Day Of Trigger Research Articles

Slightly Elevated Progesterone on HCG Trigger Day Has an Impact on Pregnancy Outcomes of Fresh Single Blastocyst Transfer Cycles Under an Early Follicular Phase Prolonged Protocol Cycle.

The effect of premature progesterone elevation on assisted reproductive technology has been debated. In different ovarian stimulation protocols, ovarian responses, and embryos transferred, conflicting results reside regarding the impact of elevated progesterone on pregnancy outcomes, according to previous studies. In addition, most studies have focused on significantly elevated progesterone levels, eg, above 1.5ng/mL, 1.75ng/mL, 2ng/mL. However, studies focusing on levels that are just slightly elevated are lacking, and some have concluded that such levels have no adverse effects on pregnancy outcomes. Clinical data of patients who underwent early follicular phase prolonged protocol cycle in vitro fertilization/intracytoplasmic sperm injection treatment were collected. Patients were divided into two groups according to progesterone level on the trigger day of human chorionic gonadotropin (HCG): Group 1: <1.0ng/mL and Group 2: 1.0-1.5ng/mL. Differences in baseline characteristics, ovulation promotion, and embryo culture, along with clinical pregnancy outcomes, were compared between the two cohorts. A total of 743 participants were included in this study, of which 587 were included in Group 1 and 156 were included in Group 2. In terms of pregnancy outcomes, Group 2 had a significantly lower clinical pregnancy rate and live birth rate per cycle than Group 1 (64.1% vs 75.7%, p <0.05; 63.5% vs 72.7%, p <0.05). After correction for maternal age, maternal body mass index, infertility duration, basal follicle-stimulating hormone, anti-Müllerian hormone, antral follicle count, total dose of gonadotropin, days of stimulation, and estradiol level on HCG trigger day, slightly elevated progesterone levels (P>1.0ng/mL) remained a risk factor for pregnancy failure in fresh single D5 blastocyst transfer under an early follicular phase prolonged protocol cycle. Slightly elevated progesterone levels on HCG trigger day may negatively affect pregnancy outcomes in early follicular phase prolonged protocol cycles.

Adverse impact of elevated serum progesterone and luteinizing hormone levels on the hCG trigger day on clinical pregnancy outcomes of modified natural frozen-thawed embryo transfer cycles.

The relationship between serum progesterone (P) and luteinizing hormone (LH) levels on the human chorionic gonadotropin (hCG) trigger day and the clinical pregnancy outcomes in modified natural frozen-thawed embryo transfer (mNC-FET) cycles are controversial. This was a retrospective study of 788 mNC-FET cycles. A smooth fitting curve and threshold effect analysis was performed to identify the effect of serum P and LH levels measured on the hCG day on the clinical pregnancy rate (CPR) and live birth rate (LBR) of mNC-FET cycles. The CPR and LBR decreased significantly when the LH level on the hCG day was greater than or equal to 32 IU/L. Further subgroup analysis showed that the CPR decreased significantly when the P level on the hCG day was equal to or greater than 1 ng/mL. When the P level was lower (< 1 ng/mL), the patients with an LH level greater than or equal to 32 IU/L had reduced CPR and LBR in mNC-FET cycles. Applying the hCG trigger on a day with a higher P level (≥ 1 ng/mL) leads to a decreased CPR and LBR. hCG administration with a higher LH level (≥ 32 IU/L) also leads to a decreased CPR and LBR in mNC-FET cycles when the P level is less than 1 ng/mL.

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

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

The effect of human chorionic gonadotropin day serum progesterone level on the live birth rate of fresh embryo transfer with GnRH antagonist protocols

