oocyte maturation. (I-B)5.A gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist trigger for final oocyte maturation is recommended for donor oocyte and fertility preservation cycles. (III-C)6.Albumin or other plasma expanders at the time of egg retrieval are not recommended for the prevention of ovarian hyperstimulation syndrome. (I-E)7.Elective single embryo transfer is recommended in patients at high risk for ovarian hyperstimulation syndrome. (III-C)8.Progesterone, rather than human chorionic gonadotropin, should be used for luteal phase support. (I-A)9.Outpatient culdocentesis should be considered for the prevention of disease progression in severe ovarian hyperstimulation syndrome. (II-2B)

P-205 comparison of GnRH antagonist protocol versus progestin-primed protocol in high ovarian responders: a propensity score-matched study

Abstract Study question To compare the clinical outcomes and cost-efficiency between gonadotropin-releasing hormone (GnRH) antagonist and progestin-primed ovarian stimulation (PPOS) protocol in high ovarian responders. Summary answer Comparing with PPOS protocol, GnRH antagonist protocol was associated with shorter time to live birth, higher OHSS rate and less cost in high responders. What is known already For high ovarian responders prone to develop ovarian hyperstimulation syndrome (OHSS), the best option should be the GnRH antagonist, as it has been shown to significantly reduce the incidence of OHSS. By applying ovarian stimulation using the combination of antagonist with agonist trigger and embryos freezing, OHSS can be erased. PPOS protocol in combination with a freeze-all strategy has proved to be a valid alternative to the conventional stimulation protocols. Recent studies showed that comparing with antagonist protocol, a lower cumulative live birth rate (CLBR) was associated with PPOS in general population, with no data available in high responders. Study design, size, duration This was a propensity score-matched retrospective cohort study. From Jan. 2016 to Jan. 2023, 5810 patients with AMH > 3.67ng/ml undergoing IVF treatment with antagonist or PPOS protocol at the Sixth Affiliated Hospital of Sun Yat-sen University were screened. Participants/materials, setting, methods Two-to-one propensity score matching was performed with a caliper of 0.2. After matching, 540 patients in GnRH antagonist group and 270 patients in PPOS group were included. Generalized estimated equation regression was applied to evaluate the impact of independent variables on the CLBR. Main results and the role of chance No significant difference in baseline characteristics was found in two groups. The OHSS (moderate to severe) rate was significantly higher in the GnRH antagonist group than in the PPOS group (7% vs. 3%). The clinical pregnancy rate and live birth rate per transfer were comparable between the two groups. After excluding patients who didn't achieve live birth but had surplus embryos, the CLBR was comparable between the antagonist and PPOS group (67.4% vs. 61.0%; Risk ratio = 1.106; 95% confidence interval [CI], 0.973-1.256, P = 0.109), and the generalized estimated equation regression analysis also showed that protocol selection had no significant impact on CLBR. The average time to live birth (TTLB) in the antagonist group was significantly shorter than the PPOS group (11.45 months vs. 12.13 months, P < 0.05). Besides, the average cost in the antagonist group was about $4933, while it was about $5465 in the PPOS group. Limitations, reasons for caution Although we recruited a large sample size and the sophisticate statistical analysis method, this was a retrospective study with an intrinsic limitation, besides more patients in the PPOS group had surplus embryos than in the antagonist group (24.1% vs. 19.8%). Further prospective RCTs are required to confirm our findings. Wider implications of the findings For infertile patients with high ovarian reserve, the clinical outcomes were comparable between GnRH antagonist and PPOS group. The antagonist group was associated with a shorter TTLB and more cost-effective, while the PPOS was associated with a lower OHSS rate. Trial registration number Not Applicable

Absence d’amélioration du taux de naissance vivante après soutien de la phase lutéale par agoniste de la GnRH

