Good Quality Embryos Research Articles

Does current ovarian endometrioma increase the time for DOR patients to reach live birth in IVF?

BackgroundThe contents of ovarian endometrioma (OMA) such as inflammatory mediators, reactive oxygen species, and iron may disrupt normal folliculogenesis and result in subsequent oocyte apoptosis. Therefore, women with OMA have a potential risk of diminished ovarian reserve (DOR). The purpose of this study is to compare the in vitro fertilization (IVF) outcomes and efficiency between DOR patients with and without current OMA.MethodsThis retrospective case-control study included a total of 493 women with DOR (serum anti-Müllerian hormone level < 1.1 ng/mL). Ninety patients with OMA (Group A) underwent 191 IVF cycles and 403 patients without ovarian OMA (Group B) underwent 888 IVF cycles in our center between January 2014 and December 2018. Basal characteristics and IVF outcomes were compared between Group A and Group B. Time to achieve live birth were compared between patients with live birth in two groups (Group A1, 31 patients; Group B1, 132 patients).ResultsClinical and demographic characteristics of patients were similar respectively between groups (A vs. B, A1 vs. B1). There were no statistically significant differences in implantation rate, live birth rate per OPU and per ET cycle and the cumulative live birth rate per patient and per patient with good-quality embryos between Group A and Group B (P > 0.05). Total time to achieve live birth has no statistically significant difference between Group A1 and Group B1 (P > 0.05).ConclusionFor DOR women, presence of endometrioma did not affect the IVF outcomes. Even the time to get live birth was not prolonged by current OMA.

ICSI outcomes for infertile men with severe or complete asthenozoospermia

BackgroundSevere or complete asthenozoospermia is a rare entity that can lead to male infertility. In this study, we explored whether different extents of severe or complete asthenozoospermia could affect intracytoplasmic sperm injection (ICSI) outcomes and compared the ICSI outcomes using testicular spermatozoa with those using ejaculated spermatozoa in couples with complete asthenozoospermia.ResultsNinety-seven couples with severe or complete asthenozoospermia who underwent ICSI between January 2014 and December 2018 were included. According to the sperm category used in ICSI, patients were categorized into four groups: ejaculated progressive motile sperm group (Ep-group), ejaculated non-progressive motile sperm group (En-group), ejaculated immotile sperm group (Ei-group), and testicular sperm group (TESE-group). We compared the baseline characteristics, hormone profile, semen parameters, normal fertilization, good-quality embryos on day 3, transferred embryos, and ICSI outcomes in the four groups. The clinical pregnancy rate was significantly increased in the Ep-group (65.4%, P = 0.019) and TESE-group (63.6%, P = 0.035) compared with that in the Ei-group (23.1%). The ongoing pregnancy rate in the Ei-group was significantly lower than that in the Ep-group (23.1% vs. 61.5%, P = 0.041). Moreover, the biochemical pregnancy rate, ongoing pregnancy rate, and live birth rate were much lower in the Ei-group than in the TESE-group (30.8% vs. 63.6%, 23.1% vs. 40.4% and 23.1% vs. 40.4%, respectively).ConclusionsIn couples with complete asthenozoospermia, testicular spermatozoa should be preferred to ejaculated spermatozoa for obtaining a better ICSI outcome. With the appropriate selection of testicular spermatozoa, the extent of severe or complete asthenozoospermia may not affect the ICSI outcomes. Future studies with a larger sample size are warranted to validate these findings.

