Ovarian Stimulation Protocols Research Articles

Efficacy of progestin-primed ovarian stimulation in women with polycystic ovary syndrome undergoing in vitro fertilization: a systematic review and meta-analysis.

NPLASY (202340059). https://inplasy.com/inplasy-2023-4-0059/.

From oocytes to a live birth: Are we improving the biological efficiency?

The objectives of our study were to investigate the live birth rate (LBR) per oocyte retrieved during invitro fertilization, in patients who had used all their embryos and to extrapolate the LBR in patients with remaining frozen embryos by calculating the expected LBR from these embryos. A retrospective cohort study. A single academically affiliated fertility clinic. Autologous invitro fertilization cycles from January 2014 to December 2020. Data on the number of oocytes retrieved, number of embryos obtained and transferred (at cleavage or blastocyst-stage), use of preimplantation genetic testing for aneuploidy (PGT-A), and number of live births were obtained. The expected LBR was estimated in patients with remaining frozen embryos according to nationally reported Society for Assisted Reproductive Technology LBR data. None. Live birth rate per oocyte retrieved. A total of 12,717 patients met the inclusion criteria and underwent a total of 20,677 oocyte retrievals which yielded a total of 248,004 oocytes and 57,268 embryos (fresh and frozen). In patients who had fully utilized all their embryos the LBR per oocyte was 2.82% (ranging from 11.3% aged <35 years to 1.2% aged >42 years). Stratification of the population based on PGT-A utilization yielded similar results (with PGT-A: 2.88% and without PGT-A: 2.79%). When stratified by the Society for Assisted Reproductive Technology age groups, the addition of PGT-A in patients aged 35-37 and 38-40 years yielded higher LBR per oocyte compared with patients who did not add PGT-A (P<.05). In patients with remaining frozen embryos who had added PGT-A, the projected LBR per oocyte was 8.34%. Use of PGT-A in patients aged <35 and 35-37 years decreased LBR per oocyte (P<.001 and P=.03, respectively) but improved LBR per oocyte in patients aged 38-40 and 41-42 years (P=.006 and P=.005, respectively). Poisson regression analysis demonstrated an age threshold of 38.5, below which PGT-A lowers LBR per oocyte compared with no PGT-A. Despite clinical and scientific advances in Assisted Reproductive Technology, with the current protocols of ovarian stimulation, the LBR per oocyte remains low reflecting a biological barrier that has yet to be overcome. Overall, the addition of PGT-A did not demonstrate improved outcomes.

Comparison of Cumulative Live Birth Rates between Flexible and Conventional Progestin-Primed Ovarian Stimulation Protocol in Poor Ovarian Response Patients According to POSEIDON Criteria: A Cohort Study.

To compare the cumulative live birth rate (CLBR) per oocyte retrieval cycle of a conventional progestin-primed ovarian stimulation (cPPOS) regimen with a flexible progestin-primed ovarian stimulation (fPPOS) regimen in poor ovarian response patients, according to POSEIDON criteria. Poor ovarian response women, according to POSEIDON criteria, who underwent the first PPOS protocol for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) between January 2018 and December 2020 were included. The fPPOS group involved 113 participants, and the cPPOS group included 1119 participants. In the cPPOS group, medroxyprogesterone acetate (MPA) (10 mg/d) was administrated on the gonadotropin injection the same day as gonadotropin injections in the cPPOS group, while MPA was started either on the day when the leading follicle with mean diameter > 12mm was present and/or serum E2 was >300 pg/mL in the fPPOS protocol group. The primary outcome was CLBR. The fPPOS protocol had higher CLBR per oocyte retrieval cycle compared to the cPPOS group, even without a statistically significant difference (29.6% vs. 24.9%, p = 0.365). The fPPOS group had fewer numbers of retrieved oocytes (2.87 ± 2.03 vs. 3.76 ± 2.32, p < 0.001) but a higher MII oocyte rate (89.8% vs. 84.7%, p = 0.016). In addition, the number of available embryos in the two groups was comparable (1.37 ± 1.24 vs. 1.63 ± 1.38, p = 0.095). There were five women in the fPPOS group, and 86 women in the cPPOS group had a premature LH surge (4.2% vs. 6.8%, p = 0.261). In the fPPOS group, there was one instance of premature ovulation, while in the cPPOS group, there were six occurrences of premature ovulation (0.8 vs. 0.5%, p = 1.000). The novel fPPOS protocol appears to achieve higher CLBR even without significant differences and with MPA consumption compared with cPPOS protocol in low-prognosis patients.

