In Vitro Fertilization Cycles Research Articles

The utility of all-freeze IVF cycles depends on the composition of study populations

BackgroundBecause often introduced without proper validation studies, so-called “add-ons” to IVF have adversely affected in vitro fertilization (IVF) outcomes worldwide. All-freeze cycles (embryo banking, EB) with subsequently deferred thaw cycles are such an “add-on” and, because of greatly diverging reported outcomes, have become increasingly controversial. Based on “modeling” with selected patient populations, we in this study investigated whether reported outcome discrepancies may be the consequence of biased patient selection.ResultsIn four distinct retrospective case control studies, we modeled in four cohort pairings how cryopreservation with subsequent thaw cycles affects outcomes differently in good-, average- and poor-prognosis patients: (i) 127 fresh vs. 193 frozen donor-recipient cycles to model best-prognosis patients; (ii) 741 autologous fresh non-donor IVF cycles vs. 217 autologous frozen non-donor IVF cycles to model average prognosis patients; (iii) 143 favorably selected autologous non-donor IVF cycles vs. the same 217 frozen autologous cycles non-donor to monitor good- vs. average-prognosis patients; and (iv) 598 average and poor-prognosis autologous non-donor cycles vs. the same 217 frozen autologous non-donor cycles to model poor vs. average prognosis patients. In best-prognosis patients, EB marginally improved IVF outcomes. In unselected patients, EB had no effects. In poor-prognosis patients, EB adversely affected IVF outcomes. Unexpectedly, the study also discovered independent-of-age-associated chromosomal abnormalities, a previously unreported effect of recipient age on miscarriage risk in donor-egg recipients.ConclusionsIn poor-prognosis patients, EB cycles should be considered contraindicated. In intermediate-prognosis patients EB does not appear to change outcomes, not warranting additional cost and time delays. Therefore, only good-prognosis patients are candidates for EB, though they will experience only marginal benefits that may not be cost-effective.

The association between body mass index and live birth and maternal and perinatal outcomes after in-vitro fertilization: a national cohort study.

To investigate the association between female body mass index (BMI) and live birth rates and maternal and perinatal outcomes after in-vitro fertilization (IVF). We performed a national, population-based cohort study including women undergoing IVF between 2002 and 2020. The cohort included 126,620 fresh cycles and subsequent frozen embryo transfers between 2007 and 2019 (subpopulation 1) and 58,187 singleton deliveries between 2002 and 2020 (subpopulation 2). Exposure was female BMI (kg/m2) categorized according to the World Health Organization as underweight (<18.5), normal weight (18.5-24.9, reference), overweight (25.0-29.9), class I obesity (30.0-34.9), class II obesity (35.0-39.9), and class III obesity (≥40.0). The primary outcome in subpopulation 1 was cumulative live birth per started fresh IVF cycle, including fresh and subsequent frozen embryo transfers. Primary outcomes in subpopulation 2 were hypertensive disorders of pregnancy and preterm birth at less than 37 weeks. Risk ratios (RRs) with 95% confidence intervals (CIs) for the association between BMI class and outcomes were calculated using generalized linear models after adjustment for relevant confounders. The cumulative live birth rate decreased significantly with increasing BMI from 32.6% in normal-weight women to 29.4% in overweight women, 27.0% in women in obesity class I, 21.8% in women in obesity class II, and 7.6% in women in obesity class III. The risk of hypertensive disorders of pregnancy increased significantly and progressively with increasing BMI, from 4.6% in normal-weight women to 7.8% in overweight women and 12.5%, 17.9%, and 20.3% in women in obesity classes I, II, and III. The risk of preterm birth followed a similar pattern, from 6.3% in normal-weight women to 7.5% in overweight women and 8.9%, 9.9%, and 15.3% in women in obesity classes I, II, and III. The risks of other perinatal complications, such as perinatal death, showed an even more pronounced increase. Using a large and complete national cohort of women undergoing IVF, we demonstrate a dose-dependent decrease in live birth rate and a substantial increase in maternal and perinatal complications with increasing BMI. Strategies to improve this situation are warranted.

Outcomes of the Next In Vitro Fertilization Cycle in Women with Polycystic Ovary Syndrome after a Failed In Vitro Maturation Attempt.