Objective: To investigate the effect of human chorionic gonadotropin (HCG)day serum progesterone (P) level on the live birth rate (LBR) of fresh embryo transfer with GnRH antagonist protocols. Methods: Patients who underwent the first IVF/ICSI in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2020 were included for analysis. The patients with normal ovarian response with GnRH antagonist protocols were included (n=765). The receiver operating characteristic curve (ROC) was used to select the optimal cut-off value of serum P on HCG day (0.83 μg/L), and the included cycles were divided into two groups: P<0.83 μg/L (n=444) and P≥0.83 μg/L (n=321). The primary outcome measure was LBR. Secondary outcome measures included clinical pregnancy rate (CPR) and early miscarriage rate. The difference of the above indexes between the two groups was compared. Multivariate logistic regression model was used to analyze the effect of serum P level on LBR in fresh embryo transfer cycles. Results: The maternal ages in P<0.83 μg/L group and P≥0.83 μg/L group were (32.40±5.49) years and (32.53±5.51) yeas, respectively. The paternal ages were (33.35±6.34) years and (33.43±6.38) years, respectively of which, the difference was not statistically significant (P>0.05). The CPR in the P<0.83 μg/L group was 45.9% (n=204), which was significantly higher than that in the P≥0.83 μg/L group (37.1%) (n=119) (P=0.014). There was no significant difference in the early miscarriage rate between the two groups [14.2% (n=29) vs 14.3% (n=17), P=0.986]. The LBR in the P<0.83 μg/L group was significantly higher than that in the P≥0.83 μg/L group [36.3% (n=161) vs 28.0% (n=90), P=0.017]. By multivariate logistic regression model analysis, the maternal age, type of embryo transferred, number of embryos transferred, endometrial thickness on HCG day and serum P level on HCG day were independent risk factors of LBR. The adjust OR(95%CI) were 0.91(0.88-0.94), 2.36(1.04-5.35), 1.84(1.14-2.95), 1.16(1.07-1.25)and 0.63(0.44-0.89), all P<0.05. Conclusion: When the GnRH antagonist protocol is applied in the normal ovarian response population, as the serum P on the HCG trigger day≥0.83 μg/L, the CPR and LBR of fresh embryo transfer are decreased.

Study on the relationship between SlRTl and oxidative stress in aged patients undergoing in vitro fertilization and embryo transfer cycles

PurposeOxidative stress (OS) has been suggested to be involved in the pathogenesis of fertility reduction in aged patient. Silent Information Regulator 1 (SIRT1) is involved in antioxidant defense and also plays a role in regulation ovarian function. The purpose of this study was to evaluate SIRT1 and OS markers in follicular fluid (FF) and granulosa cells (GCs) for aged patient undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). MethodsThis single-center prospective cohort study was performed from May 2020 to October 2021, including 92 patients undergoing IVF/ICSI at authors’ institute. The patients were grouped by age, including group A (< 35 year, n = 28, age range 24-29), group B (35-40 year, n = 33, age range 35-40), and group C (> 40 year, n = 31, age range 41-47). The outcomes included in vitro fertilization and embryo transfer (IVF-ET) results, OS markers and SIRT1 levels. ResultsWomen in group B and group C had a significantly lower estradiol (E2) in the trigger day, retrieved oocytes, mature oocytes, two pronuclei (2PN) and Day3 available embryos than group A. Women in group C had a significantly lower implantation rate and clinical pregnancy rate than group A. The superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and SIRT1 levels were lower in FF of the group B and group C, whereas the malondialdehyde (MDA) level was higher than that in the group A. Moreover, the MDA levels were correlated negatively with SIRT1 (r = -0.422, P=0.001),while the SOD and GSH-Px was positively correlated with SIRT1 (r = 0.409, P = 0.001 and r = 0.526, P = 0.001). ConclusionsThe oxidative stress may be related to the decrease of SIRT1 in aged patients undergoing IVF-ET.

Oocyte Quality Assessment in Breast Cancer: Implications for Fertility Preservation.

The aim of this study was to evaluate the effects of breast cancer on the ovarian response and on oocyte quality following controlled ovarian hyperstimulation (COH). This retrospective case-control study evaluated the effects of breast cancer on the ovarian response and on the oocyte quality. Oncological patients with breast cancer undergoing controlled ovarian stimulation cycles for fertility preservation, and age- and date-matched controls undergoing COH for in vitro fertilization (IVF) for male or tubal factor infertility were included in the study. Two hundred and ninety-four women were enrolled: 105 affected by breast cancer and 189 healthy women in the control group. Both groups were comparable in terms of age, BMI, and AMH value. Maximal estradiol levels on the triggering day, duration of stimulation, total amount of gonadotropins administered, number of oocytes retrieved, rate of metaphase 2 oocyte production, and numbers of immature and dysmorphic oocytes were analyzed. Considering factors influencing the oocyte quality, such as age, BMI, AMH, duration of stimulation, E2 level on the triggering day, total FSH cumulative dose, stage, histotype, BRCA status, and hormone receptors, the univariate and multivariate analyses identified breast cancer as a risk factor for the presence of dysmorphic oocytes. The diagnosis of breast cancer does not seem to be associated with the impairment of the ovarian reserve, but is linked to a worsening oocyte quality.