Progestin-primed ovarian stimulation versus GnRH antagonist protocol in ICSI cycles in patients with different ovarian reserve: A retrospective cohort study

Progestin-primed ovarian stimulation versus GnRH antagonist protocol in ICSI cycles in patients with different ovarian reserve: A retrospective cohort study

Hormonal Pretreatment for Ovarian Stimulation: A Narrative Review

Introduction: Assisted reproductive technologies are necessary and important for the management of infertility and can be applied with and without the use of strategies such as hormonal pretreatment. However, there is a discussion in the literature on whether hormonal pretreatment in ovarian stimulation protocols can improve the outcome of oocytes and embryos. This study aimed to conduct an integrative review of hormonal pretreatment and its impact on women undergoing assisted reproduction procedures. Methods: We made searches in the PubMed and the Cochrane Library databases. The inclusion criteria were articles published in peer-reviewed journals in English, Portuguese, or Spanish from January 1, 2010 to December 31, 2021 and available as free full texts. We excluded gray literature works, including term papers, theses, and dissertations. We used a narrative synthesis for data analysis. Results: The 189 articles retrieved from the two databases (2010-2021) were narrowed down to eight articles. In most studies, pretreatment seems to play a role beyond stimulation that includes an early inhibition of the FSH peak, a more homogeneous cohort, and better results. Conclusions: Using a pretreatment with combined oral contraceptives (COC) produces conflicting results in assisted reproduction. The COC improves the quantity and quality of eggs, but it neither benefits nor harms reproductive outcomes. Also, the use of COC has contradictory results regarding clinical pregnancy

Analysis of cumulative live birth rate outcomes of three ovarian stimulation protocols in patients after laparoscopic cystectomy of ovarial endometrioma: a retrospective cohort study

BackgroundPrevious studies have reported that after laparoscopic cystectomy of ovarial endometrioma, the ovarian response to gonadotropin (Gn) significantly decreased. However, for patients with diminished ovarian reserve (DOR) after ovarian surgery, how to choose the most appropriate controlled ovarian hyperstimulation protocol has not been concluded. Compared with the traditional agonist regimen, the gonadotropin (Gn)-releasing hormone (GnRH) antagonist, microstimulation, and progestin-primed ovarian stimulation (PPOS) protocols are simple to operate and have a shorter cycle, which are often used in patients with DOR. So the purpose of our study is to compare the assisted reproductive outcomes of these three controlled ovarian hyperstimulation protocols in patients with DOR following laparoscopic cystectomy of ovarial endometrioma.MethodsIn this retrospective cohort study, 89 patients with DOR who had undergone in vitro fertilisation/intracytoplasmic sperm injection at the Department of Reproductive Medicine at the Third Affiliated Hospital of Zhengzhou University from 1 to 2018 to 31 December 2020 were included. According to the controlled ovarian hyperstimulation protocols employed, the patients were divided into GnRH antagonist (38 patients), PPOS (27 patients), and microstimulation (24 patients) groups. The basic data and clinical outcomes of the three groups were compared. The main outcome measure was the cumulative live birth rate.ResultsNo significant differences in the age of the female patients and their spouses and female patients’ body mass index and basal endocrine levels (follicle-stimulating hormone and oestradiol) were noted among the three groups (P > 0.05). The GnRH antagonist group had higher antral follicle counts, greater endometrial thickness on the human chorionic Gn injection day, greater number of oocytes retrieved, and higher two pronuclear embryo counts than did the other two groups. However, the starting dosage of Gn was lower in the GnRH antagonist group than in the other two groups. The microstimulation group had a significantly higher oocyte output rate and high-quality embryo rate than did the other two groups (P < 0.05). No significant differences in the total dosage of Gn, cumulative pregnancy rate, cumulative live birth rate, viable embryo rate, and blastocyst formation rate were observed among the three groups (P > 0.05).ConclusionIn conclusion, for patients aged under 40 years who experienced DOR after laparoscopic cystectomy of ovarial endometrioma, GnRH antagonist protocol and PPOS protocol can obtain better ovulation induction outcomes and cumulative live birth rate than microstimulation protocol, and are more suitable ovulation induction protocols.

The role of serum vitamin D in patients with normal ovarian reserve undergoing the first IVF/ICSI cycle.

The debate over the impact of vitamin D in assisted reproduction continues. The purpose of our study was to assess embryo quality and pregnancy outcomes among groups with different levels of vitamin D after the first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycle in patients with normal ovarian reserve (NOR). Patients in this retrospective cohort study were divided into three groups: severe vitamin D deficiency group (25OH-D < 10 ng/ml), vitamin D deficiency group (10 ng/ml ≤ 25OH-D < 20 ng/ml), and non-vitamin D deficiency group (25OH-D ≥ 20 ng/ml). The primary outcome was clinical pregnancy, while the secondary outcomes were mature oocytes, oocyte fertilization, available cleavage embryos, available blastocysts, biochemical pregnancy, early abortion, and embryo implantation. A modified Poisson regression model and multiple linear regression analysis were conducted for the multivariate analysis. 264 NOR patients undergoing the first IVF/ICSI cycles were included. For the primary outcome, there was no significant difference in clinical pregnancy between the severe vitamin D deficiency group and the other two groups (vitamin D deficiency group: adjusted RR = 1.026; 0.780 - 1.350; P = 0.854; non-vitamin D deficiency group: adjusted RR = 1.092; 0.743 - 1.605; P = 0.652). For all secondary outcomes, no significant differences were observed among the severe vitamin D deficiency, vitamin D deficiency, and non-vitamin D deficiency groups (P > 0.05). Exploratory subgroup analyses concerning the season of embryo transfer, phase of embryo transferred, and endometrial thickness, as well as the sensitivity analysis using logistic regression models for the primary outcome, revealed comparable clinical pregnancy rates among the groups (P > 0.05). Subgroup analysis concerning ovarian stimulation protocol indicated that in the subgroup of gonadotrophin-releasing hormone (GnRH) antagonist protocol, the clinical pregnancy rate of the non-vitamin D deficiency group was significantly higher than that of the other two groups (P < 0.05). Serum vitamin D level was not associated with embryo quality and pregnancy outcomes for patients with NOR. Further studies with greater sample sizes and a longer follow-up period are needed to elucidate the relationships between vitamin D levels and IVF outcomes.