Sperm Activation with Pentoxifylline Is Beneficial For Non-Obstructive Azoospermia Patients Using Testicular Sperm before Intracytoplasmic Sperm Injection

Purpose: This study aimed to assess the efficacy and safety of sperm activation with pentoxifylline (PF) for non-obstructive azoospermia (NOA) patients that underwent testicular sperm aspiration (TESA) for intracytoplasmic sperm injection (ICSI) in in vitro fertilization (IVF) program. Methods: A total of 457 patients with 457 TESA- ICSI cycles who identified no motile spermatozoa under through scrutiny were included and divided into two groups. 121 cycles without PF treatment were recorded as control group. The other 336 cycles with PF treatment were recruited as PF group. The two groups were compared for demographics, routine parameters of IVF treatment, pregnancy rates, and neonatal outcomes. Results: The rates of fertilization, 2PN fertilization, D3 oocyte utilization and good-quality embryo in PF group were significantly higher than the control group (P &lt; 0.05). Moreover, PF significantly reduced the total fertilization failure cycle rate, rate of cycles with no transferable embryo and the mean ICSI time per oocyte when compared with the control group (P &lt; 0.05). Although no significant differences were observed between the two groups in the implantation rate, clinical pregnancy rate, miscarriage rates and live birth rate (P &gt; 0.05), significantly increased cumulative live birth rate were found in the PF group (P &gt; 0.05). Neonatal outcomes were comparable between the two groups, and no congenital anomalies were reported in the two groups. Conclusion: Sperm activation with pentoxifylline is beneficial for NOA patients who underwent TESA- ICSI treatment. However, further research with larger groups of couples to assess the long-term effect were still required.

Men's Sleep Quality and Assisted Reproductive Technology Outcomes in Couples Referred to a Fertility Clinic: A Chinese Cohort Study.

BackgroundPoor sleep quality has been linked to lower semen quality, but it is unclear whether this result in decreased fertility. To address this question, we retrospectively evaluated the relationship between men’s sleep quality and treatment outcomes in subfertile couples receiving assisted reproductive technology (ART).Patient Enrollment and MethodsFrom September 2017 to November 2019, 282 subfertile couples referred to a Chinese fertility clinic and eligible for ART procedures were enrolled in our study. Sociodemographic characteristics, life habits, and sleep habits in the year prior to ART were recorded. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). We first divided the patients into two groups based on sleep quality (good sleep: PSQI < 5 and poor sleep: PSQI ≥ 5). Then, the ART outcomes (fertilization rate, good quality embryo rate, implantation rate, positive pregnancy rate, clinical pregnancy rate, live birth rate, miscarriage rate, and birth weight) of each group were analyzed. Finally, multivariate linear and logistic regression analysis were used to examine the relationship between sleep quality (discrete variable or dichotomous variable) and ART outcomes.ResultsThe participants in the poor sleep group showed a lower fertilization rate of 60.13% (543/903) when compared with 67.36% for the good sleep group (902/1339), P < 0.001. The global PSQI score had a significant influence on birth weight (β, −63.81; 95% CI, −119.91- −8.52; P = 0.047), and live birth rate (OR, 0.88; 95% CI, 0.78- 0.99; P = 0.047) after adjusting for the interfering factors. Men’s sleep quality was unrelated to good quality embryos rate, implantation rate, positive pregnancy rate, clinical pregnancy rate, or miscarriage rate.ConclusionMen’s sleep quality was positively associated with fertilization rate, birth weight, and live birth rate among couples undergoing ART.

Cumulative live birth rates after IVF/ICSI cycles with sperm prepared by density gradient centrifugation vs. swim-up: a retrospective study using a propensity score-matching analysis

