Live Birth Rate Research Articles

Application of the blastomere count variations "skip value" in the embryo AI assessment

Objective: To explore the correlation between blastomere count variations "skip value" which extracted from by time-lapse technology (TLT) combined with artificial intelligence (AI) and morphological features of in vitro fertilization (IVF) embryo, and to test its feasibility in clinical applications. Methods: This study was a diagnostic experiment (AI reassessment of embryo transferred patients), a total of 6 545 embryos from 1 226 patients who underwent IVF at the Women and Children's Hospital of Chongqing Medical University from December 2020 to December 2021 were retrospectively analyzed, of which 2 869 embryos were attempted to cultured to blastocyst stage by TLT. The embryo dynamic map (EDM) was drawn by Embryo Viewer, a TLT recording software, based on embryo developmental kinetics. The self-developed AI embryo evaluation software identified and recorded the number of cleavages in real time during embryonic development, and compared with the EDM, the correlation between the skip value formed by the change of cleavage sphere counts and the outcomes of the embryos was analyzed. The correlation among skip value, morphological score of embryo, implantation rate and live birth rate were performed by Spearman and step-up logistic regression. The receiver operating characteristic (ROC) curve was selected for reporting there relationship of skip value and morphology. Finally, predicting power of skip value for implantation and live birth rate were performed by ROC analysis. Results: The total skip values extracted from the blastomere count of embryos (72 hours post-fertilization) were negatively correlated with abnormal cleavage, blastocyst formation rate, day 3 (D3)-cell score, uneven size and fragmentation (the β values were -0.268, -0.116, -0.213, -0.159 and -0.222, respectively; all P<0.001); positively correlated with D3-cell number (β=0.034; P<0.001); negatively correlated with blastocyst formation rate and implantation rate (OR=0.97, 95%CI: 0.93-0.99, P=0.034; OR=0.96, 95%CI: 0.93-0.98, P=0.044). The power of predicting implantation were similar between the order selection of skip values and traditional morphology criteria [area under curve (AUC): 0.679 vs 0.620]. Live birth rate were negatively correlated with female age (OR=0.91, 95%CI: 0.88-0.93; P<0.001), D3 general score (OR=0.77, 95%CI: 0.59-0.99; P=0.045) and order selection of skip values (OR=0.98, 95%CI: 0.96-0.99; P=0.038), while positively correlated with retrieved oocyte number and endometrial thickness in embryo transferred (OR=1.08, 95%CI:1.05-1.11, P<0.001; OR=1.09, 95%CI:1.06-0.12, P<0.001, respectively) from multivariate regression analysis, and the power of predicting live birth was 0.666 for AUC. Conclusions: The skip value and its order form is a systematic quantification of embryo development, correlated with embryo developmental quality and clinical outcome. It could be an addition parameter for embryo culture and selection.

Predicting the pregnancy outcome: Uncovering the link between β-hCG, patient factors and live birth in IVF

ObjectiveThe objectives of the study were to correlate live birth rate with the initial level of β-hCG in all patients undergoing embryo transfer and develop a predictive model of live birth based on patients’ and assisted reproductive technology (ART) characteristics. Study designSingle-center retrospective cohort study, including a total of 7587 positive first serum β-hCG from women who performed fresh and frozen embryo transfer.Twenty-one variables related to patient characteristics and treatment modalities were analyzed by step-wise univariate analysis followed by multivariate analysis. The study included women between 18 and 45 years with a positive (>20 IU/L) serum β-hCG between January 2011 and December 2020 while it excluded cycles from donation of gametes, PGT and >3 embryos transferred simultaneously. Main results and the role of chance: Among the positive serum β-hCG measurements 5085 (67.0 %) resulted in live births. β-hCG was higher in the live birth group (691 IU/L) compared to the failed pregnancies group (304 IU/L) (p500 IU/mL provided a positive predictive value for live birth of 85.3 % (95 %CI 84.0–86.4).Failed pregnancies were more common among older maternal and paternal age. Previous abortions were more common in the failed pregnancies group (25.0 %) compared to the live birth group (19.4 %). The most common indication to treatment was male infertility, accounting for a larger portion in the live birth group (41.7 %). At multivariate analysis, the factors independently associated with live birth were: first serum β-hCG (OR 1.35, 95 %CI 1.32–1.37), maternal age (OR 0.93, 95 %CI 0.91–0.95), previous abortions (OR 0.77, 95 % CI 0.68–0.88). The number of embryos transferred showed a positive correlation below a maternal age of 39 (<35 years old OR 1.60, CI 95 % 1.32–1.94; <39 years old OR 1.27 CI 95 % 1.09–1.47). The prediction model incorporating these four variables resulted in a sensitivity and specificity with an area under the ROC curve of 0.798. Conclusion: The study confirms the importance of the first value of β-hCG and proposes a predictive model that takes into account maternal age, number of embryos transferred, and obstetric history, thereby aiding in couples’ counseling and ultimately improve patients’ care.