The clinical value of progestin-primed ovarian stimulation protocol for women with diminished ovarian reserve undergoing IVF/ICSI: a systematic review and meta-analysis.

To determine whether progestin-primed ovarian stimulation (PPOS) is more effective for women with diminished ovarian reserve (DOR) than clomiphene citrate (CC)/letrozole (LE) plus gonadotropin in IVF or ICSI treatment. Nine databases were searched until May 24, 2023, to identify relevant studies. Forest plots were used to present the results of this meta-analysis. Begg's and Egger's tests were applied to estimate publication bias. Subgroup and sensitivity analysis were performed to check the potential sources of heterogeneity and verify the robustness of the pooled results, respectively. A total of 14 studies with 4182 participants were included for meta-analysis. There was evidence of a statistically notable increase in clinical pregnancy rate (OR = 1.39, 95%CI [1.01, 1.91], p = 0.05), optimal embryos rate (OR = 1.50, 95%CI [1.20, 1.88], p = 0.0004), and cumulative pregnancy rate (OR = 1.73, 95%CI [1.14, 2.60], p = 0.009), the duration and the amount of gonadotropin required (MD = 1.56, 95%CI [0.47, 2.66], p = 0.005; SMD = 1.51, 95%CI [0.90, 2.12], p < 0.00001), along with decrease cycle cancellation rate (OR = 0.78, 95%CI [0.64, 0.95], p = 0.02), luteinizing hormone (LH) level on the day of hCG (SMD = -0.81, 95%CI [-1.10, -0.53], p < 0.00001), and premature LH surge rate (OR = 0.10, 95%CI [0.07, 0.15], p < 0.00001) when PPOS was used. No evidence for publication bias within results was revealed. Based on evidence-based results, PPOS protocol seems to improve IVF/ICSI outcomes for women with DOR. More research with larger sample sizes and rigorous designs are required to further explore the value of PPOS among women diagnosed with DOR. www.crd.york.ac.uk, identifier CRD42023430202.

Effects of ovarian stimulation protocols on outcomes of assisted reproductive technology in adenomyosis women: a retrospective cohort study.

To evaluate the effects of different ovarian stimulation protocols on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes in infertile women with adenomyosis. We carried out a retrospective cohort study among infertile women with adenomyosis receiving IVF/ICSI treatment, including 257 fresh embryo transfer (ET) cycles and 305 frozen embryo transfer (FET) cycles. In fresh ET cycles, ultra-long, long, short, and antagonist protocols were adopted. In FET cycles, patients received long-acting GnRH agonist (GnRHa) pretreatment or not. The primary outcome was clinical pregnancy rate (CPR), and the secondary outcomes included implantation rate (IR), miscarriage rate (MR), and live birth rate (LBR). In fresh ET cycles, compared with ultra-long and long protocols, IR (49.7%, 52.1% versus 28.2%, P=0.001) and CPR (64.3%, 57.4% versus 35.6%, P=0.004) significantly decreased in the short protocol. Similarly, compared with ultra-long and long protocols, a decreased inclination of IR (49.7%, 52.1% versus 33.3%) and CPR (57.4%, 64.3% versus 38.2%) existed in the antagonist protocol, although no statistical significance was detected because of strict P adjustment of Bonferroni method (Padj=0.008). Compared with long protocol, LBR in short protocol decreased obviously (48.2% versus 20.3%, P<0.001). In FET cycles, no matter which origin of embryos, there were no statistical differences in IR, CPR, and LBR. For women ≥35 years receiving fresh ET, CPR was higher in ultra-long and long protocols (52.1%, 50.0% versus 20.0%, 27.5%, P=0.031) compared to antagonist and short protocols. For women ≥35 years receiving FET, compared with ultra-long and antagonist protocols, cycles with embryos originating from long and short protocols had higher proportions of long-acting GnRHa pretreatment (30.4%,30.00 versus 63.9%, 51.4%, P=0.009). IR (61.1%, 48.6% versus 32.6%, 25.0%, P=0.020) and CPR (58.3%, 48.6% versus 30.4%, 25.0%, P=0.024) in long and short protocols were higher than rates of ultra-long and antagonist protocols, but no statistical differences were supported because of strict Bonferroni method (Padj=0.008). In infertile women with adenomyosis, if a fresh embryo was planned for transfer, an ultra-long or long protocol might be beneficial. If antagonist and short protocols were used, whole embryos frozen followed by FET was recommended. In FET cycles, embryos derived from different protocols had no impact on pregnancy outcomes.