In vitro maturation (IVM) is indicated in women with polycystic ovary syndrome (PCOS) who have a very good ovarian response during in vitro fertilization (IVF) and are therefore at high risk of ovarian hyperstimulation syndrome (OHSS). According to the latest practice committee document, IVM could be a major advance in assisted reproductive technology (ART) procedures (reduced cost and simplified treatment); nevertheless, retrospective studies of IVM versus IVF still demonstrate lower chances of a live birth with IVM. Could IVM prove to be an optimal first-line treatment approach? And limited information is available concerning the success of the subsequent IVF cycle after the failure of an IVM cycle. Does IVM treatment adversely affect the subsequent IVF cycle, and is this worth considering before performing the IVF cycle for women with PCOS? This prospective nested case-control study at the Peking University Reproductive Medicine center in China was performed between March 2018 and September 2020. Women aged 20-38 years with PCOS and infertility and who were scheduled for their first IVF attempt were eligible. A total of 351 women were randomly allocated to receive one cycle of unstimulated natural IVM (n = 175) or one cycle of standard IVF with a flexible GnRH antagonist protocol followed by hCG as an ovulation trigger (n = 176). This study involved 234 women (58 women with no blastocysts in the first IVM cycle and 158 women who underwent the first IVF cycle). Cumulative live birth rate at 12 months after oocyte retrieval and OHSS of a standard controlled ovarian stimulation (COS) IVF cycle were compared between 58 women in an IVF cycle following a failed IVM cycle and 158 women who underwent the first IVF cycle. No significant differences were found in the cumulative live birth rate (CLBR), ongoing pregnancy rate, or clinical pregnancy rate at 12 months after oocyte retrieval between the two groups (56.9% vs. 58.9%, p = 0.795; 58.6% vs. 60.8%, p = 0.776; and 84.5% vs. 76.0%, p = 0.178). The incidence of moderate-to-severe OHSS was not significantly different between the groups (6.9% vs. 5.7%, p = 0.742). Additionally, there were no significant differences in the total gonadotropin dose, stimulation duration, number of retrieved oocytes, number of retrieved mature oocytes, or fertilization rates. Even if the first IVM attempt failed in subfertile women with PCOS, comparable cumulative live birth rates were observed in the subsequent IVF cycle. IVM treatment does not adversely affect the subsequent IVF cycle.

Pre-pregnancy obesity is not associated with poor outcomes in fresh transfer in vitro fertilization cycles: a retrospective study

PurposeThe impact of body mass index (BMI) on in vitro fertilization (IVF) has been well acknowledged; however, the reported conclusions are still incongruent. This study aimed to investigate the effect of BMI on IVF embryos and fresh transfer clinical outcomes.MethodsThis retrospective cohort analysis included patients who underwent IVF/ICSI treatment and fresh embryo transfer from 2014 to March 2022. Patients were divided into the underweight group: BMI < 18.5 kg/m2; normal group: 18.5 ≤ BMI < 24 kg/m2; overweight group: 24 ≤ BMI < 28 kg/m2; and obesity group: BMI ≥ 28 kg/m2. A generalized linear model was used to analyze the impact of BMI on each IVF outcome used as a continuous variable.ResultsA total of 3465 IVF/ICSI cycles in the embryo part; and 1698 fresh embryo transplanted cycles from the clinical part were included. Available embryos rate (61.59% vs. 57.32%, p = 0.007) and blastocyst development rates (77.98% vs. 66.27%, p < 0.001) were higher in the obesity group compared to the normal BMI group. Also, the fertilization rate of IVF cycles in the obesity group was significantly decreased vs. normal BMI group (normal: 62.95% vs. 66.63% p = 0.006; abnormal: 5.43% vs. 7.04%, p = 0.037), while there was no difference in ICSI cycles. The clinical outcomes of overweight and obesity groups were comparable to the normal group. The gestational age of the obesity group was lower compared to the normal group (38.08 ± 1.95 vs. 38.95 ± 1.55, p = 0.011). The adjusted OR (AOR) of BMI for the preterm birth rate of singletons was 1.134 [(95% CI 1.037–1.240), p = 0.006]. BMI was significantly associated with live birth rate after excluded the PCOS patients [AOR: 1.042 (95% CI 1.007–1.078), p = 0.018]. In young age (≤ 35 years), clinical pregnancy rate and live birth rate were positively correlated with BMI, AOR was 1.038 [95% CI (1.001–1.076), p = 0.045] and 1.037 [95% CI (1.002–1.074) p = 0.038] respectively.ConclusionBeing overweight and obese was not associated with poor IVF outcomes but could affect blastocyst formation. ICSI could help to avoid low fertilization in obese patients. Also, obesity was associated with increased rates of premature singleton births.