E2 level > 2950 pg/ml on hCG trigger day is an independent predictor for birthweight loss of full-term singletons born after fresh embryo transfers in non-PCOS patients

BackgroundPrevious studies have demonstrated that the supraphysiological E2 level is negatively correlated with birthweight. However, the cut-off value of E2 level that significantly affects birthweight is unknown, and there is no definite conclusion regarding this level. Our study aimed to explore the threshold of the effect of E2 levels on birthweight.DesignA retrospective cohort study of 1846 samples was performed. All patients ≤42-years-old underwent autologous IVF cycles between August 1st, 2016 and April 30th, 2020. We categorized our data into four groups according to the E2 level: Group 1: ≤2000 pg/mL; Group 2: 2001–3000 pg/mL; Group 3: 3001–4000 pg/mL; and Group 4: > 4000 pg/mL.ResultsThe results of the multivariate regression analyses showed that when the E2 level was 3001–4000 pg/mL (adjusted β: − 89.64, 95% [CI]: − 180.29 to − 6.01; P = 0.0336) and greater than 4000 pg/mL (adjusted β: − 138.10, 95% [CI]: − 272.87 to − 10.33; P = 0.0181), weight loss was significant. Furthermore, the odds of full-term SGA were 1.40 times higher with E2 levels of 3001–4000 pg/mL (adjusted OR: 1.40, 95% [CI]: 1.090 to 3.18; P = 0.0256) and 2.55 times higher with E2 > 4000 pg/mL (adjusted OR: 2.55, 95% [CI]: 1.84 to 3.86; P = 0.0063) compared to the reference group. It can also be seen from the adjusted curves and the threshold effects that when the E2 level > 2950 pg/mL and > 3121 pg/mL, the incidence of SGA increased and the birthweight decreased, respectively.ConclusionsOur data suggest that E2 levels > 2950 pg/mL is an independent predictor for greater odds of full-term SGA singletons born after fresh embryo transfer.

Elevated serum progesterone levels on the hCG trigger day have a negative impact on the live birth rate in the first fresh IVF-ET cycle

To investigate whether there is a relationship between elevated serum progesterone (PROG) on the hCG trigger day and the live birth rate (LBR) in IVF/ICSI cycles, the retrospective analysis was carried out from the patients undergoing the first ART cycles throughout 2016. The PROG levels were measured on the hCG trigger day. The LBR, clinical pregnancy rate (CPR), implantation rate (IR) and other parameter rate values were compared among the three different PROG elevations. A total of 2550 IVF/ICSI cycles fulfilling all the inclusion and exclusion criteria were selected. Finally, three groups [PROG <0.40 ng/mL, 0.40 ≤ PROG < 1.5 ng/mL, PROG ≥ 1.5 ng/mL] were categorised based on the serum PROG levels. LBR, CPR and IR declined as the PROG value increased, while there was no difference in the embryo utilisation rates. Serum PROG levels on the day of hCG administration were negatively associated with the LBR, even in ETs with a good prognosis. Impact Statement What is already known on this subject? The clinical effects of PROG are still controversial. Some studies have confirmed that there was not too much association between premature elevation of PROG and live birth, some are still convincing that there is a negative correlation and will result in ART cycles of pregnancy and LBR reduction. What do the results of this study add? Our data substantiated that the high serum PROG level had the lowest LBR, IR and CPR, but the embryo utilisation rate may not have too much to do with the elevated PROG. What are the implications of these findings for clinical practice and/or further research? This study further strengthens the negative impact of elevated PROG levels on pregnancy outcomes, and suggests that frozen thawed embryo transfer appears to be a reasonable and advantageous approach for this subset of patients.