Fertility preservation after gonadotoxic treatments for cancer and autoimmune diseases

BackgroundThe indications for fertility preservation (FP) have expanded. A few patients who underwent gonadotoxic treatment did not have the opportunity to receive FP, leading to concerns that these patients may develop premature ovarian insufficiency. However, the usefulness of FP in women with reduced ovarian reserve has also been questioned. Progestin-primed ovarian stimulation can improve the controlled ovarian stimulation (COS) protocol, but there is limited data on the efficacy of FP with progestin-primed ovarian stimulation.MethodsWe conducted a prospective study of 43 women with cancer or autoimmune diseases before and after gonadotoxic treatment at the reproductive unit of Keio University Hospital, counselled between 1 January 2018 and 31 December 2021. After counselling, informed consent was obtained for FP from 43 patients, with those who underwent gonadotoxic treatment of the primary disease being prioritised. Gonadotropin-releasing hormone analogue or progestin was used to suppress luteinising hormone in COS before or after gonadotoxic treatment. The number of cryopreserved mature oocytes was the primary outcome.ResultsForty-three patients and 67 assisted reproductive technology cycles were included in the analysis. The median age at entry was 32 [inter quartile range (IQR), 29–37] years. All patients in the post-gonadotoxic treatment group had their oocytes frozen. Gonadotoxic treatment resulted in fewer oocytes [median 3 (IQR 1–4); pre-gonadotoxic treatment group: five patients, 13 cycles] vs. median 9 (IQR 5–14; pre-gonadotoxic treatment group: 38 patients, 54 cycles; P < 0.001). Although anti-Müllerian hormone levels were lower in the post-gonadotoxic treatment group (n = 5, 13 cycles, median 0.29 (IQR 0.15–1.04) pg/mL) than in the pre-gonadotoxic treatment group (n = 38, 54 cycles, median 1.89 (IQR 1.15–4.08) pg/mL) (P = 0.004), oocyte maturation rates were higher in the post-gonadotoxic treatment group [median 100 (IQR 77.5–100) %] than in the pre-gonadotoxic group [median 90.3 (IQR 75.0–100) %; P = 0.039]. Five patients in the pre-gonadotoxic treatment group had their cryopreserved embryos thawed, of which three had live births.ConclusionsOocytes obtained for FP from women with cancer or autoimmune disease for FP are of satisfactory quality, regardless of whether they are obtained post-gonadotoxic treatment or COS protocols.

Progestin Primed Ovarian Stimulation (PPOS) protocol yields lower euploidy rate in older patients undergoing IVF

BackgroundTo explore if exogenous progestin required for progestin primed ovarian stimulation (PPOS) protocol compromises the euploidy rate of patients who underwent preimplantation genetic testing cycles when compared to those who received the conventional gonadotropin-releasing hormone (GnRH) antagonist protocol.MethodsThis retrospective cohort study analyzed 128 preimplantation genetic testing for aneuploidy (PGT-A) cycles performed from January 2018 to December 2021 in a single university hospital-affiliated fertility center. Infertile women aged 27 to 45 years old requiring PGT-A underwent either PPOS protocol or GnRH-antagonist protocol with in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization. Frozen embryo transfers were performed following each PGT-A cycle. Data regarding the two groups were analyzed using the Statistical Package for Social Sciences (SPSS) version 22.0 (SPSS Inc., Chicago, IL).ResultsPatients who underwent PPOS treatment had significantly reduced blastocyst formation rate and euploidy rate compared to those who received the GnRH antagonist protocol. Subgroup-analysis was performed by stratifying patients’ age into elder and young subgroups (elder: ≥ 38-year-old, young: < 38-year-old). In the elder sub-population, the blastocyst formation rate of the PPOS group was significantly lower than that of the GnRH-antagonist group (45.8 ± 6.1% vs. 59.9 ± 3.8%, p = 0.036). Moreover, the euploidy rate of the PPOS group was only about 20% of that of the GnRH-antagonist group (5.4% and 26.7%, p = 0.006). In contrast, no significant differences in blastocyst formation rate (63.5 ± 5.7% vs. 67.1 ± 3.2%, p = 0.45) or euploidy rate (30.1% vs. 38.5%, p = 0.221) were observed in the young sub-population. Secondary outcomes, which included implantation rate, biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and miscarriage rate, were comparable between the two treatment groups, regardless of age.ConclusionWhen compared to the conventional GnRH-antagonist approach, PPOS protocol could potentially reduce the euploidy rate in aging IVF patients. However, due to the retrospective nature of this study, the results are to be interpreted with caution. Before the PPOS protocol is widely implemented, further studies exploring its efficacy in larger populations are needed to define the optimal patient selection suitable for this method.Trial registrationHuman Investigation and Ethical Committee of Chang Gung Medical Foundation (202200194B0).