Associations between Urinary Concentrations of Disinfection Byproducts and in Vitro Fertilization Outcomes: A Prospective Cohort Study in China.

Experimental studies show that disinfection byproducts (DBPs) can inhibit oocyte maturation, decrease fertilization capacity, and impair embryo development, but human evidence is lacking. We aimed to evaluate the associations between exposure to drinking water DBPs and in vitro fertilization (IVF) outcomes. The study included 1,048 women undergoing assisted reproductive technology (ART) treatment between December 2018 and January 2020 from a prospective cohort study, the Tongji Reproductive and Environmental study in Wuhan, China. Exposure to DBPs was assessed by dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) in up to four urine samples, which were collected on the day of both enrollment and oocyte retrieval. Multivariable generalized linear mixed models, accounting for multiple IVF cycles per woman, were applied to evaluate the associations between urinary biomarkers of DBP exposures and IVF outcomes. Stratified analyses were used to explore the potential effect modifiers. The included 1,048 women underwent 1,136 IVF cycles, with 960 (91.6%), 84 (8.0%), and 4 (0.4%) women contributing one cycle, two cycles, and three cycles, respectively. We found that elevated quartiles of urinary DCAA and TCAA concentrations were associated with reduced numbers of total oocytes and metaphase II oocytes and that urinary DCAA concentrations with a lower proportion of best-quality embryos (all p for ). Moreover, elevated quartiles of urinary DCAA concentrations were associated with decreased proportions of successful implantation, clinical pregnancy, and live birth (14%, 15%, and 15% decreases in adjusted means comparing the extreme quartiles, respectively; all p for ). Stratification analyses showed that the inverse associations of urinary TCAA concentrations with multiple IVF outcomes were stronger among women y of age (p for ). Exposure to drinking water DBPs was inversely associated with some IVF outcomes among women undergoing ART treatment. Further study is necessary to confirm our findings. https://doi.org/10.1289/EHP12447.

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.

Estradiol serum level on progesterone support day among frozen embryo transfer IVF patients and pregnancy outcomes a systematic review and meta-analysis

Introduction: The relationship between estradiol serum levels on the day of progesterone injection and the outcomes of in vitro fertilization (IVF) pregnancies has been extensively explored in various studies and clinical inquiries. This study aims to conduct a systematic review and meta-analysis to investigate the influence of estradiol serum levels on the day of progesterone injection on pregnancy outcomes in IVF cycles. Method: By conducting a thorough search of the PubMed and Embase databases, a total of eight studies were selected for inclusion in the analysis. The results indicated a risk ratio of 1.34 (95% CI 0.85-2.11) for live birth rate, 0.94 (95% CI 0.90-0.99) for biochemical pregnancy rate, 1.02 (95% CI 0.79-1.31) for clinical pregnancy rate, 0.84 (95% CI 0.51-1.41) for miscarriage rate, 0.81 (95% CI 0.49-1.35) for implantation rate, and a mean difference of -0.01 (95% CI -0.35 to 0.33) for endometrial thickness. Results: The study indicates that there is no significant association between progesterone serum levels on the day of hCG administration and IVF pregnancy outcomes. However, the substantial heterogeneity observed across the included studies underscores the necessity for more comprehensive and standardized investigations to uncover the intricate associations between estradiol levels and IVF success. Conclusion: This research enhances our comprehension of the role of estradiol serum levels in IVF outcomes and lays the groundwork for future studies aimed at refining fertility treatment protocols.