ObjectivesTo evaluate the impact of adding a GnRH agonist (GnRH-a) in luteal phase support (LPS) on live birth rates in IVF/ICSI in antagonist protocols. MethodsIn total, 341 IVF/ICSI attempts are analyzed in this retrospective study. Patients were divided into two groups: A f: LPS with progesterone alone (179 attempts) between March 2019 and May 2020; B: LPS with progesterone and an injection of triptorelin (GnRH-a) 0.1mg 6 days after oocyte retrieval (162 attempts) between June 2020 and June 2021. The primary outcome was live birth rate. The secondary outcomes were miscarriage rate, pregnancy rate and ovarian hyperstimulation syndrome rate. ResultsThe baseline characteristic are identical between the two groups except the infertility duration (longer in the group B). There was no significant difference between the two groups in live birth rate (24.1% versus 21.2%), pregnancy rate (33.3% versus 28.1%), miscarriage rate (4.9% versus 3.4%) and no increase the SHSO rate. The multivariate regression analysis after adjustment for age, ovarian reserve and infertility duration did not reveal a significant difference in live birth rate between the two groups. ConclusionIn this study, the results showed no statistically significant association with the single injection of a GnRH-a in addition to progesterone on live birth rate in luteal phase support.

Soft ovarian stimulation protocol in polycystic ovary syndromes women inspired by gonadotropin stimulated intrauterine insemination cycles converted to rescue IVF: time to shift the focus “retrospective study”

BackgroundPolycystic ovary syndrome (PCOs) women usually exhibit a high luteinizing hormone (LH) and hypersensitivity to exogenous gonadotropins stimulation which is a tremendous risk to ovarian hyperstimulation syndrome (OHSS). Since the pathophysiology of PCOS is mysterious, an aetiological approach to the treatment is difficult and should be individually designed. These features affect the outcome of treatment including ovulation and success rate. Also, PCOS women who have difficulty conceiving, frequently experience substantial treatment burden, risk, and psychological distress. Recently, a renewed interest has emerged in patient-friendly, low-risk, and less costly IVF treatments. Our study proposed a new soft protocol in PCOS ovrian stimulation without prior pituitary desensitization followed by fresh embryo transfer. Patients and methods: a retrospective cohort study was conducted between January 2018 to December 2021, including 48 out of 325 women with PCOS who underwent gonadotropin-stimulated intrauterine insemination cycles but due to unexpectedly high response with risk of multiple pregnancies and OHSS, they had been shifted to a rescue IVF and fresh embryo transfer. The primary outcomes were biochemical pregnancy, implantation rate, clinical pregnancy, rate of miscarriage, OHSS, and multiple pregnancies. Secondary outcomes were the endocrinological profiles, gonadotropin dose, and duration of stimulation. This study aims to evaluate the outcomes in the conversion of high-response gonadotropin intrauterine insemination (IUI) cycles to “rescue” in vitro fertilization (IVF/fresh embryo transfer) regarding implantation rates, pregnancy rates, and ovarian hyperstimulation syndrome (OHSS).ResultsThis study used a low dose gonadotropin injections (2.1 ± 1.4) for an average duration of (9.1 ± 1.2) and showed a high success pregnancy rate: biochemical pregnancies (56.2%), implantation rate (50.2%), clinical pregnancy rate (49.9%), and miscarriage rate (8.5%). Multiple pregnancies occurred in (6.6%) and OHSS(4.4%) only in a mild form.ConclusionOur study revealed that ovarian stimulation without prior pituitary suppression in high responders was feasible to improve the implantation rate and alleviate profound OHSS without compromising the pregnancy outcomes. This encourages all fertility specialists to implement this new protocol with expected high responders as an alternative to the conventional cycle segmentation protocol: GnRH agonist-antagonist IVF/freeze-all strategy.

Ovarian Hyperstimulation Syndrome (OHSS) requiring Intensive Care Unit (ICU) admission between 1996-2020 in England, Wales, and Northern Ireland.

