Lower Live Birth Rates Research Articles

The impact of estradiol on pregnancy outcomes in letrozole-stimulated frozen embryo transfer cycles

ObjectiveTo assess the impact of low estradiol (E2) levels in letrozole-stimulated frozen embryo transfer (FET) cycles on pregnancy and neonatal outcomes.DesignRetrospective cohort.SettingUniversity-affiliated fertility center.Patient(s)All patients who underwent letrozole-stimulated FET cycles from January 2017 to April 2020 (n = 217). The “Low E2” group was defined as those with E2 serum levels on the day of trigger <10th percentile level (E2 <91.16 pg/mL, n = 22) and the “Normal E2” group was defined as those with E2 serum levels ≥10th percentile level (E2 ≥91.16 pg/mL, n = 195).Intervention(s)None.Main Outcome Measure(s)Pregnancy outcomes including rates of clinical pregnancy, clinical miscarriage, and live birth. Neonatal outcomes including gestational age at delivery, birth weight, and Apgar score.Result(s)The mean ± SD estradiol level was 66.8 ± 14.8 pg/mL for the “Low E2” group compared with 366.3 ± 322.1 pg/mL for the “Normal E2” group. There were otherwise no substantial differences in cycle characteristics such as endometrial thickness on the day of ovulation trigger and progesterone levels in early pregnancy. The “Low E2” group had a significantly higher clinical miscarriage rate (36.4% vs. 8.8%, adjusted odds ratio 8.06) and lower live birth rate (31.8% vs. 57.9%, adjusted odds ratio 0.28). Neonatal outcomes such as gestational age at delivery, mean birth weight, Apgar scores, and incidence of newborn complications were not clinically different between the groups.ConclusionLow E2 levels were associated with a significantly higher miscarriage rate and lower live birth rate, suggesting that E2 levels in the follicular phase may have an effect on cycle outcomes. Given the rise in use of FET, further studies are needed to confirm our findings and understand the mechanisms.

High Serum Anti-Müllerian Hormone Concentrations Are Associated With Poor Pregnancy Outcome in Fresh IVF/ICSI Cycle but Not Cumulative Live Birth Rate in PCOS Patients.

ObjectiveTo investigate the association between baseline serum Anti-Müllerian hormone (AMH) levels and IVF/ICSI outcomes in women with polycystic ovary syndrome (PCOS).DesignRetrospective study.SettingReproductive medicine center in a hospital.Population2436 PCOS patients (Rotterdam criteria) who underwent their first fresh IVF/ICSI cycles were divided into three groups on the basis of the <25th (Group 1, n=611), 25 to 75th (Group 2, n=1216), or >75th (Group 3, n=609) percentile of baseline serum AMH level.Intervention(s)Baseline serum AMH levels measured on the 2-3 days of spontaneous menstrual cycle before IVF/ICSI treatment.Main Outcome Measure(s)Live birth rate (LBR), cumulative live birth rate (CLBR), clinical pregnancy rate (CPR), and normal fertilization rate (FR).Result(s)The LBR, CPR, and FR were significantly increased in Group 1 than Group 2 and Group 3, however, CLBR was similar between the three groups. The LBR were 46.6%, 40.5%, and 39.4% in Group 1, Group 2, and Group 3 respectively. The CPR were 53.0%, 47.0%, and 45.5%, respectively. The FR was highest in Group 1 (61.7%, P<0.05), but there was no uniform reverse trend with the AMH level. CLBR were 68.7%, 70.4%, and 71.3%, respectively. Although women in Group 1 were older (p < 0.05) and had higher body mass index (BMI) (p < 0.05), binomial logistic regression analysis used age, BMI, FSH, and AMH as independent variables indicated that only AMH was significantly associated with LBR and CPR. Nevertheless, binomial logistic regression analysis used age, BMI, FSH, AMH, and the number of retrieved oocytes as independent variables indicated that only the number of retrieved oocytes was significantly correlated with CLBR. After stratifying by age, the negative relationship between baseline AMH level and LBR and CPR remained only in the patients <30 years old.Conclusion(s)Higher baseline AMH level in PCOS women resulted in lower LBR, CPR, and FR but did not influence CLBR.

Pregnancies in women with moderate and severe pulmonary hypertension remain challenging: A single-center experience in East China.

To determine the outcomes in women with pulmonary hypertension (PH) and determine the factors related to adverse outcomes. Data from 684 women with PH admitted to the Affiliated Renji Hospital from January 2001 to December 2020 were collected. Outcomes were compared based on the causes and severity of PH. The overall mortality was 2.8%, decreasing from 6.6% in 2001-2005 to 1.7% in 2016-2020 (P=0.10). Idiopathic PH had the highest mortality (35.3%) and the lowest live birth rate (82.4%). Mortality was similar between moderate and severe PH (5.3% versus 9.7%), but the live birth rate was much lower in severe PH (78.6% versus 89.9%). Hypoxemia and vaginal birth were risk factors of maternal death (odds ratio [OR] 35.28, 95% confidence interval [CI] 1.42-878.75; OR 850.86, 95% CI 5.67-127606.74, respectively). General anesthesia was a risk factor in the univariate analysis (OR 12.07, 95% CI 3.72-39.15) but was not significant in the multivariate analysis (P=0.16). The mortality rate in this retrospective study was lower than that previously reported. Pregnancy is safe in mild PH but still has a high risk of complications in moderate and severe PH. Hypoxemia is a risk factor for maternal death, but cesarean section may be a protective factor.