Estimation of follicular growth—widely used, seldom studied

We assessed whether estimation of follicular growth, rather than actual measurement of follicular size on the day of hCG trigger, affected pregnancy rates in intrauterine insemination (IUI) cycles. Patient and cycle characteristics were extracted from an existing database. Comparisons were made between the pregnant (defined as a positive beta hCG) and non-pregnant groups for the following variables: patient’s age, number of previous IUI cycles, type of ovarian stimulation, endometrial thickness, number of follicles measuring 14 mm and above, pre and post wash sperm parameters, cycle day when IUI was done and number of days between last ultrasound scan and ovulation trigger. A total of 7302 cycles were included in the final analysis. In 4055 cycles (55.5%) the hCG trigger was on the day of the last ultrasound, in 2285 cycles (31.3%) the hCG trigger was 1 day after the last ultrasound, in 850 (11.6%) it was 2 days after the last ultrasound and in 112 (1.5%) it was 3 or more days after the last ultrasound. Sperm parameters, younger maternal age, and the number of follicles above 14 mm were all associated with pregnancy. No association was found between positive pregnancy test rates and the time from last ultrasound to hCG trigger. Planning IUI based on the estimation of follicular growth 1–4 days before trigger, does not affect pregnancy rates.

The role of peak serum estradiol level in the prevention of multiple pregnancies in gonadotropin stimulated intrauterine insemination cycles

The objective was to assess whether the measurement of serum estradiol (E2) level on trigger day in controlled ovarian stimulation with intrauterine insemination (COS-IUI) cycles helps lower the multiple pregnancy (MP) rate. We performed a unicentric observational study. We included all patients who underwent COS-IUI and had a subsequent clinical pregnancy (CP) between 2011 and 2019. Our main outcome measure was the area under Receiver-Operating Characteristic (ROC) curve. We included 455 clinical pregnancies (CP) obtained from 3387 COS-IUI cycles: 418 singletons, 35 twins, and 2 triplets. The CP, MP, and live birth rates were respectively 13.4%, 8.1% and 10.8%. The area under ROC curve for peak serum E2 was 0.60 (0.52–0.69). The mean E2 level was comparable between singletons and MP (260.1 ± 156.1 pg/mL vs. 293.0 ± 133.4 pg/mL, p = 0.21, respectively). Univariate and multivariate logistic regression analysis showed that E2 level was not predictive of MP rate (aOR: 1.13 (0.93–1.37) and 1.06 (0.85–1.32), respectively). Our study shows that, when strict cancelation criteria based on the woman’s age and follicular response on ultrasound are applied, the measurement of peak serum E2 levels does not help reduce the risk of MP in COS-IUI cycles.

Analysis of relative factors and prediction model for optimal ovarian response with gonadotropin-releasing hormone antagonist protocol.

To explore the relative factors for best ovarian response in patients undergoing assisted reproductive technology with the gonadotropin-releasing hormone antagonist protocol and to establish a nomogram prediction model of ovarian response. A retrospective cohort analysis of the clinical data of 1,944 patients who received assisted reproductive treatment in the Center for Reproductive Medicine of Fujian Maternity and Child Health Hospital from April 1, 2018, to June 30, 2020. According to the number of oocytes obtained, there were 659 cases in the low ovarian response group (no more than five oocytes were retrieved), 920 cases in the normal ovarian response group (the number of retrieved oocytes was >5 but ≤18), and 365 cases in the high ovarian response group (>18 oocytes retrieved). Independent factors affecting ovarian responsiveness were screened by logistic regression, which were the model entry variables, and a nomogram prediction model was established based on the regression coefficients. There were statistically significant differences in age, anti-Mullerian hormone, antral follicle count, the diagnosis of endometriosis, decreased ovarian reserve, polycystic ovary syndrome, basal follicle-stimulating hormone and basal luteinizing hormone among the three groups (P < 0.001). Multifactorial stepwise regression analysis showed that female age (0.95 [0.92-0.97], P = 0.000), decreased ovarian reserve (0.27 [0.19-0.38]), P = 0.000), endometriosis (0.81 [0.56-0.86], P = 0.000), antral follicle count (1.09 [1.06-1.12], P = 0.000), basal follicle-stimulating hormone (0.90 [0.85-0.96], P = 0.001), Anti-Mullerian hormone (1.19 [1.13-1.26], P= 0.000) and luteinizing hormone on trigger day (0.73 [0.66-0.80], P= 0.000), were independent factors for the occurrence of different ovarian responses during ovarian hyperstimulation. The predictive model of ovarian responsiveness was constructed based on the above factors, and the model was verified with 589 patients' data from July 1, 2020, to December 31, 2020, at this center. The predicted ovarian response (number of eggs obtained) of a total of 450 patients was consistent with the actual results, with a coincidence degree of 76.4%, and the consistency index of the model is 0.77. The nomogram model was successfully developed to effectively, intuitively, and visually predict the ovary reactivity in the gonadotropin-releasing hormone antagonist protocol and provide guidance for clinical practice.