BackgroundDensity gradient centrifugation (DGC) and swim-up (SU) are the two most widely used sperm preparation methods for in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). However, existing comparisons of IVF/ICSI outcomes following these sperm preparation methods are insufficient and controversial.MethodsThis retrospective study included all first autologous IVF and ICSI cycles performed between March 1, 2016, and December 31, 2020 in a single university-based center. A total of 3608 cycles were matched between DGC and SU using propensity score (PS) matching for potential confounding factors at a ratio of 1:1. The primary outcome was the cumulative live birth rate (cLBR) per aspiration.ResultsPS matching provided 719 cycles after DGC and 719 cycles after SU. After adjusting for confounders, the recovery rate, progressive motility rate after sperm preparation, fertilization rate, good-quality embryo rate, and blastocyst formation rate were similar between the DGC and SU groups. The cLBR (odds ratio [OR] = 1.143, 95% confidence interval [CI]: 0.893–1.461) and LBR per transfer (OR = 1.082, 95% CI: 0.896–1.307) were also not significantly different between the groups. Furthermore, no significant differences were found in all of the laboratory and clinical outcomes following conventional IVF or ICSI cycles between the two groups. However, a significantly higher fertilization rate (β = 0.074, 95% CI: 0.008–0.140) was observed when using poor-quality sperm in the DGC group than in the SU group.ConclusionsSperm preparation using DGC and SU separately resulted in similar IVF/ICSI outcomes. Further studies are warranted to compare the effects of these methods on IVF/ICSI outcomes when using sperm from subgroups of different quality.

Ефективність ембріологічного етапу екстракорпорального запліднення в пацієнток із прогнозованою слабкою відповіддю яєчників

Purpose - to show the efficacy of the embryological stage of in vitro fertilisation (IVF) in women with infertility and predicted poor ovarian response to stimulation with various gonadotropins. Materials and methods. This article analyzes the embryological stage of IVF in 140 women with infertility and predicted poor ovarian response. The main clinical group included 75 women who underwent controlled ovarian superstimulation with urinary gonadotropins in the protocol along with gonadotropin-releasing hormone antagonist. Group II (comparison) included 65 women who underwent stimulation of superovulation as per the similar scheme with recombinant gonadotropins. Oocyte pickups, fertilization, cultivation, and embryo transfer were carried out as per standard techniques. Confirmation or exclusion of biochemical pregnancy was carried out by determining the level of total chorionic gonadotropin in the blood serum 14 days after embryo transfer. When calculating the results, the analysis applied methods that were adopted in medical and biological statistics and described in the Glantz Manual. Data were processed by means of StatSoft Statistica 8.0 software package. Results. Among female patients of Groups I and II - where duration of ovarian stimulation did not exceed 10 days - the average duration of using gonadotropins estimated 8.4±1.3 and 9.5±1.2 days respectively (p&lt;0.05). In patients with a longer administration of drugs compared, the average duration of gonadotropin stimulation was definitely higher when using recombinant gonadotropins, i.e. 12.8±2.0 days versus 10.4±1.4 days (p&lt;0.05). When evaluating the follicle-stimulating hormone (FSH) dose used as part of gonadotropin products compared, it was found that in female patients of Groups I and II - where duration of gonadotropin stimulation did not exceed 10 days - the FSH course dose averaged 2,700±300 IU respectively. With the gonadotropin stimulation lasting for more than 10 days, the FSH dose in Group I increased on average up to 3,000±300 IU; in Group II, it increased on average up to 3,300±300 IU (p&lt;0.05). The number of viable embryos on Day 5-6 of cultivation - in the groups compared - averaged to 5.4±2.1, whereas 4.3±2.3 (p=0.014), and their percentage of the number of obtained zygotes reached 91.2±4.1% and 90.0±5.6% (p=0.041). On Day 5, the process of cultivating viable embryos in the groups decreased down to 4.2±1.5 and 3.6±1.7 (p=0.005), whereas their percentage of the number of obtained zygotes decreased down to 77.2±3.5% and 76.0±4.8% (p=0.012). When conducting the cytomorphological examination of embryos under cultivation, it was found that percentage of good quality embryos in the total pool of embryos aged 5 days was 60.4±13.6% and 54.6±14.2% (p=0.011) respectively, whereas in the total pool of embryos aged 6 days, the percentage was 72.6±14.7% and 68.7±16.4% (p=0.013). Conclusions. The conducted comparative study of the effects of human menopausal gonadotropin and the combination of recombinant FSF + recombinant luteinizing hormone at the pre-transfer stage in all examined female patients with expected poor response to gonadotropins showed that the administration of these drugs was accompanied by definitive differences within a number of parameters of stimulated cycles; in terms of statistics, significant are the conclusions as follows: reducing the stimulation period in women who had duration of gonadotropin for less than 10 days; decreasing the average dose of FSH if the gonadotropin stimulation period lasted less than and more than 10 days; improving the survival rate of embryos aged 5 and 6 days; increasing the percentage of good quality embryos among embryos aged 5 and 6 days. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local ethics committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the author. Key words: infertility, assisted reproductive technologies, controlled ovarian stimulation, urinary gonadotropins, recombinant gonadotropins.