Early embryo morphokinetics is a better predictor of post-ICSI live birth than embryo morphology: speed is more important than beauty at the cleavage stage

Given the importance of embryo developmental competence assessment in reproductive medicine and biology, the aim of this study was to compare the performance of fertilization and cleavage morphokinetics with embryo morphology to predict post-ICSI live birth. Data from embryos cultured in a time-lapse microscopy (TLM) incubator and with known live birth outcomes (LB: embryos achieving live birth, n = 168; NLB: embryos not achieving live birth, n = 1633) were used to generate receiver operating characteristic (ROC) curves based on morphokinetic or morphological scores, and the respective areas under the curve (AUC) were compared. The association between live birth and 12 combinations of four morphokinetic quality degrees (A-D) with three morphological quality degrees (A-C) was assessed using multivariate analysis. Morphokinetic parameters from tPNa to t8 were reached earlier in LB compared with NLB embryos. The ROC curve analysis indicated that morphokinetic information is more accurate than conventional morphology to predict live birth [AUC = 0.64 (95% CI 0.58-0.70) versus AUC = 0.58 (95% CI 0.51-0.65)]. The multivariate analysis was in line with AUCs, revealing that embryos with poor morphokinetics, independently of their morphology, provide lower live birth rates (P < 0.001). A considerable percentage of embryos with top morphology presented poor morphokinetics (20.10%), accompanied by a severely reduced live birth rate in comparison with embryos with top morphology and morphokinetics (P < 0.001). In conclusion, TLM-derived early morphokinetic parameters were more predictive of live-birth achievement following ICSI than conventional morphology.

Low Serum LH Levels During Ovarian Stimulation With GnRH Antagonist Protocol Decrease the Live Birth Rate After Fresh Embryo Transfers but Have No Impact in Freeze-All Cycles.

ObjectiveTo explore the association between serum LH levels and the cumulative live birth rate (CLBR) within one complete cycle, and the impact of serum LH levels on the live birth rate (LBR) after the initial embryo transfer (ET) considering different ET strategies (fresh or freeze-all).DesignA retrospective cohort study.SettingUniversity-affiliated reproductive center.Patients1480 normogonadotrophic women who underwent COS with GnRH antagonist protocol for the first IVF/ICSI attempt.Intervention(s)The sample was stratified into low and higher LH groups according to serum LH peak levels of <4 (Group A) and ≥4 IU/L (Group B) during COS. Patients were also sub-grouped into conventional fresh/frozen ET cycles and freeze-all cycles.Main outcome measure(s)The LBR after the initial embryo transfer and the CLBR within one complete cycle.Secondary outcome measure(s)The numbers of day-3 high-quality embryos, the numbers of embryos available, and the other pregnancy outcomes after the initial ET.Result(s)In the whole cohort, the CLBRs decreased significantly in the low (63.1% vs. 68.3%, P=.034) LH group compared to the higher LH group. Subgroup analysis revealed that patients with low LH levels had lower LBR after fresh ET (38.0% vs. 51.5%, P=.005) but comparable LBR after the first frozen-thawed ET (FET) in freeze-all cycles (49.8% vs. 51.8%, P=.517) than patients with higher LH peak levels. Likewise, patients with low LH levels had lower CLBR for conventional fresh/frozen ET cycles (54.8% vs. 66.1%, P=.015) but comparable CLBR for the freeze-all cycles (66.8% vs. 69.2%, P=.414) than those with higher LH levels. Following confounder adjustment, multivariable regression analyses showed that low LH level was an independent risk factor for the CLBR in the whole cohort (odds ratio (OR): 0.756, 95% confidence interval (CI): 0.604-0.965, P=.014) and in patients who underwent the conventional ET strategy (OR: 0.596, 95% CI: 0.408-0.917, P=.017). Moreover, the adverse impact of low LH levels on LBRs maintained statistically significant after fresh transfers (OR: 0.532, 95% CI: 0.353-0.800, P=.002) but not after the first FETs in freeze-all cycles (OR: 0.918, 95% CI: 0.711-1.183, P=.508).Conclusion(s)In comparison with higher LH levels, low LH levels decrease the CLBRs per oocyte retrieval cycle for normogonadotrophic women who underwent COS using GnRH antagonists. This discrepancy may arise due to the significant detrimental effect of low LH levels on the LBRs after fresh embryo transfers.