Association between oocyte retrieval technique and number of oocytes retrieved.

To assess if there is an optimal oocyte retrieval (OR) technique to retrieve a maximum number of oocytes and mature oocytes (MII). Retrospective cohort study in which nine physicians completed a survey on OR techniques. Number of oocytes/follicle cohort, MIIs/follicle cohort, and MIIs/oocytes retrieved (%MII) were assessed for each technique for patients undergoing OR from 3/2013 to 7/2019. Data were stratified by number of follicles on ultrasound on day of trigger (< 6, 6-10, > 10). Patient demographics were equivalent between techniques. For < 6 follicles, three techniques resulted in significantly fewer oocyte/follicle (0.97 ± 0.48, 0.95 ± 0.66, and 0.90 ± 0.41) compared to the top-performing technique (TPT) (1.11 ± 0.55). For 6-10 follicles, two techniques resulted in significantly fewer oocyte/follicle (0.95 ± 0.39 and 0.93 ± 0.35) compared to the TPT (1.06 ± 0.42). A different technique had higher %MII (0.77 ± 0.19) compared to two techniques (0.74 ± 0.21 and 0.72 ± 0.22). For > 10 follicles, two techniques resulted in significantly fewer oocyte/follicle (1.01 ± 0.42 and 1.07 ± 0.40) compared to the TPT (1.15 ± 0.41). These two techniques also resulted in fewer MII/follicle (0.75 ± 0.33 and 0.81 ± 0.34 vs. 0.87 ± 0.34). There was no consistent TPT across follicle number groups or for all outcome variables. There does not appear to be a clear TPT, even for patients with few follicles. Providers who perform OR in a similar fashion to physicians at our institution should feel confident that those techniques obtain equivalent oocyte yields.

Chromosomal polymorphisms have no negative effect on reproductive outcomes after IVF/ICSI-ET/FET

The present study aimed to explore whether chromosomal polymorphisms (CPs) have negative effects on reproductive outcomes of in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET)/frozen-thawing embryo transfer (FET)? We conducted a retrospective study consisting of 21,867 assisted reproductive technology treatment cycles, among which, fresh embryo transfer cycles accounted for 10,400, and the rest were FET cycles. According to karyotype of CPs, the former was grouped as: group 1 (male carrier, n = 425), group 2 (female carrier, n = 262), and group 3 (couple without CPs, n = 9713). Accordingly, FET cycles were divided into 3 groups: group 4 (male carrier, n = 298), group 5 (female carrier, n = 311), and group 6 (couple without CPs, n = 10,858). The embryo implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), and early miscarriage rate (EMR) were compared among the groups. In fresh embryo transfer cycles after IVF/ICSI, there were no significant differences in the infertility duration, BMI, basal FSH, no. of oocyte, no. of 2PN, endometrial thickness on trigger day, serum E2, P, and LH level on trigger day (P > 0.05). The female age, no. of 2PN embryo cleavage, top-quality embryo, and no. of embryo transferred were significantly different among groups (P < 0.05). The IR was 38.8%, 36.2%, and 34.0% in groups 1, 2, and 3, respectively. The CPR was 55.1%, 52.3%, and 49.7%, respectively. The LBR was 36.9%, 37.4%, and 36.4%, respectively. The CPR and LBR showed no significant differences among groups. The IR was lower and the EMR was higher in group 3 than those of groups 1 and 2. Binary logistic regression analysis indicated that female age, no. of embryo transferred, EMT, LH, and P on the trigger day were independently factors associated with CPR. Besides, no. of embryo transferred, and EMT on trigger day were associated with LBR, while the CPs was not related with CPR and LBR after IVF/ICSI-ET. In FET cycles, the infertility duration was similar (P > 0.05), but the female age, BMI, no. of embryo transferred were significantly different among groups (P > 0.05). The IR was 24.3%, 23.6% and 22.3% in group 4, 5, and 6, receptivity. The CPR was 31.8%, 30.9%, and 30.0%, the LBR was 23.8%,26.3%, and 23.8%, while the EMR was 12.6%, 13.1%, 14.4%, respectively. The IR, CPR, EMR, and LBR showed no significant differences among groups (P > 0.05). Binary logistic regression analysis indicated that female age, infertility duration, and no. of embryo transferred were independently factors affecting CPR and LBR after FET. The CPs were not associated with CPR and LBR after FET. The results suggested that uniparental carrying of CPs have no effects on the reproductive outcomes after IVF/ICSI-ET/FET. However, it is not clear whether both parents carrying CPs would affect pregnancy outcome.