Assessing the developmental competence of oocytes matured following rescue in vitro maturation: a systematic review and meta-analysis.

To assess the developmental competence of oocytes matured following rescue in vitro maturation (IVM). PubMed, EmBASE, and SCOPUS were systematically searched for peer-reviewed original papers using relevant keywords and Medical Subject Heading terms. Study quality was assessed using the Newcastle-Ottawa Scale. Odds ratios with a 95% confidence interval were calculated by applying a random effects model. The primary outcomes were fertilization and blastulation rates. Secondary outcomes included abnormal fertilization, cleavage, euploidy, clinical pregnancy, and live-birth rates. Twenty-four studies were included in the meta-analysis. The oocytes matured following rescue IVM showed significantly reduced fertilization, cleavage, blastulation, and clinical pregnancy rates compared to sibling in vivo-matured oocytes. No significant differences were found for the euploidy and live-birth rates in euploid blastocyst transfer. In poor responders, a reduced fertilization rate was observed using in vitro-matured GV but not with in vitro-matured MI. A reduced cleavage rate in MI matured overnight compared to < 6 incubation hours was found. Our results showed compromised developmental competence in oocytes matured following rescue IVM. However, in poor responders, rescue IVM could maximize the efficiency of the treatment. Notably, our data suggests using in vitro MI matured within 6 incubation hours. CRD42023467232.

An expert opinion on rescuing atypically pronucleated human zygotes by molecular genetic fertilization checks in IVF.

IVF laboratories routinely adopt morphological pronuclear assessment at the zygote stage to identify abnormally fertilized embryos deemed unsuitable for clinical use. In essence, this is a pseudo-genetic test for ploidy motivated by the notion that biparental diploidy is required for normal human life and abnormal ploidy will lead to either failed implantation, miscarriage, or significant pregnancy complications, including molar pregnancy and chorionic carcinoma. Here, we review the literature associated with ploidy assessment of human embryos derived from zygotes displaying a pronuclear configuration other than the canonical two, and the related pregnancy outcome following transfer. We highlight that pronuclear assessment, although associated with aberrant ploidy outcomes, has a low specificity in the prediction of abnormal ploidy status in the developing embryo, while embryos deemed abnormally fertilized can yield healthy pregnancies. Therefore, this universal strategy of pronuclear assessment invariably leads to incorrect classification of over 50% of blastocysts derived from atypically pronucleated zygotes, and the systematic disposal of potentially viable embryos in IVF. To overcome this limitation of current practice, we discuss the new preimplantation genetic testing technologies that enable accurate identification of the ploidy status of preimplantation embryos and suggest a progress from morphology-based checks to molecular fertilization check as the new gold standard. This alternative molecular fertilization checking represents a possible non-incremental and controversy-free improvement to live birth rates in IVF as it adds to the pool of viable embryos available for transfer. This is especially important for the purposes of 'family building' or for poor-prognosis IVF patients where embryo numbers are often limited.

The effect of Chinese herbal medicine on male factor infertility: study protocol for a randomized controlled trial.

The global prevalence of infertility is 9%, with male factors potentially accounting for 40% to 60% of cases. Conventional treatments can be ineffective, invasive, costly, and linked to adverse effects and high risks. Previous studies have shown that, Chinese herbal medicine (CHM) can regulate the hypothalamus-pituitary-testis axis, improve sperm abnormalities and quality, mitigate oxidative stress, and decrease DNA fragmentation index (DFI). Yet, the evidence backing the use of Chinese herbal medicine (CHM) for treating male factor infertility lacks conviction due to study design limitations, and there remains a scarcity of studies on the live birth rate following CHM treatment for male factor infertility. Here, we describe the rationale and design of a randomized waitlist-controlled trial to evaluate the effect of CHM on the live birth rate among males with infertility. This study is a single-center, randomized, waitlist-controlled study. A total of 250 couples diagnosed with male factor infertility will be enrolled in this study and then randomly allocated into two groups in a 1:1 ratio. Male participants in CHM group (treatment group) will receive CHM once a day for 3 months. Male participants in the waitlist group (control group) will not receive any treatment for 3 months. After 3 months, participants in both groups need to be followed up for another 12 months. The primary outcome will be the live birth rate; secondary outcomes include semen quality parameters, DFI and pregnancy related outcomes. Safety will also be assessed. The purpose of this trial is to explore the effects and safety of CHM on the live birth rate among couples dealing with male factor infertility. The outcome of this trial may provide a viable treatment option for male factor infertility. Chinese Clinical Trial Registry: ChiCTR2200064416. Registered on 7 October 2022, https://www.chictr.org.cn.