The value of LH maximum level in predicting optimal oocyte yield following GnRH agonist trigger.

Risk factors associated with a suboptimal response to Gonadotropin-releasing hormone (GnRH) agonists include a high or low body mass index (BMI), prolonged use of oral contraceptive pills, and low luteinizing hormone (LH) levels on either the start or trigger days of controlled ovarian stimulation (COS). However, this approach may increase the need for a dual trigger and may also result in a higher incidence of ovarian hyperstimulation syndrome (OHSS) in hyper-responders. We aimed to investigate whether the maximum LH level during stimulation can serve as a predictive factor for achieving an optimal oocyte yield using the GnRH agonist trigger alone. We retrospectively reviewed all antagonist protocols or progestin-primed ovarian stimulation (PPOS) protocols triggered with GnRH agonist only between May 2012 and December 2022. Subjects were divided into three groups, depending on basal LH level and LH maximum level. The freeze-all strategy was implemented in all cycles: Group 1, consistently low LH levels throughout COS; Group 2, low basal LH level with high LH max level during COS; Group 3, consistently high LH levels throughout COS. The primary outcome was the oocyte yield rate. The secondary outcome includes the number of collected oocytes, suboptimal response to GnRH agonist trigger, oocyte maturity rate, fertilized rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate. The pregnancy outcomes were calculated for the first FET cycle. Following confounder adjustment, multivariable regression analysis showed that Group 1 (cycles with consistently low LH levels throughout COS) remains an independent predictor of suboptimal response (OR: 6.99; 95% CI 1.035-47.274). Group 1 (b = -12.72; 95% CI -20.9 to -4.55) and BMI (b = -0.25; 95% CI -0.5 to -0.004) were negatively associated with oocyte yield rate. Patients with low basal LH but high LH max levels had similar clinical outcomes compared to those with high LH max levels through COS. The maximum LH level during COS may serve as an indicator of LH reserve and could be a more reliable predictor of achieving an optimal oocyte yield when compared to relying solely on the basal LH level. In the case of hyper-responders where trigger agents (agonist-only or dual trigger) are being considered, we propose a novel strategy that incorporates the maximum LH level, rather than just the basal or trigger-day LH level, as a reference for assessing LH reserve. This approach aims to minimize the risk of obtaining suboptimal oocyte yield and improve overall treatment outcomes.

Artificial Insemination Pregnancy Program as a Type of Service and Level of Efficiency of Health Services

The purpose of this study is to look at the artificial insemination pregnancy program service as one of the services at Mutiara Bunda Mother and Child Hospital. In this context, it will also look at the perspective of its management efficiency. The pregnancy program with this method involves the age of female and male patients, endometrial thickness (EMT), post-washing total motile sperm count (PTMC), artificial insemination time, insemination frequency, and ovarian stimulation protocol which are compared between the pregnant group and the non-pregnant group to see any correlation. Then, hospital efficiency reflects the ratio of the value of health services provided, both quantity and quality of care to the resources used in health services. This study was conducted at Mutiara Bunda Mother and Child Hospital Padang. The results of the study state that procedurally and institutionally, the pregnancy program service with artificial insemination at RSIA Mutiara Bunda Padang is very good. Specialist doctors and other paramedics are well qualified to implement this service program. The Director of the Mother and Child Hospital includes effective leadership because the performance of staff or officers at the Mother and Child Hospital has worked well, with the motivation provided by the leadership. The hospital has adequate specialist doctors, both in terms of number and type of specialization in accordance with hospital specifications, namely Obgyn and Pediatric specialists. The artificial Insemination Pregnancy Program as a type of service is the first in Padang

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.

Predicting the total number of retrieved oocytes following double ovarian stimulation (DuoStim).