Effect of obstructive sleep apnea on invitro fertilization outcomes in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) confers a high risk of obstructive sleep apnea (OSA). Here we investigated the effect of OSA on first invitro fertilization (IVF) cycle metrics and outcomes in patients with PCOS. This was a prospective cohort study of patients with PCOS undergoing their first IVF at a single tertiary center between October 1, 2021, and September 30, 2022. Patients were screened for OSA before IVF and grouped accordingly. Clinical and IVF cycle data were compared between groups. OSA was found in 37.2% of 156 patients with PCOS, with longer infertility duration (4.3 ± 2.5 vs. 3.4 ± 2.0 years) and lower levels of anti-Müllerian and luteinizing hormones than patients without OSA (6.44 ± 2.96 vs 8.69 ± 4.03 µg/L and 6.30 ± 5.02 vs 8.46 ± 6.09 U/L). Antral follicle count was lower in patients with OSA (28.9 ± 12.4 vs 33.2 ± 12.9). During ovarian stimulation, patients with OSA required significantly higher doses of gonadotropin (2080.8 ± 1008.7 vs 1682.8 ± 619.9 U) and had lower peak estradiol level (4473.5 ± 2693.0 vs 5455.7 ± 2955.1 pmol/L) and fewer retrieved oocytes, high-quality, and available embryos (17.8 ± 7.2 vs 21.9 ± 10.5, 4.5 ± 4.4 vs 6.2 ± 4.6, 5.2 ± 4.3 vs 7.4 ± 5.0). Eleven patients were excluded for having no embryos or missing transfer. Therefore, we analyzed the outcome of the first embryo transfer in 145 patients. The biochemical and clinical pregnancy rates were lower in patients with OSA than patients without OSA (51.9% vs 66.7% and 42.3% vs 60.2%). OSA was independently associated with clinical pregnancy rate after controlling for several confounders (P = .043). OSA impairs female fertility in patients with polycystic ovary syndrome, suggesting an adverse effect on invitro fertilization cycle stimulation characteristics and clinical outcomes. Zhang Q, Wang Z, Ding J, etal. Effect of obstructive sleep apnea on invitro fertilization outcomes in women with polycystic ovary syndrome. J Clin Sleep Med. 2024;20(1):31-38.

Embryo ploidy in vitrified versus fresh oocytes: Is there a difference?

To evaluate embryo ploidy in a cohort of patients who underwent preimplantation genetic testing for aneuploidy (PGT-A) with vitrified oocytes compared to fresh oocytes. Patients who underwent their first autologous oocyte vitrification and warming followed by in vitro fertilization (IVF) and trophectoderm biopsy for PGT-A between 1/1/2017 and 12/31/2021 at a single academic institution were included. Patients were compared 1:3 to age-matched controls who underwent their first IVF cycle with fresh oocytes and subsequent trophectoderm biopsy for PGT-A. The primary outcome was the proportions of euploid, mosaic, and aneuploid embryos between those using vitrified versus fresh oocytes. 117 patients who cryopreserved a total of 1,272 mature oocytes were included in the study and were matched with 351 controls using fresh oocytes. The average age was 36.9 ± 2.6years, and the median interval between oocyte vitrification and warming was 38months. There were similar numbers of mature oocytes (10.9 ± 4.9 vs. 11.1 ± 6.3, P = .67), fertilized oocytes (7.8 ± 4.0 vs. 8.7 ± 5.5, P = .10), and blastocysts per patient (5.1 ± 3.1 vs. 5.8 ± 4.3, P = .10) between those using vitrified versus fresh oocytes. In terms of embryo ploidy results, there were no statistically significant differences in rates of euploidy (40.1% vs. 41.6%), mosaicism (15.7% vs. 12.0%), or aneuploidy (44.3% vs. 46.4%) (P = .06) between the two groups. Oocyte vitrification with subsequent warming, fertilization, and trophectoderm biopsy for PGT-A was not associated with adverse chromosomal competence when compared to age-matched controls utilizing fresh oocytes.

Impacts of COVID-19 Pandemic on Three IVF Clinics of Jakarta, Indonesia: A Retrospective Qualitative and Quantitative Study.