Predictive value of cytoplasmic granulation patterns during in vitro fertilization in metaphase II oocytes: Part I, poor-prognosis patients

To determine whether 4 cytoplasmic granulation patterns of human metaphase II oocytes have a predictive value for invitro fertilization outcomes. A retrospective cohort study. An academically affiliated private clinical infertility and research center. A total of 2,690 consecutive fresh autologous oocytes collected from women aged 41.2 ± 5.0 years between 2017 and 2019. Determination of granulation pattern in every oocyte during intracytoplasmic sperm injection as fine, central, dispersed, and newly introduced uneven granulations. Fertilization outcomes (2 pronuclei [2PN], <2PN, and >2PN rates), pregnancy, and live birth rates for different granulation patterns at different ages. Fine granulation produced the highest 2PN rate, followed by central, uneven, and dispersed granulation (91.8%, 83.9%, 77.9%, and 54.8%, respectively). Differences in fertilization were surprisingly relatively independent of age and other variables. Overall, compared with fine granulation, dispersed granulation resulted in lower pregnancy rates (4.6% vs. 10.7%) and known-outcome analysis (1.3% vs. 5.6%) as well as lower live birth rates (3.0% vs. 8.9%) and known-outcome analysis (0.6% vs. 5.6%). The known-outcome analysis demonstrated that uneven granulation had lower live birth rates than fine granulation (2.3% vs. 5.6%). Unexpectedly, the ooplasm granulation patterns were largely disassociated from embryo morphologic grades. We, for the first time, demonstrated that 4 distinct cytoplasmic granulation patterns in metaphase II oocytes had, largely independent of age and other variables, a predictive value for fertilization, pregnancy, and live birth outcomes in invitro fertilization cycles of poor-prognosis patients. These data suggest that upstream ooplasm granulation patterns deserve closer attention in terms of embryo selection.

Endometrial preparation for frozen-thawed embryo transfer cycles: a systematic review and network meta-analysis.

To compare the effects of different endometrial preparation protocols for frozen-thawed embryo transfer (FET) cycles and present treatment hierarchy. Systematic review with meta-analysis was performed by electronic searching of MEDLINE, the Cochrane Library, Embase, ClinicalTrials.gov and Google Scholar up to Dec 26, 2020. Randomised controlled trials (RCTs) or observational studies comparing 7 treatment options (natural cycle with or without human chorionic gonadotrophin trigger (mNC or tNC), artificial cycle with or without gonadotropin-releasing hormone agonist suppression (AC+GnRH or AC), aromatase inhibitor, clomiphene citrate, gonadotropin or follicle stimulating hormone) in FET cycles were included. Meta-analyses were performed within random effects models. Primary outcome was live birth presented as odds ratio (OR) with 95% confidence intervals (CIs). Twenty-six RCTs and 113 cohort studies were included in the meta-analyses. In a network meta-analysis, AC ranked last in effectiveness, with lower live birth rates when compared with other endometrial preparation protocols. In pairwise meta-analyses of observational studies, AC was associated with significant lower live birth rates compared with tNC (OR 0.81, 0.70 to 0.93) and mNC (OR 0.85, 0.77 to 0.93). Women who achieved pregnancy after AC were at an increased risk of pregnancy-induced hypertension (OR 1.82, 1.37 to 2.38), postpartum haemorrhage (OR 2.08, 1.61 to 2.78) and very preterm birth (OR 2.08, 1.45 to 2.94) compared with those after tNC. Natural cycle treatment has a higher chance of live birth and lower risks of PIH, PPH and VPTB than AC for endometrial preparation in women receiving FET cycles.

When using donor oocytes, does embryo stage matter? An analysis of blastocyst versus cleavage stage embryo transfers using a cryopreserved donor oocyte bank.

Oocyte donor in vitro fertilization (IVF) represents an ideal model to study the effects of embryo stage on reproductive success, as embryos come from young women with high-quality oocytes. Our study aimed to determine if embryo transfer stage affected outcomes in oocyte donor IVF, including the common scenario where only a limited number of quality embryos are available after culture. This retrospective cohort analyzed anonymous vitrified donor oocyte cycles at a single clinic between 2008 and 2015. Overall, 983 recipients underwent 1178 warming cycles resulting in fresh transfer of one-to-two embryos. Our primary outcome was live birth; secondary outcomes included multiple birth, birthweight, and gestational age. Log binomial regression with cluster-weighted generalized estimating equations were used to calculate adjusted risk ratios (aRR) accounting for recipient age, race, and transfer year. Among 132 cleavage and 1046 blastocyst transfer cycles, cleavage transfers were associated with lower probability of live birth (aRR 0.72, 95% CI 0.59-0.88). Subgroup analysis focused on cycles with a limited number of quality embryos 3 days post-fertilization (≤2), as clinically these women were most likely to be considered for cleavage transfers. Among these cycles (120 cleavage, 371 blastocyst), cleavage transfers were still associated with lower live birth rates compared to blastocyst (aRR 0.66, 95% CI 0.51-0.87) CONCLUSIONS: Even in a donor oocyte model with high-quality oocytes, there was a benefit to extended culture and blastocyst transfer, including when only one-to-two quality embryos were available after early culture. This is possibly owed to improved uterine synchronicity or decreased contractility.