Clinical effectiveness and safety of time-lapse imaging systems for embryo incubation and selection in in-vitro fertilisation treatment (TILT): a multicentre, three-parallel-group, double-blind, randomised controlled trial

Time-lapse imaging systems for embryo incubation and selection might improve outcomes of in-vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI) treatment due to undisturbed embryo culture conditions, improved embryo selection, or both. However, the benefit remains uncertain. We aimed to evaluate the effectiveness of time-lapse imaging systems providing undisturbed culture and embryo selection, and time-lapse imaging systems providing only undisturbed culture, and compared each with standard care without time-lapse imaging. We conducted a multicentre, three-parallel-group, double-blind, randomised controlled trial in participants undergoing IVF or ICSI at seven IVF centres in the UK and Hong Kong. Embryologists randomly assigned participants using a web-based system, stratified by clinic in a 1:1:1 ratio to the time-lapse imaging system for undisturbed culture and embryo selection (time-lapse imaging group), time-lapse imaging system for undisturbed culture alone (undisturbed culture group), and standard care without time-lapse imaging (control group). Women were required to be aged 18-42 years and men (ie, their partners) 18 years or older. Couples had to be receiving their first, second, or third IVF or ICSI treatment and could not participate if using donor gametes. Participants and trial staff were masked to group assignment, embryologists were not. The primary outcome was live birth. We performed analyses using the intention-to-treat principle and reported the main analysis in participants with primary outcome data available (full analysis set). The trial is registered on the International Trials Registry (ISRCTN17792989) and is now closed. 1575 participants were randomly assigned to treatment groups (525 participants per group) between June 21, 2018, and Sept 30, 2022. The live birth rates were 33·7% (175/520) in the time-lapse imaging group, 36·6% (189/516) in the undisturbed culture group, and 33·0% (172/522) in the standard care group. The adjusted odds ratio was 1·04 (97·5% CI 0·73 to 1·47) for time-lapse imaging arm versus control and 1·20 (0·85 to 1·70) for undisturbed culture versus control. The risk reduction for the absolute difference was 0·7 percentage points (97·5% CI -5·85 to 7·25) between the time-lapse imaging and standard care groups and 3·6 percentage points (-3·02 to 10·22) between the undisturbed culture and standard care groups. 79 serious adverse events unrelated to the trial were reported (n=28 in time-lapse imaging, n=27 in undisturbed culture, and n=24 in standard care). In women undergoing IVF or ICSI treatment, the use of time-lapse imaging systems for embryo culture and selection does not significantly increase the odds of live birth compared with standard care without time-lapse imaging. Barts Charity, Pharmasure Pharmaceuticals, Hong Kong OG Trust Fund, Hong Kong Health and Medical Research Fund, Hong Kong Matching Fund.

Effect of different treatment protocols on in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) outcomes in adenomyosis women: a systematic review and meta-analysis

ObjectivesPregnancy outcomes of different ovarian stimulation protocols for in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) in patients with adenomyosis are not explicit. This meta-analysis aimed to systematically evaluate the effects of...

Association between subchorionic hematoma in the first trimester and outcomes of singleton pregnancies achieved through assisted reproductive technology: a systematic review and meta-analysis.

To evaluate the association between first trimester (≤ 12 weeks gestation) subchorionic hemorrhage (SCH), and maternal and neonatal outcomes in women who conceived with the help of assisted reproductive technique (ART). PubMed, Embase, Web of Science, and Scopus databases were searched for observational studies that specifically focused on women who achieved pregnancy via ART and investigated the relationship between early pregnancy (within 12 weeks of gestation) SCH and maternal and neonatal outcomes. Only studies with singleton pregnancies and reporting data on the comparator group (women without SCH) were included. Primary outcomes of interest included incidences of early (within 20 weeks of gestation) pregnancy loss, preterm delivery, caesarean section, and live birth rates. Pooled effect sizes were reported as odds ratio (OR) with 95% confidence intervals (CI). Nine studies were included. All studies had a cohort design. In all studies, the primary assisted reproduction technique used was in-vitro fertilization (IVF). Compared to pregnancies without SCH, women with diagnosed early pregnancy SCH have a similar risk of preterm birth (< 37 weeks) (OR 1.01, 95% CI 0.83, 1.22), low birth weight (< 2500 g) (OR 1.01, 95% CI 0.59, 1.73) and fetal growth restriction (OR 1.57, 95% CI 0.62, 4.02). The gestational age (in weeks) (weighted mean difference (WMD) - 0.06, 95% CI - 0.18, 0.06) and the birth weight (in grams) (WMD - 16.5, 95% CI - 62.9, 29.8) were also similar in the two groups. The odds of early pregnancy loss (OR 1.39, 95% CI 0.97, 2.01), live birth (OR 0.77, 95% CI 0.55, 1.08) and caesarean delivery (OR 0.97, 95% CI 0.81, 1.16) were statistically similar in both groups. The risk of maternal adverse outcomes such as gestational diabetes (OR 0.98, 95% CI 0.74, 1.29), hypertensive disorder (OR 0.95, 95% CI 0.63, 1.43), premature rupture of membranes (PROM) (OR 1.36, 95% CI 0.90, 2.05) and placental abruption (OR 2.44, 95% CI 0.57, 10.5) was also similar in both the groups. There was no evidence of publication bias. The findings suggest that SCH may not significantly increase the risk of adverse maternal and perinatal outcomes in pregnancies conceived through ART, particularly IVF. PROSPERO registration number CRD42024533996.