Corona virus disease-19 (COVID-19) pandemic also led to a reduction or even the suspension of elective health services. These decisions affected in vitro fertilization (IVF) programs worldwide. Therefore, it is essential to map the readiness of IVF clinics in providing safety in this situation and in the future. This is a retrospective qualitative and quantitative research done in 2021 that involved three IVF clinics of Jakarta, Indonesia. Those three clinics were government-owned, private-owned, and educational and training center. The qualitative data of each clinic's readiness towards COVID-19 was obtained from interviews with the clinics staff. The quantitative data were collected from the clinics patients' number and demographic data from 2019-2021 as well as from COVID-19 databases. Both data sets were analysed descriptively and only for the quantitative analysis Stata version 16 was used. There were changes in the domiciles and number of patients attending the three clinics. The ratio of patients from Jakarta increased while patients from outside Java Island decreased. There was a drop in annual patient numbers in 2020. However, from June 2020 to December 2021, the number of monthly IVF cycles increased significantly by 3.5 cycles per month (P=0.001). There was no association between IVF patients' attendance numbers and COVID-19 cases (P=0.785). One of the clinics had a negative pressure operating theatre, which made them more confident in treating patients with COVID-19 positive and made them even had higher IVF cycles started than the pre-pandemic period. Those three clinics are prepared in facing COVID-19, as they complied with government regulations. As the COVID-19 pandemic progressed, the number of patients gradually returned to normal.

Endometrial microbiota profile in in-vitro fertilization (IVF) patients by culturomics-based analysis.

It is well recognized that the human uterus and adjoining tissues of the female reproductive tract exist in a non-sterile state where dysbiosis can impact reproductive outcomes. The endometrial microbiota is a part of this greater milieu. To date, it has largely been studied using 16S rRNA or metagenomics-based methodologies. Despite the known advantages of sequencing analysis, several difficulties have been noted including sample contamination and standardization of DNA extraction or sequencing. The aim of this study was to use a culturomics-based method to analyze the endometrial microbiota and correlate the results with ongoing pregnancy rates. A prospective cohort study was performed at the University of Naples from June 2022 to December 2022. Ninety-three patients undergoing an IVF cycle with single embryo transfer (ET) (fresh or frozen) were enrolled in the study. Following ET, the catheter tip was inserted into brain heart infusion (BHI) medium under sterile conditions for culture. After 24h and 48h of incubation the microorganisms in the colonies were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Overall, 68 (73,92%) patients resulted positive for one or more microbes and 25 patients (26,08%) had no microbial growth. Across all participants, the four most important phyla were Firmicutes (87,76%), Proteobacteria (27,94%), Actinobacteria (10,29%) and Ascomycota (8,82%). Lactobacillus species, in particular, was significantly correlated with ongoing pregnancy rate (p=0,05). On the other hand, Staphylococcus subspecies (spp.) (p<0,05) and Enterobacteriaceae (p<0,001) were found to have a negative impact on the implantation rate. Detection of bacteria by culturomics from catheter tips used for embryo transfer has been shown to be a reliable method to detect pathogen growth. Endometrial microbiota testing in clinical practice could certainly offer a means to further improve diagnosis and treatment strategies in IVF patients.

Clinical outcome of different embryo transfer strategies after late rescue ICSI procedure: a 10-year total fertilisation failure cohort study

BackgroundLate rescue intracytoplasmic sperm injection (r-ICSI) has not been widely accepted as an alternative solution for unexpected total fertilisation failure (TFF) after in vitro fertilisation (IVF), due to the time-dependent in vitro deterioration of oocyte quality and endometrial growth not being synchronised with embryo development. This study aimed to evaluate the safety profile and effectiveness of freeze-all blastocyst transfer in combination with late r-ICSI.MethodsThis was a retrospective cohort study carried out at the Reproductive Centre of Peking University Third Hospital, Beijing, China. All participants received treatment between 2009 and 2019. 2,270 patients in the aggregate encountered unexpected TFF during 149,054 cycles of IVF and adopted a late r-ICSI procedure. Among these patients, 263 women did not have cleavage-stage embryos available for evaluation. The remaining patients were grouped according to different embryo transfer (ET) strategies (926 women in Group 1 underwent fresh ET, 365 women in Group 2 underwent freeze-all ET, 716 women in Group 3 experienced blastulation failure). Patients received different ET strategies after r-ICSI, with the main outcome measures included live birth rate (LBR), cumulative live birth rate (cLBR), and conservative cLBR.ResultsTFF occurred in 7.4% of all IVF cycles. Group 1 tended to be older at oocyte retrieval, with more infertile years, higher follicle-stimulating hormone (FSH) levels, higher gonadotropin consumption, and fewer oocytes retrieved. Group 2 exhibited considerably better LBRs following the first ET cycle (37.53% vs. 4.64%) and cLBRs (52.60% vs. 8.21%). After adjustment for covariates using binary logistic regression analyses, Group 2 still showed better obstetric performance in LBRs [OR:11.77, 95% CI (8.42–16.45)], cLBRs (OR:11.29, 95% CI (7.84–16.27)], and conservative cLBRs (OR:2.55, 95% CI (1.83–3.55)]. Additionally, the two groups showed similar miscarriage rates, whilst no new-borns with malformations or congenital diseases were reported.ConclusionsFreeze-all blastocyst stage ET serves as an optimal strategy to support late r-ICSI. However, for women with limited oocytes available for r-ICSI use, weighing the benefits against the costs of the procedure might be prudent before implementing in vitro blastulation.