Risk factors for twin pregnancy in women undergoing double cleavage embryo transfer

BackgroundTwo or more embryo transfers have been used to increase the success rate of live birth in traditional in vitro fertilization (IVF) strategy at the expense of increased risks of multiple pregnancy and adverse perinatal outcomes. The decision regarding the elective single embryo transfer or double embryo transfer remains inconclusive. The aim of this study was to investigate the risk factors for twin pregnancy in IVF.MethodsParticipants who underwent their first fresh IVF cycle where two cleavage stage embryos were transferred in Women’s Hospital of Zhejiang University between January 2010 and December 2018 were included in this retrospective cohort study. The primary outcome was twin delivery. Secondary outcomes included preterm birth and low birth weightResultsFifteen thousand four hundred fifty-nine women were available for final analysis, in which 1511 women resulted in twin delivery and 4788 women had singleton delivery. Female age over 35 was associated with reduced rates of twin pregnancy compared with female age at or less than 35 (9.5% vs 25.1%, aRR = 0.38 (0.27. 0.55)). Poor-type endometrium was associated with reduced rates of twin pregnancy (19.2% vs 27.5%, aRR = 0.75 (0.58. 0.96)). Two good-quality embryos for transfer was associated with significantly higher rates of twin pregnancy compared with one good-quality or none good-quality embryo (26% vs 12.8% vs 9.3%, aRR = 0.56 (0.45. 0.70), aRR = 0.44(0.26. 0.74)). Female age over 35 and none or one good-quality embryo for transfer were associated with reduced rate of low birth weight and preterm birth.ConclusionWomen with age over 35, poor-type endometrium, one good-quality embryo or none good-quality embryo were associated with reduced rate for twin pregnancy.

Early Compaction Might Be a Parameter to Determine Good Quality Embryos and Day of Embryo Transfer in Patients Undergoing Intracytoplasmic Sperm Injection

Introduction: Compaction is the first event in embryo morphogenesis. Blastocyst transfer on day five or six has been widely performed in the last decade. We investigated the clinical value of early compaction on day three for evaluation of the transferred embryo quality and pregnancy.Methods: Four hundred patients with female factor infertility and 776 fresh embryo transfers were included. Two groups were formed: Early compaction group had embryo transfer with at least one day-three embryo exhibiting early compaction. Transferred embryos without early compaction comprised the control group. Embryo transfer was performed on day three or five after the assessment of embryo compaction by a time-lapse technology system. Each patient underwent only a single cycle of embryo transfer. We analyzed fertilization, pregnancy, and live birth rates.Results: We detected significantly higher numbers of the retrieved oocytes, metaphase II (MII) oocytes, and fertilized oocytes in the early compaction group. Moreover, the transfer of the early compacting embryos on day three resulted in higher pregnancy and live birth rates.Conclusion: Our data suggest that early compaction might be a factor to determine good quality embryos and embryo transfer day.

Decreased fatty acids induced granulosa cell apoptosis in patients with diminished ovarian reserve.