Can anti-Müllerian hormone (AMH) help predict how many oocytes will be retrieved following double stimulation (DuoStim)? A simple clinical tool can use serum AMH values to predict ovarian response following DuoStim in IVF cycles. The knowledge that multiple follicular waves arise during a single ovarian cycle has led to the introduction of unconventional ovarian stimulation protocols. The DuoStim protocol involves two successive ovarian stimulations performed during a single ovarian cycle and has been proposed as an approach for patients with poor ovarian response and for medical fertility preservation. As AMH has been used as a marker of ovarian reserve and stimulation response, the current study aimed to investigate the diagnostic performance of AMH in predicting the number of retrieved oocytes following DuoStim. This is a retrospective observational study involving 116 patients who received IVF treatment from January 2021 to September 2022. The study was conducted at a private IVF centre. Only patients who had their AMH measured prior to treatment and had complete patient records regarding their clinical and IVF/ICSI cycle characteristics were included. The primary outcome was the correlation between AMH values and the number of oocytes retrieved following DuoStim. Parametric and non-parametric tests were used to compare baseline characteristics and outcomes. Spearman's R was used to analyse correlations between variables, while the C statistic was used to calculate the diagnostic performance of AMH. AMH levels were significantly correlated with the total number of oocytes retrieved after the DuoStim (R 0.61; CI 0.44-0.70; P < 0.0001). The difference in the total number of oocytes retrieved between the first (median 4 oocytes, interquartile range (IQR) 2-6) and second (median 6 oocytes, IQR 3.2-8) stimulation was statistically significant (P < 0.0001). However, there was no significant difference in the number of mature oocytes that were retrieved (median of 3 and 4 in the first and second stimulations, respectively). After the first stimulation, 68% of patients had at least one blastocyst available, while after the second stimulation, 74% did (NS). Based on linear regression, each 0.25 ng/ml increase in basal AMH corresponds to one additional oocyte recovered at the end of both stimulations (R2: 0.32, P < 0.0001). The results are limited owing to the observational nature of the study and the number of participants. Counselling infertile couples regarding the intermediate outcome of IVF (i.e. number of retrieved oocytes) is one of the most demanding tasks that clinicians face. To our knowledge, this is the first study that provides an easy-to-use clinical tool that enables the quantitative prediction of ovarian response following DuoStim, based on serum AMH values. No external funding was obtained for this study. The authors declare no conflicts of interest. N/A.

P-728 Impact of calling mosaicism for a less stringent threshold on clinical pregnancies in more than 6000 PGT-A cycles

Abstract Study question How does calling mosaicism for a higher threshold affect euploidy, the chance of finding at least one euploid embryo and clinical pregnancy? Summary answer Increasing the threshold significantly increased euploidy percentage and the probability of finding at least one euploid embryo, as expected, but also the pregnancy outcomes. What is known already NGS technology has shed light on the occurrence of chromosomal mosaicism at the preimplantation stage of development. Evidence regarding clinical outcomes after transfer of embryos with putative mosaic results are accumulating (ESHRE Working Group on Chromosomal Mosaicism, 2022). A series of studies reporting the birth of healthy babies after the transfer of embryos with a chromosomal mosaic result on PGT-A (Greco et al., 2015; Kahraman et al., 2020; Viotti et al., 2019 and 2021), have been published. Data suggested lower implantation rates and higher miscarriage rates when mosaics were compared with euploid embryo transfers. Study design, size, duration This retrospective study covers a period from January 2017 to October 2022 and includes 6063 PGT-A cycles. A total of 18425 blastocysts were biopsied and analyzed with NGS. From January 2017 to December 2020, the cut-off value for reporting mosaicism and euploidy was %20; the rate of which was increased to 30% after January 2021. Chromosomes with PGT-A profiles that deviate from 2 copies by less than 30% were reported as normal. Participants/materials, setting, methods A total number of 12751 and 5674 blastocysts were biopsied between January 2017-December 2020 and January 2021-October 2022, respectively. PGT-A was performed on Ion Torrent S5 (Thermo Fisher Scientific). The mean female age for 20% and 30% cut-off groups were 36.7+-5.1, 35.9+-5.2, respectively. As this age difference was statistically significant, further analysis was performed in age subgroups &amp;lt; =38 and &amp;gt;38. Main results and the role of chance For PGT-A cycles with female age &amp;lt; =38, cycles with at least one euploid embryo in the 30% cut-off group increased from 74.0% to 77.5% whereas cycles with at least one mosaic embryo decreased from 40.8% to 37.0% (p = 0.0212; p = 0.0274). Cycles with at least one mosaic embryo without any euploid embryos decreased by 2% (9.2% to 7.2%) (p = 0.0522). The euploidy percentage out of all tested biopsies was significantly increased from 40.4% to 45.8% (p = 0.0001). For cycles with female age &amp;gt;38, ratio of PGT-A cycles with at least one euploid embryo increased from 28.1% to 30.3% in the 30% cut-off group but this was not statistically significant (p = 0.28). Cycles with at least one mosaic embryo were decreased from 15.1% to 10.8% and cycles with at least one mosaic embryo without any euploid embryo decreased from 9.5% to 5.6% in the 30% cut-off group (p = 0.006; p = 0.0018). The euploidy percentage was increased by 2.8% from 15.1% to 18.1% (p = 0.0115). The pregnancy outcomes were significantly higher for euploid embryos with the 30% cut-off compared to 20%, as clinical pregnancy was 64.5% vs. 59.1% and clinical pregnancy loss was 7.9% vs. 12.4% (p = 0.0022; p = 0.0011). Similarly, ongoing pregnancy was 5.2% higher, but non-significant. Limitations, reasons for caution These are the results of a single ART center which is using the same protocols for ovarian stimulation and endometrial preparation in the two periods above mentioned. Although not expected, minor changes may have occurred; similar practices have to be reported. Wider implications of the findings Mosaicism is undeniably a true biological phenomenon. However, trophectoderm biopsy and NGS are prone to create an artefactual false mosaicism. Relaxing the mosaicism calling rate by 10% may have added some better-quality blastocysts to the euploid pool giving the opportunity to embryologists of transferring blastocysts with higher implantation potential. Trial registration number Not applicable