The Endometrial Immune Profiling May Positively Affect the Management of Recurrent Pregnancy Loss.

IntroductionThe endometrial immune profiling is an innovative approach based on the analysis of the local immune reaction occurring in the endometrium at the time of the embryo implantation. By documenting the local immune activation during the period of uterine receptivity, we aim to detect and correct potential imbalances before and at the very beginning of placentation. The main objective of the study was to analyze in women with a history of repeated pregnancy loss (RPL) the association of personalized strategies based on immune dysregulations with live birth rates. The secondary objective was to highlight the main prognostic factors for live births.MethodsThis is an observational retrospective analysis of 104 patients with RPL, included between January 2012 and December 2019. Inclusion criteria included a spontaneous fertility with at least three miscarriages, an assessment including a three-dimension ultrasound scan, an endometrial biopsy for uterine immune profiling and a follow-up over at least 6 months with personalized care if indicated after the complete assessment. We defined as a success if the patients had a live birth after the suggested plan, as a failure if the patient either did not get pregnant or experienced a new miscarriage after the targeted therapies.ResultsUterine immune profiling was the only exploration to be significantly associated with a higher live birth rate (LBR) if a dysregulation was identified and treated accordingly (55% vs 45%, p=0.01). On the contrary, an absence of local dysregulation (resulting in an apparently balanced immune environment) was associated with a higher risk of a new miscarriage, suggesting that the cause inducing RPL still needed to be identified. Independently of age and AMH level, dysregulated immune profile is significatively associated with 3 times higher LBR than a non-deregulated profile (OR=3.4 CI 95%1.27-9.84) or five times in case of an overactive profile treated by immunotherapy (OR=5 CI 95% 1.65-16.5). The usage of ART was significantly associated with lower LBR regardless of the presence of a subfertility factor (p=0.012). Personalization of medical care using natural cycle or simple hormonal stimulation is associated with a significantly higher LBR than personalization including ART treatments regardless of maternal age and AMH level (OR= 2.9 CI 95% 1.03-8.88).ConclusionOur study suggests that some endometrial immune profiles with targeted management of RPL are associated with a higher rate of LBR. ART may be negatively associated with LBR.

Leave the past behind: women’s reproductive history shows no association with blastocysts’ euploidy and limited association with live birth rates after euploid embryo transfers

Is there an association between patients' reproductive history and the mean euploidy rates per biopsied blastocysts (m-ER) or the live birth rates (LBRs) per first single vitrified-warmed euploid blastocyst transfers? Patients' reproductive history (as annotated during counselling) showed no association with the m-ER, but a lower LBR was reported after euploid blastocyst transfer in women with a history of repeated implantation failure (RIF). Several studies have investigated the association between the m-ER and (i) patients' basal characteristics, (ii) ovarian stimulation strategy and dosage, (iii) culture media and conditions, and (iv) embryo morphology and day of full blastocyst development. Conversely, the expected m-ER due to women's reproductive history (previous live births (LBs), miscarriages, failed IVF cycles and transfers, and lack of euploid blastocysts among prior cohorts of biopsied embryos) still needs investigations. Yet, this information is critical to counsel new patients about a first cycle with preimplantation genetic testing for aneuploidy (PGT-A), but even more so after former adverse outcomes to prevent treatment drop-out. This observational study included all patients undergoing a comprehensive chromosome testing (CCT)-based PGT-A cycle with at least one biopsied blastocyst in the period April 2013-December 2019 at a private IVF clinic (n = 2676 patients undergoing 2676 treatments and producing and 8151 blastocysts). m-ER were investigated according to women's reproductive history of LBs: no/≥1, miscarriages: no/1/>1; failed IVF cycles: no/1/2/>2, and implantation failures after previous transfers: no/1/2/>2. Among the 2676 patients included in this study, 440 (16%) had already undergone PGT-A before the study period; the data from these patients were further clustered according to the presence or absence of euploid embryo(s) in their previous cohort of biopsied blastocysts. The clinical outcomes per first single vitrified-warmed euploid blastocyst transfers (n =1580) were investigated according to the number of patients' previous miscarriages and implantation failures. The procedures involved in this study included ICSI, blastocyst culture, trophectoderm biopsy without hatching in Day 3, CCT-based PGT-A without reporting segmental and/or putative mitotic (or mosaic) aneuploidies and single vitrified-warmed euploid blastocyst transfer. For statistical analysis, Mann-Whitney U or Kruskal-Wallis tests, as well as linear regressions and generalised linear models among ranges of maternal age at oocyte retrieval were performed to identify significant differences for continuous variables. Fisher's exact tests and multivariate logistic regression analyses were instead used for categorical variables. Maternal age at oocyte retrieval was the only variable significantly associated with the m-ER. We defined five clusters (<35 years: 66 ± 31%; 35-37 years: 58 ± 33%; 38-40 years: 43 ± 35%; 40-42 years: 28 ± 34%; and >42 years: 17 ± 31%) and all analyses were conducted among them. The m-ER did not show any association with the number of previous LBs, miscarriages, failed IVF cycles or implantation failures. Among patients who had already undergone PGT-A before the study period, the m-ER did not associate with the absence (or presence) of euploid blastocysts in their former cohort of biopsied embryos. Regarding clinical outcomes of the first single vitrified-warmed euploid blastocyst transfer, the implantation rate was 51%, the miscarriage rate was 14% and the LBR was 44%. This LBR was independent of the number of previous miscarriages, but showed a decreasing trend depending on the number of previous implantation failures, reaching statistical significance when comparing patients with >2 failures and patients with no prior failure (36% versus 47%, P < 0.01; multivariate-OR adjusted for embryo quality and day of full blastocyst development: 0.64, 95% CI 0.48-0.86, P < 0.01). No such differences were shown for previous miscarriage rates. The sample size for treatments following a former completed PGT-A cycle should be larger in future studies. The data should be confirmed from a multicentre perspective. The analysis should be performed also in non-PGT cycles and/or including patients who did not produce blastocysts, in order to investigate a putative association between women's reproductive history with outcomes other than euploidy and LBRs. These data are critical to counsel infertile couples before, during and after a PGT-A cycle, especially to prevent treatment discontinuation due to previous adverse reproductive events. Beyond the 'maternal age effect', the causes of idiopathic recurrent pregnancy loss (RPL) and RIF are likely to be endometrial receptivity and selectivity issues; transferring euploid blastocysts might reduce the risk of a further miscarriage, but more information beyond euploidy are required to improve the prognosis in case of RIF. No funding was received and there are no competing interests. N/A.