Optimal lead follicle size in letrozole human menopausal gonadotrophin intrauterine insemination cycles with and without spontaneous LH surge

Research questionWhat is the optimal lead follicle size in letrozole, human menopausal gonadotrophin and intrauterine insemination (IUI) cycles with and without spontaneous LH surges? DesignThis retrospective cohort study included 3797 letrozole HMG IUI cycles between January 2010 and May 2021. All cycles were divided into two groups: the HCG trigger group (trigger day LH ≤15 mIU/ml) and the spontaneous LH surge group (trigger day LH >15 mIU/ml). These two groups were subdivided into smaller groups based on the diameter of the follicles. The primary outcome measure was clinical pregnancy rate. Logistic regression analysis was conducted to explore other risk factors. ResultsIn the HCG trigger group, the clinical pregnancy rate varied significantly, with rates of 20.8%, 14.9% and 11.8% for the 16.1–18.0, 18.1–20.0 and 20.1–22.0 mm groups, respectively (P = 0.005). In the spontaneous LH surge group, the pregnancy rate of follicles within 14.1–16.0 mm was significantly higher than that of follicles within 20.1–22.0 mm (adjusted OR 0.533, 95% CI 0.308 to 0.923, P = 0.025). Also, patients with two lead follicles were 2.569 times more likely to achieve a clinical pregnancy than those with only one lead follicle (adjusted OR 2.569, 95% CI 1.258 to 5.246, P = 0.010). The duration of infertility was also found to be a common influencing factor in both groups. ConclusionsThe optimal lead follicle size was between 16.1 and 18.0 mm in HCG-triggered letrozole HMG IUI cycles. If the lead follicle size is relatively small (14.1–18.0 mm) when a spontaneous LH surge occurs, there is no need to cancel the IUI cycle.

Evaluation of The Effect of Letrozole in the Ovarian Hyperstimulation Syndrome Prevention in Participants at Risk of Treatment with Ovulation-Stimulating Drugs:A Randomized Controlled Trial.

This study aims to evaluate the effect of Letrozole (LE) in reducing ovarian hyperstimulation syndrome (OHSS) in high-risk participants with polycystic ovary syndrome (PCOS) treated with In vitro fertilization (IVF). This study was a randomized clinical trial in which participants were randomly divided into two groups (n= 25 per group). Based on GnRH-antagonist protocol, recombinant follicle-stimulating hormone 150 units/day subcutaneously and human menopausal gonadotropin 75 units/ day intramuscularly used from day 2 of the menstrual cycle. In the study group, Letrozole 5 mg daily was added simultaneously with gonadotropin during the first five days of the IVF cycle and in the control group placebo was added. There were statistically significant differences among the groups in terms of Estradiol level on Trigger Day (p= 0.04). The total days of stimulation and cumulative Gonadotropin dose were significantly lower in the Letrozole group (p= 0.00). There were no significant differences between the groups in terms of the number of oocytes retrieved, numbers of implanted embryos, and clinical pregnancy rates (p-value> 0.05). There was only one moderate case in the intervention group and 9 moderate symptoms in the control group (p= 0.04). Administration of Letrozole with GnRH antagonist protocol, conventional protocol in PCOS cases in IVF cycle, had a significant effect on reducing the incidence of OHSS. So, if the future studies prove LE co-administration may lessen the incidence of OHSS, LE will be a highly potent drug for preventing OHSS in PCOS cases.