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

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

P-662 Embryo ploidy rates following PPOS or GnRH antagonist protocol. A prospective study with repeated ovarian stimulation

Abstract Study question Is there any difference in embryo ploidy rates following progesterone primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? Summary answer Pituitary downregulation with a PPOS protocol with micronized progesterone results in a comparable number of euploid blastocysts with a GnRH antagonist protocol. What is known already Although the GnRH antagonist is consider by most the gold standard protocol for controlling the LH surge during ovarian stimulation for IVF/ICSI, progesterone-primed ovarian stimulation protocols (PPOS) are being increasing used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in equivalent blastocyst euploidy rates as compared with a GnRH antagonist protocol. Study design, size, duration In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive ovarian stimulation (OS) protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. Participants/materials, setting, methods Overall, 44 women underwent two OS cycles with identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the 1st cycles was performed with the use of a flexible GnRH antagonist protocol and consecutively, after a washout period of one month, control of LH surge was performed with oral micronized progesterone from stimulation day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (PGT-A). Main results and the role of chance Comparisons between cycles did not reveal differences between the duration of OS neither in the gonadotrophins dose. Hormonal profile on the day of trigger revealed statistically significant differences between cycles in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher Progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. PPOS protocol resulted in a significantly higher number of oocytes (10.27± 5.84 versus 12.68± 8.09), (DBM -2.4 [95% CI -4.1; -0.73]), MIIs (7.34±4.15 versus 9.09± 6.12), (DBM -1.8 [95% CI -3.1; -0.43]), and 2PNs (5.66±3.35 versus 7.14± 4.99), (DBM -1.5 [95% CI -2.6.1; -0.32]) as compared with the GnRH antagonist protocol. Nevertheless, no differences were observed regarding the mean number of blastocysts (2.84±2.12 versus 2.91±2.11), (DBM -0.07 [95% CI -0.67; 0.53]) and the mean number of biopsied blastocysts (2.86±2.15 versus 2.93±2.16), (DBM -0.07 [95% CI -0.70; 0.56]). Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 vs. 1.00 ± 1.12 for the comparison of PPOS vs. GnRh antagonist. Limitations, reasons for caution The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol there was no randomisation, the first cycle was always a GnRH antagonist cycle and the 2nd a PPOS with one month of washout period in between. Wider implications of the findings The current study provides evidence that the PPOS may result in equivalent blastocyst euploidy rates compared with antagonist protocol. This may imply that in case of a freeze-all protocol, clinicians may safely consider PPOS to control the LH surge and patients could benefit from the advantages (cost and oral administration). Trial registration number NCT04108039

P-281 Single-cell RNA sequencing analysis of granulosa cells in preovulatory follicles in normal ovarian reserve patients undergoing progestin-primed ovarian stimulation and GnRH-antagonist

Abstract Study question Could the difference in controlled ovarian stimulation protocol between progestin-primed ovarian stimulation and GnRH-antagonist induce change in the expression genes of human granulosa cells? Summary answer The mitochondrial DNA (mtDNA) gene expression of granulosa cells in patients who underwent progestin-primed ovarian stimulation was significantly higher than the GnRH-antagonist. What is known already The progestin-primed ovarian stimulation (PPOS) protocol has attracted attention and many studies have reported similar pregnancy outcomes for both PPOS and the GnRH-antagonist (GnRH-ant). However, our previous study demonstrated that pregnancy rate was significantly lower in PPOS compared to GnRH-ant (38th Hybrid Annual Meeting of the ESHRE, O-130). In this study, we evaluated the gene expression of granulosa cells (GCs) which affects reproductive outcome. Many studies have shown a close association between the mitochondrial status of GCs and embryo’s quality. To date, the change in gene expression of GCs with different controlled ovarian stimulation protocols have not been investigated. Study design, size, duration From November 2021 to January 2022, all samples were obtained from the patients who provided written informed consent before the inclusion and underwent controlled ovarian stimulation cycles at a single-institution. Single cell RNA-seq (scRNA-seq) was performed on 2,224 cells corresponding to GCs of the MII-oocyte follicles from a total of 16 patients with normal ovarian reserve (aged &amp;lt; 40 years, AMH ≧1.1 ng/mL) undergoing PPOS with chlormadinone acetate (n = 8), or GnRH-ant with cetrorelix (n = 8). Participants/materials, setting, methods The GCs were obtained by follicular aspiration from 16 patients undergoing oocyte retrieval. The follicular fluid (FF) from each follicle was collected and all FF were mixed together in MII-oocyte for sequencing. The GCs were isolated from the blood cells and cellular debris using Percoll gradient centrifugation. Samples for sequencing were prepared using Chromium Next GEM Single Cell V(D)J Reagent Kits. Libraries were sequenced in DNBSEQ-G400, and reads processed with CellRanger and visualized with CellxGene. Main results and the role of chance Two population of GCs were used in this investigation: PPOS and GnRH-ant of MII-oocyte. After the quality control, 1,197 cells for PPOS and 1,027 cells for GnRH-ant, respectively, were analyzed. The GCs of MII-oocyte were clustered into 6 groups based on Leiden algorithm and visualized by UMAP analysis. There was no significant difference in the gene expression and cell distribution in each cluster. In the two population of GCs, we identified 12 differentially expressed genes (DEGs). Interestingly, we observed significant increase in expression of mtDNA genes in PPOS of MII-oocyte as compared to GnRH-ant of MII-oocyte. The data were confirmed by qRT-PCR analysis. Limitations, reasons for caution Our conclusions are limited due to the inclusion of Asian patients at a single-institution. The results need to be validated across different centers and other ethnicities. Due to the small sample size, these results should prompt further study to confirm our findings. Wider implications of the findings These findings describe, for the first time, the DEGs of GCs investigated in different COS protocols at single-cell level. This study suggests that progestin for PPOS induce elevation of the mt DNA gene expression of GCs which may be associated with reproductive outcomes. Trial registration number Not applicable