Serum progesterone levels greater than 32.5\xa0ng/ml on the day of embryo transfer are associated with lower live birth rate after artificial endometrial preparation: a prospective study

BackgroundPrevious observational studies have highlighted the negative effects of serum hormone levels at the minimum threshold during frozen embryo transfer (FET) cycles. However, still the questions regarding the maximum threshold level, and the highest allowed dosage of hormonal medications remain unresolved. The present study was conducted to determine whether there is any relationship between the serum progesterone and estradiol levels on the day of ET, and live birth rate (LBR) in patients receiving HRT in FET cycles.MethodsIn this prospective cohort study, eligible women who were undergoing their first or second FET cycles with the top graded blastocyst stage embryos were included. All patients received the same HRT regimen. FET was scheduled 5 days after administration of the first dosage of progesterone. On the morning of ET, 4–6 h after the last dose of progesterone supplementation, the serum progesterone (P4, ng/ml) and estradiol (E2, pg/ml) levels were measured.ResultsAmongst the 258 eligible women that were evaluated, the overall LBR was 34.1 % (88/258). The serum P4 and E2 values were divided into four quartiles. The means of women’s age and BMI were similar between the four quartiles groups. Regarding both P4 and E2 values, it was found that the LBR was significantly lower in the highest quartile group (Q4) compared with the others, (P = 0.002 and P = 0.042, respectively). The analysis of the multivariable logistic regression showed that the serum level of P4 on ET day, was the only significant predictive variable for LBR. The ROC curve revealed a significant predictive value of serum P4 levels on the day of ET for LBR, with an AUC = 0.61 (95 % CI: 0.54–0.68, P = 0.002). The optimum level of serum P4, with 70 % sensitivity and 50 %specificity for LBR, was 32.5 ng/ml.ConclusionsThe present study suggests that a serum P4 value at the maximum threshold on the day of FET is associated with reduced LBR following blastocyst transfer. Therefore, measuring and monitoring of P4 levels during FET cycles might be necessary. However, the results regarding the necessity for the screening of serum E2 levels before ET, are still controversial, and further prospective studies are required.

The effect of weight and body mass index on serum progesterone values and live birth rate in cryopreserved in vitro fertilization cycles

ObjectiveTo determine if weight or body mass index (BMI) affects the serum progesterone level at the time of the pregnancy test in cryopreserved blastocyst transfer cycles and to determine if those serum progesterone levels affect live births.DesignRetrospective cohort study.SettingUS academic medical center.Patient(s)Six hundred thirty-three patients undergoing their first cryopreserved embryo transfer cycle.Intervention(s)None.Main Outcome Measure(s)The primary outcome was the serum progesterone level on the day of the pregnancy test by patient weight and BMI. Our secondary analysis assessed the serum progesterone effect on live birth rate (LBR) in a clinic where progesterone supplementation was increased if the progesterone level was <15 ng/mL on the day of the pregnancy test.Results(s)There was a strong negative correlation between serum progesterone level and both BMI and weight, with BMI accounting for 27% and weight accounting for 29% of the variance in progesterone level. Serum progesterone level on the day of the pregnancy test was <15 ng/mL in 3% of women weighing <68 kg compared with 29% of women weighing ≥90.7 kg. Among women weighing ≥90.7 kg, live birth occurred in 47% whose serum progesterone level was <15 ng/mL on the day of the pregnancy test compared with 49% in those with serum progesterone level of 15–19 ng/mL and 44% in those with serum progesterone level of ≥20 ng/mL.Conclusion(s)Body weight was a significant factor in serum progesterone level at the time of the pregnancy test, with nearly 30% of patients weighing ≥90.7 kg having serum progesterone level of <15 ng/mL, a value associated with lower LBRs in prior studies. However, we found no effect of low progesterone levels on LBR after cryopreserved embryo transfer cycles in a clinic where progesterone dosing was increased if serum progesterone levels were <15 ng/mL.