Ovarian Hyperstimulation Syndrome (OHSS) is a life-threatening iatrogenic complication of In vitro fertilisation (IVF). This study aimed to quantify rates of Ovarian Hyperstimulation Syndrome (OHSS) requiring intensive care unit (ICU) admission and assess whether trends have changed between 1996-2020 commensurate with the introduction of safer IVF practices. Data regarding Intensive Care Unit (ICU) admission across England, Wales and Northern Ireland was gathered retrospectively from the Intensive Care National Audit and Research Centre (ICNARC) database. 38,957 female patients aged between 18-55 years were admitted to ICU for OHSS or related conditions between 1996-2020. The primary outcome was the rate of OHSS requiring ICU admission expressed as a proportion of the number of fresh IVF cycles conducted in that year according to Human Fertility and Embryology Authority (HFEA) records. Baseline characteristics (for example, age, ethnicity, BMI), biochemical parameters (such as renal function, serum electrolytes), length of ICU stay and duration and need for organ support, were also compared between ICU patients with 'confirmed OHSS' and those 'without OHSS'. There were 238 cases of 'confirmed OHSS' requiring ICU admission recorded between 1996-2020. Rates of OHSS requiring ICU admission declined over the study period (P=0.006); the annual rate of severe OHSS requiring intensive care admission halved when comparing those occurring between 1996-2007 and 2008-2020 (OR=0.37, 95% CI 0.37-0.45; P<0.0001). Patients spent a mean of 3.5 days in the ICU, with 86.3% of patients with 'confirmed OHSS' requiring at least 2 days of higher level (i.e., level 2 or 3) care. Patients with 'confirmed OHSS' required a shorter duration of renal, advanced cardiovascular, and advanced respiratory support than patients 'without OHSS' (P<0.0001 for all comparisons). There was no significant difference in BMI or ethnicity between those with 'confirmed OHSS' and those 'without OHSS', however women with 'confirmed OHSS' were younger (34 versus 41 years old, p<0.0001). Although absolute rates of OHSS requiring ICU admission recorded in this study are likely to represent a significant underestimate of all clinically significant OHSS, rates of OHSS requiring ICU admission have decreased since 1996 in concordance with the introduction of modern IVF practices.

The impact of letrozole on oocyte quality in assisted reproductive technology (ART); a randomized double-blind clinical trial

Objective To examine the effect of letrozole on oocyte quality and pregnancy outcome in assisted reproductive technology (ART). Methods This double blind placebo controlled clinical trial was conducted in Vali-Asr Infertility Center. Infertile women candidate for IVF that underwent antagonist protocol were selected. Eligible women randomly allocated into treatment (letrozole/Let group) and control (placebo) group. Participants received letrozole 5 mg/day or placebo at the time of gonadotropin start until trigger day in the same manner. Number of oocyte retrieved, metaphase II oocyte number, high grade oocyte number (G1), high quality embryo, Chemical and clinical pregnancy rate and OHSS (ovarian hyperstimulation syndrome) rate was recorded. 216 infertile women (104 in letrozole and 112 in the control group) were evaluated. Results In the Let group estradiol level was significantly lower (p_value < .001) and testosterone significantly higher than in the control group (p_value = .02). The number of retrieved oocytes, MII oocytes, G1 oocytes, and 2PN was significantly lower in the Let group (p < .05). No significant difference was found in the day of stimulation, total gonadotropin dose, OHSS rate, and clinical pregnancy rate between the two groups (p > 0.05). Conclusions According to the results, letrozole may reduce oocyte quality and cause poor IVF outcomes as well.

Extending letrozole treatment duration is effective in inducing ovulation in women with polycystic ovary syndrome and letrozole resistance

To evaluate whether extending letrozole (LE) treatment duration could induce ovulation in women with polycystic ovary syndrome (PCOS) who previously failed to ovulate after a 5-day regimen of 5 mg LE daily for at least 1 ovulation induction cycle, defined as "LE resistance". Retrospective cohort study. Tertiary care academic medical center. A total of 69 women with PCOS and LE resistance were included. The duration of LE treatment was increased in a stepwise manner (named as "2-step extended LE regimen"): a 7-day regimen of 5 mg LE daily was prescribed in the first ovulation induction cycle, and if ovulation did not occur, a 10-day regimen was prescribed in the subsequent cycle. Ovulation rate was the primary outcome. Clinical pregnancy rate, live birth rate, spontaneous ovulation rate, and ovarian hyperstimulation syndrome rate were the secondary outcomes. Of the 69 patients, 48 ovulated after the 7-day and 16 after the 10-day regimen. Overall, the cumulative ovulation rate reached 92.75% (64/69) after the 2-step extended LE regimen, with a cumulative clinical pregnancy rate of 31.88% (22/69) and a cumulative live birth rate of 24.63% (17/69). All patients ovulated spontaneously without exogenous trigger agents and none experienced ovarian hyperstimulation syndrome. Extending LE treatment duration is a feasible method for inducing ovulation in women with PCOS and LE resistance.