Does adding coenzyme Q10 to dehydroepiandrosterone sulphate positively impact fertility outcomes in young, poor responder infertile women undergoing antagonist protocol for IVF/ICSI cycles?

Background. One of the biggest issues in reproductive medicine is treating women with low ovarian reserves or a poor ovarian response (POR) to stimulation. Oxidative stress was suggested as one of the major contributors to POR. However, the pathophysiology remains unknown. Focusing on certain subpopulations within the diverse group of poor responders may help determine the best therapy for these patients. Objective. To investigate the effect of adding coenzyme A Q10 to dehydroepiandrosterone (DHEA) in young, poor responder infertile females undergoing in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Methods. One hundred and sixty-eight females with poor ovarian response (Poseidon Group 3) from multiple centres were randomly divided into two groups. The first group received DHEA orally along with coenzyme 10, while the second group received only DHEA. Both groups underwent controlled ovarian stimulation. Results. There was a significant improvement in the quality of oocytes and the number and quality of embryos transferred in the coenzyme A Q10 group. However, no significant differences were observed in other parameters between the groups. Conclusion. In young, poor-responder women with decreased ovarian reserve, pretreatment with CoQ10 enhances oocyte and embryo quality and boosts ovarian response to stimulation. An improvement in clinical pregnancy and live birth rates may be possible.

Inositols and female reproduction disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-Women's Endocrinology.

To provide the latest scientific knowledge on the efficacy of inositols for improving reproductive disorders in women with and without polycystic ovary syndrome (PCOS) and to reach a consensus on their potential use through a Delphi-like process. A panel of 17 endocrinologists and 1 gynecologist discussed 4 key domains: menses irregularity and anovulation, fertility, pregnancy outcomes, and neonatal outcomes. A total of eight consensus statements were drafted. Myo-inositol (Myo) supplementation can be used to improve menses irregularities and anovulation in PCOS. Myo supplementation can be used in subfertile women with or without PCOS to reduce the dose of r-FSH for ovarian stimulation during IVF, but it should not be used to increase the clinical pregnancy rate or live birth rate. Myo supplementation can be used in the primary prevention of gestational diabetes mellitus (GDM), but should not be used to improve pregnancy outcomes in women with GDM. Myo can be preconceptionally added to folic acid in women with a previous neural tube defects (NTD)-complicated pregnancy to reduce the risk of NTDs in newborns. Myo can be used during pregnancy to reduce the risk of macrosomia and neonatal hypoglycemia in mothers at risk of GDM. This consensus statement provides recommendations aimed at guiding healthcare practitioners in the use of inositols for the treatment or prevention of female reproductive disorders. More evidence-based data are needed to definitively establish the usefulness of Myo, the appropriate dosage, and to support the use of D-chiro-inositol (DCI) or a definitive Myo/DCI ratio.

Multiple collapses of blastocysts after full blastocyst formation is an independent risk factor for aneuploidy — a study based on AI and manual validation