Association between maternal prepregnancy body mass index and pregnancy outcomes following assisted reproductive technology: A systematic review and dose-response meta-analysis.

This systematic review investigated dose-response relationship between maternal prepregnancy body mass index (BMI) and pregnancy outcomes following assisted reproductive technology, including clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR). We searched four major databases and finally included 105 studies involving more than 271,632 pregnant women. We performed linear or nonlinear dose-response meta-analyses using random effects models. At per-woman level, pooling of unadjusted estimates shown an inverted J-shaped relationship between maternal BMI and CPR; pooling of adjusted estimates showed a linear association, suggesting statistical association between higher maternal BMI and lower CPR (adjusted OR [aOR] for 5-unit increase in BMI: 0.96, 95%CI: 0.94-0.98). At per-cycle level, linear dose-response relationship was found between maternal BMI and CPR (crude relative risk, RR, [cRR] for 5-unit increase in BMI 0.97, 0.96-0.98; aOR 0.96, 0.94-0.99). Linear dose-response relationship was established between maternal BMI and the outcomes of MR or LBR (higher BMI associated with higher MR [cRR 1.15, 1.08-1.22] and lower LBR [cRR 0.91, 0.88-0.94] at per-woman level). Sensitivity analyses showed no significant changes. In conclusion, there is dose-response relationship between maternal BMI and pregnancy outcomes following assisted reproductive technology. Higher BMI values may suggest suboptimal pregnancy outcomes.

Disposition of embryos from women who only produced morphologically poor embryos on day three

BackgroundThe presence of only morphologically poor embryos (MPEs) on day3 is common in autologous in vitro fertilization (IVF), particularly among p Tel: 886-7-7317123 Ext. 8916. Fax: 886-7-7322915.atients who have advanced maternal age or are poor responders. However, there are limited data regarding the disposition of embryos from patients who only produced MPEs on day3. The present study was designed to investigate the possible benefits of extended culturing MPEs. Try to detect whether the extended culture (day4 or day5 culture) can improve the live birth rate per cycle? MethodsThis retrospective, observational, single-center, cohort study examined 224 IVF/intracytoplasmic sperm injection (ICSI) cycles between January 2010 and June 2015, in which women only produced MPEs on day3. A total of 544 MPEs were analyzed. The defines a day3 embryo as an MPE if it fails to develop to eight cells, blastomeres of equal size, and less than 20% cytoplasmic fragments. Of the 224 cycles, 89 (39.7%) underwent fresh embryo transfer on day3, and 135 (60.3%) underwent extended culture. Of the 135 extended cultures, 54 cycles (40.0%) experienced day4, or day5 embryo transfer, 16 cycles (11.9%) had all embryos frozen, and 65 cycles (48.1%) had total embryo arrest. ResultsAnalysis of patient baseline demographic data, cycle characteristics, and cycle outcomes for day3 transfer group and extended culture group indicated that a higher body mass index in the day3 transfer group was the only significant difference (p = 0.006). Both fresh transfer groups had low live birth rates (LBRs) (4.5% vs. 7.4% p = 0.46). After extended culture, 65 cycles (48.1%) were cancelled because the embryos exhibited developmental arrest and 70 cycles (51.9%) grew to day4 or day5. Thirteen frozen embryo transfer (FET) cycles and 22 frozen blastocysts derived from MPEs were thawed. There were more high-quality embryos (p < 0.001), higher implantation rates (IRs) (p = 0.038), and higher LBRs (p = 0.042) for embryos that underwent FET cycles. MPES in extended culture transfer have favorable survival than MPES in day3 transfer. ConclusionThe extended culture of MPEs in fresh transfer cycles did not increase the LBR. However, younger females with the extended culture of MPEs followed by FET resulted in significantly higher LBRs and may be a feasible strategy to improve outcomes for patients with poor embryo quality. However, day3 embryo transfer may be a better choice if a fresh transfer is unrestricted and avoid the cycle cancellation. Extended culture may decrease to the transfer of developmental potential arrest embryos to patients.

Effect of Endometrial Thickness and duration of Estrogen Supplementation on In Vitro Fertilization-Intracytoplasmic Sperm Injection Outcomes in Fresh Ovum/Embryo Donation Cycles.