Comparison of blastocyst euploidy rates following luteal versus follicular phase stimulation in a GnRH antagonist protocol: a prospective study with repeated ovarian stimulation cycles.

Is there any difference in the mean number of euploid embryos following luteal phase start (LS) and follicular phase start (FS) of ovarian stimulation? The mean number of euploid blastocysts is equivalent independent of whether the inseminated oocytes are derived from FS or LS. Starting ovarian stimulation at any time of the cycle ('random-start') is commonly used for emergency fertility preservation in cancer patients. A few retrospective studies have been published evaluating LS in women undergoing ovarian stimulation in the context of IVF, but there is a lack of robust data on the comparative efficacy of LS versus FS.Although 'random start' is commonly used in cancer survivors, few retrospective and uncontrolled studies have been published evaluating luteal phase stimulation in women undergoing ovarian stimulation in the context of IVF. Owing to this evident lack of robust data on the efficacy of LS, guidelines typically recommend the LS approach only for medical reasons and not in the context of IVF. This is a prospective, equivalence study, with repeated stimulation cycles, conducted between May 2018 and December 2021. Overall, 44 oocyte donors underwent two identical consecutive ovarian stimulation cycles, one initiated in the FS and the other in the LS. The primary outcome of the study was to evaluate whether FS and LS in the same patient would result in equivalent numbers of euploid embryos following fertilization of oocytes with the same sperm sample. Overall, 44 oocyte donors underwent two consecutive ovarian stimulation protocols with 150 μg corifollitropin alpha followed by 200 IU recombinant FSH (rFSH) in a fixed GnRH antagonist protocol. The only difference between the two cycles was the day of initiation of ovarian stimulation, which was in the early follicular phase (FS) in one cycle, and in the luteal phase (LS) in the other. Forty-four oocyte recipients participated in the study receiving a mean of six metaphase II (MII) oocytes from each stimulation cycle (FS and LS). All MIIs were inseminated with the corresponding recipient's partner sperm (which had been previously frozen) or donor sperm, in order to safeguard the use of the same sample for either the FS or LS. Following fertilization and blastocyst culture, all generated embryos underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuploidy). FS resulted in a significantly shorter duration of ovarian stimulation (difference between means (DBM) -1.05 (95% CI -1.89; -0.20)) and a lower total additional dose of daily rFSH was needed (DBM -196.02 (95% CI -319.92; -72.12)) compared with LS. The donors' hormonal profile on the day of trigger was comparable between the two stimulation cycles, as well as the mean number of oocytes (23.70 ± 10.79 versus 23.70 ± 8.81) (DBM 0.00 (95% CI -3.03; 3.03)) and MII oocytes (20.27 ± 9.60 versus 20.73 ± 8.65) (DBM -0.45 (95% CI -2.82; 1.91)) between FS and LS cycles, respectively. Following fertilization, the overall blastocyst formation rate was 60.70% with a euploid rate of 57.1%. Comparisons between the two stimulation cycles did not reveal any significance differences in terms of fertilization rates (71.9% versus 71.4%), blastocyst formation rates (59.4% versus 62%) and embryo euploidy rates (56.9 versus 57.3%) for the comparison of FS versus LS, respectively. The mean number of euploid blastocysts was equivalent between the FS (1.59 ± 1.30) and the LS (1.61 ± 1.17), (DBM -0.02 (90%CI -0.48; 0.44)). The study was performed in young, potentially fertile oocyte donors who are patients with high blastocyst euploidy rates. Although results may be extrapolated to young infertile women with good ovarian reserve, caution is needed prior to generalizing the results to infertile women of older age. The current study provides evidence that initiation of ovarian stimulation in the luteal phase in young potentially fertile women may result in a comparable number of oocytes and comparable blastocyst euploidy rates compared with follicular phase stimulation. This may imply that in case of a freeze-all protocol in young patients with good ovarian reserve, clinicians may safely consider initiation of ovarian stimulation during the luteal phase. This research was supported by an unrestricted grant from MSD/Organon. N.P.P. has received Research grants and honoraria for lectures from: Merck Serono, MSD/Organon, Ferring Pharmaceuticals, Besins Intenational, Roche Diagnostics, IBSA, Theramex, Gedeon Richter. F.M., E.C., M.R. and S.G. declared no conflict of interests. The study was registered at Clinical Trials Gov (NCT03555942).