BackgroundThe occurrence of blastocyst collapse may become an indicator of preimplantation embryo quality assessment. It has been reported that collapsing blastocysts can lead to higher rates of aneuploidy and poorer clinical outcomes, but more large-scale studies are needed to explore this relationship. This study explored the characteristics of blastocyst collapse identified and quantified by artificial intelligence and explored the associations between blastocyst collapse and embryo ploidy, morphological quality, and clinical outcomes.MethodsThis observational study included data from 3288 biopsied blastocysts in 1071 time-lapse preimplantation genetic testing cycles performed between January 2019 and February 2023 at a single academic fertility center. All transferred blastocysts are euploid blastocysts. The artificial intelligence recognized blastocyst collapse in time-lapse microscopy videos and then registered the collapsing times, and the start time, the recovery duration, the shrinkage percentage of each collapse. The effects of blastocyst collapse and embryo ploidy, pregnancy, live birth, miscarriage, and embryo quality were studied using available data from 1196 euploid embryos and 1300 aneuploid embryos.Results5.6% of blastocysts collapsed at least once only before the full blastocyst formation (tB), 19.4% collapsed at least once only after tB, and 3.1% collapsed both before and after tB. Multiple collapses of blastocysts after tB (times ≥ 2) are associated with higher aneuploid rates (54.6%, P > 0.05; 70.5%, P < 0.001; 72.5%, P = 0.004; and 71.4%, P = 0.049 in blastocysts collapsed 1, 2, 3 or ≥ 4 times), which remained significant after adjustment for confounders (OR = 2.597, 95% CI 1.464–4.607, P = 0.001). Analysis of the aneuploid embryos showed a higher ratio of collapses and multiple collapses after tB in monosomies and embryos with subchromosomal deletion of segmental nature (P < 0.001). Blastocyst collapse was associated with delayed embryonic development and declined blastocyst quality. There is no significant difference in pregnancy and live birth rates between collapsing and non-collapsing blastocysts.ConclusionsBlastocyst collapse is common during blastocyst development. This study underlined that multiple blastocyst collapses after tB may be an independent risk factor for aneuploidy which should be taken into account by clinicians and embryologists when selecting blastocysts for transfer.

Optimizing single blastocyst selection: the role of day 3 embryo morphology in vitrified-warmed blastocyst transfer cycles

Can day 3 embryo morphology serve as an independent criterion for optimal single blastocyst selection? This retrospective, single-centre cohort study included 1517 single vitrified-warmed blastocyst transfer (SVBT) cycles conducted between October 2019 and July 2022. The live birth rate (LBR) and other clinical outcomes of SVBT cycles were evaluated, considering both good-quality and non-good-quality day 3 embryos. The associations of day 3 morphological characteristics, encompassing number of blastomeres and embryo grade, were assessed. Multivariable analyses were undertaken using multiple models adjusted for day of blastocyst development and blastocyst grade. Blastocysts from good-quality day 3 embryos had significantly higher LBR compared with those from non-good-quality embryos for both day 5 (51.5% versus 42.9%; P = 0.013) and day 6 (25.1% versus 17.6%; P = 0.018) blastocysts. LBR did not differ significantly with number of blastomeres on day 3, regardless of day of blastocyst development (day 5/6) or blastocyst grade. LBR varied significantly by day 3 embryo grade for both day 5 (48.0%, 51.5%, 46.6% and 32.7% for grades I, II, III and IV-V; P = 0.005) and day 6 (41.5%, 23.6%, 15.9% and 16.1% for grades I, II, III and IV-V; P = 0.001) blastocysts. Multivariable logistic regression revealed that non-good-quality embryos and lower morphological grade (IV-V) on day 3 were significantly and negatively correlated with LBR, while the number of blastomeres on day 3 was not an independent factor. When selecting blastocysts of equal quality for SVBT cycles, those with higher day 3 morphological scores are preferred. Day 3 morphological evaluation is a valuable supplement to conventional selection methods.

Hysteroscopic Endometrial Fundal Incision versus Hysteroscopy Only in Oocyte Recipients: A Randomized Controlled Trial Assessing The Reproductive Outcomes.

Endometrial scratching (ES) remains controversial regarding its potential effectiveness in improving pregnancy rates. The objective of the present study was to assess the impact of endometrial fundal incision (EFI) during hysteroscopy on reproductive outcomes in a population of oocyte recipients. A randomized controlled trial was conducted between 2020 and 2023 at the Third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki and "Assisting Nature Centre of Reproduction and Genetics". The study population consisted of women who underwent hysteroscopy randomly assigned in a 1:1 ratio to either EFI (one to three months before embryotransfer with donor oocytes) or no intervention throughout office hysteroscopy. Clinical pregnancy and live birth rates were the primary outcomes. After the exclusion of patients with intraoperative diagnosed endometrial pathology, a total of 124 women underwent randomization. The pregnancy test was positive in 79% (n=49/62) of the women in the EFI compared to 59.7% (n=37/62) in the hysteroscopy-only group (P=0.019), while the live birth rates did not differ between the two groups (58.1%, n=36/62 vs. 51.6%, n=32/62, P=0.470). EFI during hysteroscopy seems to improve pregnancy rates in oocyte recipients without intrauterine pathology, while live birth rates are not affected by the EFI. These results should be interpreted with caution before the implementation of EFI in the routine in vitro fertilization (IVF) practice (registration number: NCT04580056).