Background:There is no consensus regarding optimal endometrial thickness and duration of estrogen supplementation in embryo transfer cycles, at present.Aims:To observe the effect of endometrial thickness and/or duration of estrogen supplementation on in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes in fresh ovum/embryo donation cycles.Settings and Design:This was a retrospective observational study. The study was conducted from January 2015 to November 2017.Subjects and Methods:Nine hundred and fifty seven fresh blastocyst transfer cycles in the recipients of oocyte/embryo donation regardless of reproductive history and diagnosis conducted at Nova IVF Fertility, Ahmedabad, Gujarat, India. Of these, 315 women had single embryo transfer (SET), while 642 had double embryo transfer (DET). Only fresh blastocysts derived from oocytes of young donors (≤30 years) and transferred in a uniform hormone replacement therapy (HRT) cycle were included. The effect of endometrial thickness and duration of estrogen on live birth rate (LBR) and other IVF/ICSI outcomes were analyzed.Statistical Analysis:Univariate logistic regression.Results:A significant improvement in LBR was noted in the recipients with each millimeter increase in endometrial thickness starting from 6 mm after transfer of either single (odds ratio [OR] = 1.3, P = 0.003) or double (OR = 1.14, P = 0.0218) blastocysts. Lower LBR was observed in recipients having SET and who received estrogen supplementation of <10 days (OR = 0.72; P = 0.02). Implantation rate and clinical pregnancy rate also improved significantly with endometrial thickness, but there was no change in clinical abortion rate and ectopic pregnancy rate.Conclusions:After minimizing the possible oocyte factor by including only donor oocytes and that of COH using a uniform HRT protocol, LBR improved with each millimeter increase in endometrial thickness starting from 6 mm. Shorter duration of estrogen supplementation (<10 days) reduced the chances of live birth in recipients after transfer of a single blastocyst.

Novel insights on premature progesterone elevation: a mini-review

In vitro fertilization (IVF) success involves ovarian stimulation with conventional or mild stimulation protocols aimed to yield an adequate number of mature oocytes. These oocytes can be further fertilized and generate good quality embryos to be transferred, ideally in the same cycle. Since 2013, following the results of a meta-analysis including more than 60,000 IVF cycles, the negative effects of premature progesterone elevation on reproductive outcomes have been demonstrated. Nowadays, evidence is emerging on the limited regulation on serum progesterone values, demonstrating significantly lower live birth rates in patients with either low (<0.5ng/ml) late follicular phase progesterone or higher levels decreasing sharply. This review discusses and summarizes the different mechanisms of progesterone elevation and its impact on IVF treatments. Different approaches to diminish the impact of progesterone on fertility outcomes are also addressed.

Live birth and perinatal outcomes using cryopreserved oocytes: an analysis of the Human Fertilisation and Embryology Authority database from 2000 to 2016 using three clinical models.

Are live birth (LB) and perinatal outcomes affected by the use of frozen own versus frozen donor oocytes? Treatment cycles using frozen own oocytes have a lower LB rate but a lower risk of low birth weight (LBW) as compared with frozen donor oocytes. A rising trend of oocyte cryopreservation has been noted internationally in the creation of donor oocyte banks and in freezing own oocytes for later use in settings of fertility preservation and social egg freezing. Published literature on birth outcomes with frozen oocytes has primarily utilised data from donor oocyte banks due to the relative paucity of outcome data from cycles using frozen own oocytes. This was a retrospective cohort study utilising the anonymised database of the Human Fertilisation and Embryology Authority, which is the statutory regulator of fertility treatment in the UK. We analysed 988015 IVF cycles from the Human Fertilisation and Embryology Authority (HFEA) register from 2000 to 2016. Perinatal outcomes were assessed from singleton births only. Three clinical models were used to assess LB and perinatal outcomes: Model 1 compared frozen own oocytes (n = 632) with frozen donor oocytes (n = 922); Model 2 compared frozen donor oocytes (n = 922) with fresh donor oocytes (n = 24 706); Model 3 compared first cycle of fresh embryo transfer from frozen donor oocytes (n = 917) with first cycle of frozen embryo transfer created with own oocytes and no prior fresh transfer (n = 326). Preterm birth (PTB) was defined as LB before 37 weeks and LBW as birth weight <2500 g. Adjustment was performed for confounding variables such as maternal age, number of embryos transferred and decade of treatment. The LB rate (18.0% versus 30.7%; adjusted odds ratio (aOR) 0.61, 95% CI 0.43-0.85) and the incidence of LBW (5.3% versus 14.0%; aOR 0.29, 95% CI 0.13-0.90) was significantly lower with frozen own oocytes as compared with frozen donor oocytes with no significant difference in PTB (9.5% versus 15.7%; aOR 0.56, 95% CI 0.26-1.21). A lower LB rate was noted in frozen donor oocyte cycles (30.7% versus 34.7%; aOR 0.69, 95% CI 0.59-0.80) when compared with fresh donor oocyte cycles. First cycle frozen donor oocytes did not show any significant difference in LB rate (30.1% versus 19.3%; aOR 1.26, 95% CI 0.86-1.83) or PTB, but a higher incidence of LBW (17.7% versus 5.4%; aOR 3.77, 95% CI 1.51-9.43) as compared with first cycle frozen embryos using own oocytes. The indication for oocyte freezing, method of freezing used (whether slow-freezing or vitrification) and age at which eggs where frozen were unavailable. We report a subgroup analysis of women using their own frozen oocytes prior to 37 years. Cumulative LB rate could not be assessed due to the anonymous nature of the dataset. Women planning to freeze their own eggs for fertility preservation or social egg freezing need to be counselled that the results from frozen donor egg banks may not completely apply to them. However, they can be reassured that oocyte cryopreservation does not appear to have a deleterious effect on perinatal outcomes. No specific funding was sought for the study. The authors have no relevant conflicts of interest. N/A.