Follicle Stimulating Hormone (FSH) as a Predictor of Decreased Oocyte Yield in Patients with Normal Anti-Müllerian Hormone (AMH) and Antral Follicle Count (AFC).

The purpose of the current study was to determine the utility of early follicular phase follicle-stimulating hormone (FSH) testing in patients undergoing in vitro fertilization (IVF). This was a retrospective review of patients from 2012 to 2015 at Mayo Clinic in Rochester, Minnesota, USA. Included subjects had a normal anti-Müllerian hormone (AMH) of 1 to 9 ng/ml and antral follicle count (AFC) of 10 to 29. Patients were stratified by FSH level when associated estradiol was less than 50 ng/ml. In total, 225 patients were categorized into three groups: high FSH (FSH ≥10 IU/L; n= 36), normal FSH (>5 IU/L and <10 IU/L; n=170), and low FSH (FSH ≤5 IU/L; n= 19). ANOVA and multiple logistic regression were used for statistical comparisons and for evaluation of the relationships between variables; significance level was set at <0.05. There were no significant differences in demographics, IVF cycle type, or peak estradiol level between the groups. Patients with a high basal FSH level had a similar clinical pregnancy rate and live birth rate compared to controls and patients with low FSH. High FSH level was associated with decreased follicular development (17 versus 22; p<0.01), oocyte yield (15 versus 18; p=0.02), and embryo yield (8 versus 10; p=0.04) despite higher total doses of gonadotropins. Patients with normal AMH and AFC levels could be further stratified into lower responders and starting doses of medications can be adjusted based on high basal FSH levels. Therefore, it is suggested to counsel patients on pregnancy outcomes which seem to be quite similar regardless of the FSH level.

Conventional follicular-phase ovarian stimulation vs. luteal-phase stimulation in suboptimal responders: a randomized controlled trial

To compare the oocyte yield between follicular-phase stimulation (FPS) and luteal-phase stimulation (LPS) in suboptimal responders. Prospective, randomized, crossover clinical trial. Forty-one patients with infertility according to the POSEIDON (Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number) criteria (1b/2b). Crossover study on 2 assigned ovarian stimulations that started randomly in the follicular or luteal phase. The invitro fertilization cycles were not consecutive but separated in time (45 days to 6 months). The random crossover design ensured that all subjects received the first treatment by chance. The primary objective was the number of cumulus-oocyte complexes retrieved in each cycle. Secondary objectives were number of metaphase II and fertilized oocytes, additional doses of recombinant follicle-stimulating hormone, and the duration of ovarian stimulation (days). The mean number of cumulus-oocyte complexes retrieved was similar between the FPS and LPS groups (7.5 ± 4.6 vs. 7.0 ± 4.1; 95% confidence interval [CI] for the mean, 5.8-8.7 vs. 5.6-8.3, respectively; the difference between means, -0.5; 95% CI, -1.8 to +1.5). Similarly, the mean number of metaphase II oocytes retrieved was not different between the FPS and LPS groups (5.4 ± 3.6 vs. 5.2 ± 2.8; 95% CI for the mean, 4.2-6.5 vs. 4.3-6.1, respectively; the difference between means, -0.2; 95% CI, -1.2 to +1.1). Moreover, the secondary objectives were similar between FPS and LPS groups. In this study, the oocyte yield in LPS did not increase in suboptimal responders compared with that in FPS when the onset of LPS was separated in time from FPS. NCT039393990 https://beta.clinicaltrials.gov/study/NCT03939390.

Role of Dydrogesterone for Luteal Phase Support in Assisted Reproduction.