P-635 RELATION BETWEEN THE TIME OF CONTROLLED OVARIAN STIMULATION IN PROGESTIN AND GnRH ANTAGONIST PROTOCOLS AND THE OUTCOMES OF IVF – A RETROSPECTIVE OBSERVATIONAL STUDY

Abstract Study question Comparison between IVF outcomes of two controlled ovarian stimulation (COS) protocols (the antagonist protocol and the progestin protocol) and their duration. Summary answer This data suggests that the protocols have comparable efficiency on the ovarian stimulation, leading to similar outcomes on IVF treatments. What is known already Both protocols aim to prevent early ovulation by blocking the LH surge but have slightly different mechanisms: the antagonist protocol uses a GnRH antagonist to block LH whereas in the progestin protocol a progestogen is administered. The aim of COS is to stimulate follicular growth for oocyte punction, avoiding an early ovulation. In this sense, some studies have shown that the use of oral dydrogesterone can offer a more stable maintenance of LH levels, with less occurrence of an early peak of this hormone, leading to fewer cases of premature ovulation and cycle cancellation. Study design, size, duration In this retrospective observational study data were collected from patients undergoing in vitro fertilization (IVF) treatment at Instituto Ideia Fértil between September 2019 and September 2020. The study was submitted to the evaluation of the Ethics and Research Committee (CEP) of the Faculdade de Medicina do ABC (CAAE: 54150621.8.0000.002) and approved. A total of 447 patients were included in the study, with 205 undergoing the antagonist protocol and 242 the progestin protocol. Participants/materials, setting, methods The participants were women of reproductive age that have undergone IVF at Instituto Ideia Fértil between September 2019 and 2020. They were divided between two groups: L-COS, which refers to cycles lasting ≥ 9 days, and S-COS, with cycles lasting ≤ 8 days. The variables included in the statistical analysis were: age, basal antral follicle count, and numbers of days of COS, collected and MII oocytes, zygotes, cleaved embryos and blastocysts. Main results and the role of chance Of the 447 patients, 392 underwent L-COS and 55 S-COS. Mean age was 38.5. When comparing groups, there was no statistical difference in the basal AFC (antral follicle count), average of recovered oocytes, mature oocytes, cleaved embryos, and blastocysts. There was a difference in the mean number of zygotes, which was greater in the L-COS group (2.77 ± 2.38 - 2.05 ± 2.16; p &amp;lt; 0.05). However, the final outcome did not show superiority, since the number of cleaved embryos and blastocysts did not show a significant difference. There were no significant differences between the L-COS and S-COS groups of women submitted to the progestin protocol for any outcomes. When comparing the outcomes of the L-COS and S-COS groups of women submitted to the antagonist protocol, a significant difference in the basal AFC was observed, which was higher in the L-COS group (3.87 ± 1.69 - 3.0 ± 1.57; p &amp;lt; 0.05), which may justify the need for more days of ovulation induction for oocyte growth and maturation. No other outcomes showed a significant difference between groups. Therefore, the duration of the COS does not appear to have an impact on outcomes in either the progestin or antagonist protocols. Limitations, reasons for caution The limitations of this study are the lack of data on BMI (body mass index), pregnancy rate and live birth rate, which does not allow us to analyze the future success of each of the ovarian stimulation protocols or trace the relationship between BMI and IVF. Wider implications of the findings This study showed no relevant differences between protocols. As the progestin protocol is cheaper and easier to administer and seems to have the same quality as the antagonist protocol it might be an interesting alternative, despite another step on the treatment, the freeze all. Trial registration number CAAE: 54150621.8.0000.002