Vacuolization in embryos on days 3 and 4 of in vitro development: Association with stimulation protocols, embryo development, chromosomal status, pregnancy and neonatal outcomes.

Is vacuolization in embryos on Days 3 and 4 associated with parent-related factors, stimulation protocols, embryo development, embryo ploidy, pregnancy and neonatal outcomes? This is a retrospective cohort study that comprised 5,703 embryos from 611 patients who underwent preimplantation genetic testing and time-lapse monitoring of their embryos from August 2017 to September 2021. Embryo vacuolization on Days 3 and 4 is associated with the LH level on the day of the hCG trigger and the number of retrieved oocytes. Compared to vacuole-negative embryos, the rates of blastocyst formation and good-blastocyst formation was significantly lower in vacuole-positive embryos. We observed no significant difference in the rates of euploidy, implantation, ongoing pregnancy, and live birth between vacuole-positive and vacuole-negative embryos. In vacuole-positive embryos, the embryos of which the vacuole-positive blastomeres were involved in embryo compaction exhibited significantly higher mosaicism rate compared with those of which the vacuole-positive blastomeres were not involved in embryo compaction. Vacuolization in embryos on Days 3 and 4 is associated with reduced blastocyst formation rate and high-quality blastocyst rate. Blastocysts had a low mosaicism rate if the vacuole-containing cells were rejected in compaction process, which supports the hypothesis that exclusion of abnormal blastomeres from compaction is a self-correction mechanism.

Low-grade inflammation is negatively associated with live birth in women undergoing IVF

Research questionIs low-grade inflammation, detected by C-reactive protein (CRP), a marker of IVF outcome addressing both blastocyst quality and pregnancy outcome? DesignThis sub-study of a multicentre randomized controlled trial included 440 women undergoing IVF treatment with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. Serum CRP was measured on cycle day 2–3 (baseline) and on the day of ovulation triggering. The association between CRP concentrations and reproductive outcomes (number of retrieved oocytes, number of good-quality blastocysts, pregnancy, pregnancy loss and live birth), were analysed, adjusting for relevant confounders. ResultsA negative association was found between higher baseline CRP concentrations and live birth rate (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.62–0.96, P = 0.02) and higher CRP concentrations at baseline were associated with pregnancy loss among women who conceived (OR 1.37, 95% CI 1.07–1.76, P = 0.01). When testing for a specific cut-off, CRP concentrations above 2.34 (the highest quartile) were more likely to be associated with pregnancy loss (P = 0.02) and a lower chance of live birth (P = 0.04) compared with the lowest quartile. No associations were found between CRP concentrations and pregnancy outcomes on the day of ovulation triggering, and there were no associations between CRP concentrations and the number of good-quality blastocysts. ConclusionsHigher CRP concentrations at cycle day 2–3, before starting ovarian stimulation, are negatively associated with chance of live birth, possibly because of an increased risk of pregnancy loss. No association was found between the number of good-quality blastocysts and CRP concentration. More studies are needed to investigate the impact of low-grade inflammation.

IMPACT OF CHRONIC PROGESTERONE ELEVATION (PRE-TRIGGER) ON FROZEN EMBRYO TRANSFER OUTCOMES

Prior studies showed that elevated progesterone (EP) on day of ovulation trigger during controlled ovarian hyperstimulation is associated with decreased pregnancy rates in fresh but not frozen embryo transfers (FET). Although this effect of EP on day of trigger has been established, few studies have investigated the effect that duration of EP has on outcomes. In this study, we aimed to determine the effect of chronic EP (i.e. EP sustained for 1, 2 , and ≥3 days prior to trigger) on clinical pregnancy (CPR) and livebirth rates (LBR) following FET.

HIGH FOLLICLE STIMULATING HORMONE (FSH) LEVEL ON THE DAY OF TRIGGER IMPACTS NEGATIVELY THE EUPLOIDY RATE OF BLASTOCYSTS

To evaluate, in ovarian stimulation cycles for IVF/ICSI, the impact of the systemic FSH level on the Day of Trigger (DoT) on the ploidy rate of the blastocyst cohort.