Clinical outcomes of in vitro fertilization (IVF) have significantly improved over the years with the advent of the frozen-thawed embryo transfer (FET) technique. Ovarian hyperstimulation during IVF cycles causes luteal phase deficiency, a condition of insufficient progesterone. Intramuscular or vaginal progesterone and dydrogesterone are commonly used for luteal phase support in FET. Oral dydrogesterone has a higher bioavailability than progesterone and has high specificity for progesterone receptors. Though micronized vaginal progesterone has been the preferred option, recent data suggest that oral dydrogesterone might be an alternative therapeutic option for luteal phase support to improve clinical outcomes of IVF cycles. Dydrogesterone has a good safety profile and is well tolerated. Its efficacy has been evaluated in several clinical studies and demonstrated to be non-inferior to micronized vaginal progesterone in large-scale clinical trials. Oral dydrogesterone may potentially become a preferred drug for luteal phase support in millions of women undergoing IVF.

Increased serum IL-12 levels are associated with adverse IVF outcomes

Interleukin-12 (IL-12) is involved in the occurrence and development of many diseases, such as preeclampsia, intrauterine growth restriction, preterm labor, and recurrent pregnancy losses. This study aimed to determine whether a high serum level of IL-12 was associated with adverse in vitro fertilization (IVF) outcomes. Included infertile women with high serum IL-12 levels who underwent IVF cycles and infertile controls with pure tubal etiology. The impact of serum IL-12 on baseline and clinical characteristics, immune-related indicators, IVF laboratory, and pregnancy outcomes were compared. In addition, the correlation of follicular fluid IL-12 and serum IL-12 level and the role of IL-12 in apoptosis of granulosa cells (GCs) was investigated. Women with high serum IL-12 levels had lower numbers of retrieved oocytes, embryos, perfect and available embryos, lower rates of perfect and available embryos, and blastocyst formation. Additionally, significantly higher levels of serum Th1, Th2, and Th17-related cytokines were observed in women with high serum IL-12 levels than in the controls. Meanwhile, the follicular fluid IL-12 levels were positively correlated with serum IL-12 levels, and IL-12 promoted apoptosis of GCs in vitro. We concluded that women with serum high IL-12 levels may have adverse IVF outcomes, partly by promoting apoptosis of GCs. Therefore, early screening for cytokines, especially IL-12, and appropriate consultation for couples receiving IVF-ET should be considered. In addition, specific immune and inflammatory mechanisms associated with high serum IL-12 levels should be further explored.

Comparison of dydrogesterone plus progesterone gel with subcutaneous aqueous progesterone plus progesterone gel for luteal phase supplementation of subsequent in vitro cycle in women after previous cycle failure.

The luteal phase supplementation (LPS) of the in vitro fertilization (IVF) cycle is crucial to increase the chance of a live birth. There is no preferred progestogen for use in the general population. The optimal progestogen regimen in the event of prior IVF failure is unknown. The aim was to compare the live birth rate for dydrogesterone plus progesterone gel versus aqueous progesterone plus progesterone gel in LPS of the IVF cycle in women with at least one previous IVF failure. A prospective randomized single-center study enrolled women with at least one previous IVF failure undergoing another IVF cycle. Women were randomly assigned in a 1:1 ratio to 2 arms depending on LPS protocol: dydrogesterone (Duphaston®) + progesterone in vaginal gel (Crinone®) vs aqueous progesterone solution in subcutaneous injection (Prolutex®) + progesterone in vaginal gel (Crinone®). All women underwent fresh embryo transfer. The live birth rate with one prior IVF failure was 26.9% for D + PG vs 21.2% for AP + PG (p = 0.54), and with at least two IVF failures: 16% for D + PG vs 31.1% for AP + PG (p = 0.16). There were no significant differences in live birth rates between protocols, regardless of the number of prior IVF failures. In light of the evidence from this study that neither of the two LPS protocols is more effective in women with prior IVF failure, other factors, such as potential side effects, dosing convenience and patient preference, should be considered when choosing a treatment.