The Efficiency of Introducing Intrauterine Infusion of Autologous Platelet-Rich Plasma versus Granulocyte Colony-Stimulating Factor in Repeated Implantation Failure Patients: An Unblinded Randomised Clinical Trial.

Repeated implantation failure (RIF) refers to the condition where high quality embryos are unable to successfully implant after multiple cycles of in vitro fertilization (IVF) treatment. The aim of this study is to investigate the impact of intrauterine granulocyte colony-stimulating factor (G-CSF) and platelet-rich plasma (PRP) on pregnancy rate in patients with RIF. The present randomised clinical trial study was conducted at the IVF Centre of Mehr Medical Institute in Rasht, Iran, from 2020 to 2022. The research consisted of 200 individuals who had experienced multiple failed cycles. These patients were randomised into two groups: intrauterine infusion of 1 ml of G-CSF and intrauterine infusion of 1 ml autologous PRP at least 48 hours before embryo transfer (ET). The groups were compared in terms of implantation rate, and chemical, clinical, and ongoing pregnancy. The implantation rate was significantly higher in patients who received PRP (P=0.016). Chemical pregnancy in the PRP group was significantly higher than G-CSF group (P=0.003). Both clinical pregnancy and ongoing pregnancy rates were significantly higher in the PRP group (P=0.001) compared to the G-CSF group (P=0.02). The utilisation of PRP via intrauterine infusion is considerably more successful than G-CSF in enhancing pregnancy and live birth rates among patients with RIF.

Live Birth after Cleavage-Stage versus Blastocyst-Stage Embryo Transfer in Assisted Reproductive Technology: A Randomised Controlled Study.

Blastocyst stage transfer appears to improve pregnancy outcomes. The aim of this study is to evaluate the pregnancy results between fresh cycle blastocyst stage embryo transfer and cleavage stage embryo transfer in patients who undergo intracytoplasmic sperm injection (ICSI). This randomised clinical trial study was conducted at the Infertility Research Centre of Milad Hospital in Mashhad, Iran from 2018 to 2020 on 240 infertile women who presented for their first ICSI procedure. These patients were assigned to receive either cleavage embryo transfer (n=112) or blastocyst stage transfer (n=107). Pregnancy outcomes were measured in both groups. There were no differences regarding age, body mass index (BMI), serum follicle-stimulating hormone (FSH), duration of infertility, and aetiology of infertility between the groups (P>0.05). There were more follicles, total oocytes, and metaphase II (M2) oocytes in the blastocyst stage group. Considerably more cleavage stage embryos were transferred compared to the number of transferred blastocysts (P=0.001). The blastocyst group had more vitrified embryos than the cleavage group (P=0.000). The rates of implantation (P=0.332), chemical pregnancy (P=0.165), clinical pregnancy (P=0.694), and live births (P=0.727) were higher in the blastocyst group, but they were not significantly different. The rate of abortion was also not significantly higher in the blastocyst group (P=0.296). Blastocysts transferred in the fresh cycle of an ICSI procedure may be more advantageous compared to cleavage stage embryo transfer (registration number: IRCT20181030041503N1).

Effect of time since vasectomy on live birth rate of TESE‒ICSI egg donation cycles and male-related prognostic factors.

Vasectomy is a widely used method of contraception. However, some men may have the desire to become biological fathers again after a period. To explore the effect of time since vasectomy and different male comorbidities on live birth rates from intracytoplasmic sperm injection cycles using donated oocytes by using testicular spermatozoa obtained by testicular sperm extraction. This was a retrospective study of 123 couples who underwent a testicular sperm extraction‒intracytoplasmic sperm injection cycle after vasectomy using donated oocytes. Subjects were divided into groups according to time since vasectomy and the male risk factor evaluated. The main outcomes measured were live birth rate per embryo transfer, per oocyte donation cycle, and per couple. We assessed the cumulative live birth rate according to the time since vasectomy and considered male comorbidities: body mass index, hypertension, diabetes mellitus, dyslipidemia, and smoking. The overall live birth rate per couple was 59.3% (50.6-68.0). Considering the number of embryo transfer and oocyte donation cycle, the live birth rates were 34.1% (27.8-40.4) and 44.5% (36.9-52.1), respectively. The live birth rate according to time since vasectomy was not statistically different between groups. Consequently, the cumulative live birth rate was similar between the different interval times when considering one to eight embryo transfers (p=0.74). No statistical differences in live birth rate and cumulative live birth rate were found between groups clustered according to male body mass index, smoking, hypertension, and dyslipidemia. However, diabetic male patients had a significantly lower rate of live birth rate per couple (22.2% [4.94-49.4]) than non-diabetic patients did (62.7% [53.7-71.8]) (p=0.03), but not in their cumulative live birth rate. The time since vasectomy seems to have no detrimental effects on the live birth rate and cumulative live birth rate in testicular sperm extraction‒intracytoplasmic sperm injection cycles with donated oocytes. Male diabetes negatively affects the overall live birth rate per couple, but not the cumulative live birth rate. These results could be useful for multidisciplinary patient-tailored counseling, regarding the chance of having a pregnancy and facilitating the decision-making process of the fertility specialists.