The risk of poor ovarian response during repeat IVF

Research questionWhat are the incidence and risk factors for poor ovarian response (POR) during repeat IVF? DesignA retrospective analysis of 1224 consecutive patients who underwent at least two IVF stimulations in a single centre over a 6-year period. Risk factors from the initial treatment were assessed for association with POR during repeat IVF using logistic regression analysis. A simple, practical predictive model was constructed and evaluated for accuracy and calibration, based on the factors that demonstrated significant association with subsequent POR. POR during repeat IVF was defined as ≤3 retrieved oocytes or cancellation before retrieval following recruitment of ≤3 mature follicles. ResultsThe risk of POR during repeat IVF was approximately 11.5%. A higher POR risk during repeat IVF is associated with a reduced oocyte yield during the initial treatment (≤3 oocytes: odds ratio [OR] 14, 95% confidence interval [CI] 6.42–30.24; 4–9 oocytes: OR 4.13, 95% CI 2.00–8.54; 10–15 oocytes: OR 1) and low ovarian reserve (anti-Müllerian hormone [AMH] <5.4 pmol/l: OR 3.54, 95% CI 2.24–5.59; AMH 5.4–25 pmol/l: OR 1). Women with low ovarian reserve who experience POR during the initial IVF have the highest risk of suffering POR again during repeat IVF (57% within 1 year). Other groups, such as women with unexpected POR or expected poor responders with suboptimal ovarian response during the initial IVF, are also at risk of exhibiting POR during a subsequent treatment (28% within 1 year). ConclusionsAs there is a clear association between POR and lower live birth rates, this practical model may help manage patients’ expectations during repeat IVF treatment.

Vitamin D supplementation prior to in vitro fertilisation in women with polycystic ovary syndrome: a protocol of a multicentre randomised, double-blind, placebo-controlled clinical trial

IntroductionPolycystic ovary syndrome (PCOS) is one of the leading causes of female infertility, affecting around 5% of women of childbearing age in China. Vitamin D insufficiency is common in women...

Status of racial disparities between black and white women undergoing assisted reproductive technology in the US

BackgroundNumerous studies have demonstrated substantial differences in assisted reproductive technology outcomes between black non-Hispanic and white non-Hispanic women. We sought to determine if disparities in assisted reproductive technology outcomes between cycles from black non-Hispanic and white non-Hispanic women have changed and to identify factors that may have influenced change and determine racial differences in cumulative live birth rates.MethodsThis is a retrospective cohort study of the SARTCORS database outcomes for 2014–2016 compared with those previously reported in 2004–2006 and 1999/2000. Patient demographics, etiology of infertility, and cycle outcomes were compared between black non-hispanic and white non-hispanic patients. Categorical values were compared using Chi-squared testing. Continuous variables were compared using t-test. Multiple logistic regression was used to assess confounders.ResultsWe analyzed 122,721 autologous, fresh, non-donor embryo cycles from 2014 to 2016 of which 13,717 cycles from black and 109,004 cycles from white women. The proportion of cycles from black women increased from 6.5 to 8.4%. Cycles from black women were almost 3 times more likely to have tubal and/or uterine factor and body mass index ≥30 kg/m2. Multivariate logistic regression demonstrated that black women had a lower live birth rate (OR 0.71;P < 0.001) and a lower cumulative live birth rate for their initial cycle (OR 0.64; P < 0.001) independent of age, parity, body mass index, etiology of infertility, ovarian reserve, cycle cancellation, past spontaneous abortions, use of intra-cytoplasmic sperm injection or number of embryos transferred. A lower proportion of cycles in black women were represented among non-mandated states (P < 0.001) and cycles in black women were associated with higher clinical live birth rates in mandated states (P = 0.006).ConclusionsDisparities in assisted reproductive technology outcomes in the US have persisted for black women over the last 15 years. Limited access to state mandated insurance may be contributory. Race has continued to be an independent prognostic factor for live birth and cumulative live birth rate from assisted reproductive technology in the US.