Validation of prognosis-based in vitro fertilization grant selection criteria

To validate a prognosis-based scoring system for invitro fertilization (IVF) grant allocation. Retrospective cohort study. A 501(c)(3) nonprofit foundation that awards donated IVF cycles and grants to those with demonstrated financial need. In contrast to lottery-based or subjective allocation systems, applications are scored according to medical prognostic criteria in addition to personal characteristics. Grant recipients from 2015 to2019. None. Live birth rate (LBR) and cumulative LBR (CLBR) among grant recipients were compared with 2019 Society for Assisted Reproductive Technology (SART) national averages. A total of 435 applications were reviewed, with 59 grants awarded for 51 autologous IVF cycles, 6 donor oocyte cycles, and 2 gestational carrier cycles, resulting in 39 live births after initial embryo transfer (LBR 61.9%) and 43 CLBRs (CLBR 72.9%). Among autologous cycles, the mean (±SD=3.9 years) age was 31.8 years, and LBR and CLBR were 62.8% and 68.6% vs. 28.2% and 37.1% among all autologous SART cycles, respectively. A subanalysis of grant recipients aged <35 years (n=39) revealed LBR and CLBR of 66.7% and 74.4% vs. 40.7% and 47.8% among autologous SART cycles aged <35 years, respectively. A scoring system incorporating medical criteria identified IVF grant applicants with a high likelihood of achieving a LB. Although most IVF grant programs select recipients through a lottery or personal characteristics, a prognosis-based scoring system should be considered to maximize LBR in a limited resource setting.

Dose Nomogram of Individualization of the Initial Follicle-Stimulating Hormone Dosage for Patients with Polycystic Ovary Syndrome Undergoing IVF/ICSI with the GnRH-Ant Protocol: A Retrospective Cohort Study.

For high responders with polycystic ovary syndrome (PCOS), there is no clear recommendation for the initial follicle-stimulating hormone (FSH) dosage to ensure an optimal number of retrieved oocytes and avoid ovarian hyperstimulation syndrome (OHSS). The aim of this study was to determine the ideal initial FSH dosage of in patients with PCOS undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) using the gonadotropin-releasing hormone antagonist (GnRH-ant) protocol to obtain the optimal number of retrieved oocytes and minimize the risk of OHSS. The data of 1898 patients with PCOS aged 20-40years from January 2017 to December 2020 were retrospectively analyzed to explore the factors related to the number of retrieved oocytes. Statistically significant variables were used to construct a dose nomogram and it was then validated using an independent cohort of patients with PCOS from January 2021 to December 2021. Multivariate analyses demonstrated that body mass index (BMI) was the most significant factor to predict the number of retrieved oocytes compared to body weight (BW) and body surface area (BSA). Among patients with PCOS aged 20-40years undergoing their first IVF cycles with the GnRH-ant protocol, age was not a significant predictor of the initial FSH dosage. We developed a nomogram based on BMI, basal FSH, basal luteinizing hormone (bLH), anti-Müllerian hormone (AMH), and antral follicle count (AFC) to calculate the ideal initial FSH dosage for patients with PCOS undergoing IVF/ICSI using the GnRH-ant protocol. In addition, low BMI and high bLH and AMH levels and AFC appear to be risk factors for OHSS. We clearly demonstrated that the initial FSH dosage for patients with PCOS undergoing IVF/ICSI with the GnRH-ant protocol may be calculated on the basis of the woman's BMI and ovarian reserve markers. The nomogram will help guide clinicians in the selection of the most appropriate initial FSH dose in the future.

Endometrial scratch injury in infertile women undergoing in vitro fertilization cycles: a systematic review and meta-analysis.

This study aimed to evaluate the effect of endometrial scratch injury (ESI) in infertile women undergoing in vitro fertilization (IVF). We screened MEDLINE, CENTRAL, EMBASE, Web of Science, and the Cochrane Central Register from inception to April 2023 using keywords related to endometrial scratch, implantation, infertility, and IVF. We included 41 randomized, controlled trials of ESI in IVF cycles (9084 women). The primary outcomes were the clinical pregnancy, ongoing pregnancy, and live birth rates. The clinical pregnancy rate was reported in all 41 studies. The odds ratio (OR) for the clinical pregnancy rate had an effect estimate of 1.34 with a 95% confidence interval (CI) of 1.14 to 1.58. The live birth rate was reported in 32 studies with 8129 participants. The OR for the live birth rate had an effect estimate of 1.30 with a 95% CI of 1.06 to 1.60. The multiple pregnancy rate was reported in 21 studies with 5736 participants. The OR for the multiple pregnancy rate had an effect estimate of 1.35 with a 95% CI of 1.07 to 1.71. ESI increases the clinical pregnancy, ongoing pregnancy, live birth, multiple pregnancy, and implantation rates in women undergoing IVF cycles.