Improvement of early miscarriage rates in women with adenomyosis via oxytocin receptor antagonist during frozen embryo transfer-a propensity score-matched study

BackgroundDysfunctional uterine peristalsis seems to play a pivotal role in hindering embryo implantation among women diagnosed with adenomyosis. This research aims to investigate whether administering an oxytocin receptor antagonist during a frozen embryo transfer (FET) cycle using a hormone replacement therapy (HRT) protocol can enhance in vitro fertilization (IVF) outcomes for infertile women affected by adenomyosis.MethodsBetween January 2018 and June 2022, our reproductive center conducted IVF-FET HRT cycles for infertile women diagnosed with adenomyosis. Propensity score matching was employed to select matched subjects between the two groups in a 1:1 ratio. Following this, 168 women received an oxytocin receptor antagonist during FET, constituting the study group, while the matched 168 women underwent FET without this antagonist, forming the control group. We conducted comparative analyses of baseline and cycle characteristics between the two groups, along with additional subgroup analyses.ResultsThe study group exhibited notably lower rates of early miscarriage compared to the control group, although there were no significant differences in clinical pregnancy rates, ongoing pregnancy rates, and live birth rates between the two groups. Multivariate analysis revealed a negative correlation between the use of oxytocin receptor antagonists and early miscarriage rates in women with adenomyosis. Subgroup analyses, categorized by age, infertility types, and embryo transfer day, showed a substantial decrease in early miscarriage rates within specific subgroups: women aged ≥ 37 years, those with secondary infertility, and individuals undergoing day 3 embryo transfers in the study group compared to the control group. Furthermore, subgroup analysis based on adenomyosis types indicated significantly higher clinical pregnancy rates, ongoing pregnancy rates and live birth rates in the study group compared to the control group among women with diffuse adenomyosis.ConclusionsAdministering an oxytocin receptor antagonist during FET may reduce the early miscarriage rates in women with adenomyosis.

Assessing vaginal microbiome through Vaginal Microecology Evaluation System as a predictor for in vitro fertilization outcomes: a retrospective study.

This study aims to evaluate the effectiveness of the Vaginal Microecology Evaluation System (VMES) in assessing the dynamics of the vaginal microbiome (VM) throughout the process of in vitro fertilization and embryo transfer (IVF-ET). Furthermore, it seeks to explore the potential correlation between distinct types of VM ecology and the success rate of IVF-ET. This study employed VMES to ascertain the composition of the VM. Data were collected from infertile women who underwent their initial IVF-ET treatment for tubal factor between January 2018 and December 2021. A retrospective analysis of pregnancy outcomes resulting from their fresh embryo transfer was conducted to determine the predictive significance of the vaginal microenvironment. We demonstrate that VMES is able to predict IVF-ET outcomes in patients diagnosed with Bacterial Vaginosis (BV). Notably, a discernible shift in the VM was observed in a decent subset of patients following Controlled Ovarian Stimulation (COS), though this phenomenon was not universal across all participants. Specifically, there was a noteworthy increase in the proportion of patients exhibiting BV and uncharacterized dysbiosis subsequent to COS. Furthermore, our investigation revealed a significant correlation between VM and both the live birth rate and early miscarriage rate. Employing a multivariable logistic regression model, we identified that VM status pre-COS, VM status post-COS, patient age, and the number of embryos transferred emerged as independent predictors of the live birth rate. Our study suggests that, during IVF-ET treatment, the VMES can effectively detect changes in the VM, which are strongly correlated with the pregnancy outcome of IVF-ET procedures.

Meta-analysis of intrauterine hCG perfusion efficacy in recurrent implantation failure as defined by ESHRE guidelines

PurposeThis study evaluates the efficacy of intrauterine hCG perfusion for RIF, as defined by ESHRE 2023 guidelines, highlighting hCG as a cost-effective alternative to other immunotherapies, especially suitable for less developed regions. It aims to clarify treatment guidance amidst previous inconsistencies.MethodsThis meta-analysis, registered with PROSPERO (CRD42024443241) and adhering to PRISMA guidelines, assessed the efficacy and safety of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in RIF. Comprehensive literature searches were conducted through December 2023 in major databases including PubMed, Web of Science, Embase, the Cochrane Library, and key Chinese databases, without language restrictions. Inclusion and exclusion criteria were strictly aligned with the 2023 ESHRE recommendations, with exclusions for studies lacking robust control, clear outcomes, or adequate data integrity. The risk of bias was evaluated using the Newcastle-Ottawa Scale, ROBINS-I, and RoB2 tools. Data analysis was performed in R using the ‘meta’ package, employing both fixed and random effect models to account for study variability. Subgroup analyses by dosage, volume, hCG concentration, timing of administration, and type of embryo transfer were conducted to deepen insights, enhancing the reliability and depth of the meta-analysis in elucidating the role of hCG perfusion in RIF treatments.ResultsData from 13 studies, comprising six retrospective and six prospective studies from single centers, along with one multi-center RCT, totaling 2,157 participants, were synthesized to evaluate the effectiveness of intrauterine hCG perfusion in enhancing implantation and pregnancy outcomes in patients with RIF. Significant improvements were observed in clinical pregnancy and embryo implantation rates across various dosages, timing of administration, and embryo developmental stages, without impacting miscarriage rates. Notably, the most significant efficacy within subgroups occurred with a 500 IU dosage and perfusion parameters of ≤ 500µL volume and ≥ 2 IU/µL concentration. Additionally, a limited number of studies showed no significant increases in ectopic pregnancy or multiple pregnancy rates, and a modest improvement in live birth rates, although the small number of these studies precludes definitive conclusions.ConclusionsThe analysis suggests that intrauterine hCG perfusion probably enhances embryo implantation, clinical pregnancy, and live birth rates slightly in RIF patients. Benefits are indicated with a dosage of 500 IU and a maximum volume of 500µL at concentrations of at least 2 IU/µL. However, substantial heterogeneity from varying study types and the limited number of studies necessitate cautious interpretation. These findings underscore the need for more rigorously designed RCTs to definitively assess the efficacy and safety.

Association between pre-gravid body mass index and clinical outcomes in in vitro fertilization: a multicentered retrospective cohort study

BackgroundWith the increasing incidence of obesity and the childbearing-age delay among women, a debate over obesity’s impacts on pregnancy and neonatal outcomes becomes hot. The potential negative effects of obesity and aging on fertility lead to an idea, whether an obese female pursuing IVF treatment can benefit from an ideal BMI achieved over a long-time weight loss process at the cost of aging? We aimed to assess the association between body mass index (BMI) and clinical or neonatal outcomes in patients undergoing in vitro fertilization (IVF) treatment, for answering whether it is necessary to lose weight first for obese patients, particularly those at advanced age.MethodsA retrospective cohort study was performed using multicentered data from China. The women were stratified into 5 groups in terms of pre-gravid BMI (kg/m2) with the WHO obesity standard (group 1: BMI < 18.5; group 2: 18.5 ≤ BMI < 23.0; group 3: 23.0 ≤ BMI < 25.0; group 4: 25.0 ≤ BMI < 30.0; group 5: BMI ≥ 30.0). The primary outcome was cumulative live birth rate (CLBR), and other clinical and neonatal outcomes were weighed as secondary outcomes. Multivariate logistic regression analyses were carried to evaluate the association between BMI and the CLBR, or between BMI and some neonatal outcomes. Furthermore, we implemented a machine-learning algorithm to predict the CLBR based on age and BMI.ResultsA total of 115,287 women who underwent first IVF cycles with autologous oocytes from January 2013 to December 2017 were included in our study. The difference in the CLBR among the five groups was statistically significant (P < 0.001). The multivariate logistic regression analysis showed that BMI had no significant impact on the CLBR, while women’s age associated with the CLBR negatively. Further, the calculation of the CLBR in different age stratifications among the five groups revealed that the CLBR lowered with age increasing, quantitatively, it decreased by approximately 2% for each one-year increment after 35 years old, while little difference observed in the CLBR corresponding to the five groups at the same age stratification. The machine-learning algorithm derived model showed that BMI’s effect on the CLBR in each age stratification was negligible, but age’s impact on the CLBR was overwhelming. The multivariate logistic regression analysis showed that BMI did not affect preterm birth, low birth weight infant, small for gestational age (SGA) and large for gestational age (LGA), while BMI was an independent risk factor for fetal macrosomia, which was positively associated with BMI.ConclusionsMaternal pre-gravid BMI had no association with the CLBR and neonatal outcomes, except for fetal macrosomia. While the CLBR was lowered with age increasing. For the IVF-pursuing women with obesity plus advanced age, rather than losing weight first, the sooner the treatment starts, the better. A multicentered prospective study with a large size of samples is needed to confirm this conclusion in the future.