To investigate whetherfatty acid changes in granulosa cells (GCs) underly the pathogenic mechanisms of diminished ovarian reserve (DOR). GCs were obtained from patients with DOR (n = 70) and normal ovarian reserve (NOR, n = 70). Analysis of fatty acids changes in GCs was then analyzed. Patients with DOR had significantly lower levels of antral follicle count and anti-Mullerian hormone and higher levels of follicle-stimulating hormone compared with NOR patients (P < 0.001). The good-quality embryo rate was notably decreased in DOR patients (51.99 vs 39.52%, P < 0.05). A total of 15 significantly decreased fatty acids in GCs from patients with DOR. The ATP levels were markedly lower in DOR patients than in NOR patients (39.07 ± 12.89 vs 23.21 ± 13.69%, P < 0.05). Mitochondrial membrane potential decreased in DOR patients (P < 0.01). In GCs from DOR patients, the β-oxidation genes (HADHA and ACSL) and DNA repair genes (PRKDC and RAD50) were significantly downregulated (P < 0.05). The γH2AX foci/nucleus ratio in DOR patients markedly increased relative to that of NOR patients (0.31 ± 0.03 vs 0.87 ± 0.07, P < 0.001). Meanwhile, the apoptosis rate of GCs was significantly higher in DOR patients (6.43 ± 2.11 vs 48.06 ± 6.72%, P < 0.01). GC apoptosis resulting from the decrease of fatty acids, and associated with reduced ATP production and DNA damage, may contribute tothe pathogenic mechanisms responsible forDOR.

The effect of transferring a poor-quality embryo together with a good-quality embryo on the singleton birth weight: A retrospective cohort study

BackgroundEmbryo quality may affect birth weight among neonates born through assisted reproductive technology. There are very limited studies assessing the adverse effect of transferring a poor-quality embryo with a good-quality one on neonatal outcomes.ObjectiveThe aim of this study was to evaluate the effect of double embryo transfer (DET) with one good-quality embryo (GQE) plus a poor-quality one on the birth weight of newborns conceived by in vitro fertilization in both fresh and frozen-thawed embryo transfer cycles.Materials and Methods This study was conducted at Yazd Reproductive Sciences Institute, Yazd, Iran. A total of 626 women were classified into three groups according to the embryo quality: single embryo transfer with a GQE (group A); DET using two GQEs (group B); and DET using one good-quality and one poor-quality embryo (group C). The primary outcome was singleton birth weight which was compared between the three groups among fresh and frozen-embryo transfer cycles. A comparative analysis was also performed regarding the effect of vitrification procedures on neonatal birth weight within each of the three embryo quality-based groups.ResultsThe mean birth weight and the rate of preterm birth were similar between the three groups (p = 0.45 and 0.32, respectively). There were also no significant differences found in the vitrification comparative analysis between and within the groups with regard to birth weight.ConclusionOur results showed that a poor-quality embryo did not have a significant influence on a good-quality one regarding neonatal birth weight when transferred together.

Comparative analyses in transcriptome of human granulosa cells and follicular fluid micro-environment between poor ovarian responders with conventional controlled ovarian or mild ovarian stimulations

BackgroundBoth mild and conventional controlled ovarian stimulation are the frequently used protocols for poor ovarian responders. However, there are some debates about which treatment is better. Moreover, little is known about the follicular physiology after the two ovarian stimulation protocols. This study was intended to investigate the features in granulosa cells and follicular fluid micro-environment after the two different ovarian stimulation protocols in poor responders.MethodsGranulosa cells RNA were sequenced using Illumina Hiseq technology. Specific differently expressed genes and proteins were verified by real-time quantitative PCR and Western blot analysis. Moreover, hormone and cytokine concentrations in the follicular fluid were measured by electrochemiluminescence immunoassay and enzyme-linked immunoabsorbent assay. The correlation between the results of molecular experiments and the laboratory outcomes were analyzed by Spearman correlation analysis.ResultsThe differentially expressed genes between the two groups were involved in 4 signaling pathways related to the follicular development; three proteins pertinent to the TGF-β signaling pathway were expressed differently in granulosa cells between the two, and the constituents in the follicular fluid were also different. Further, a correlation between the TGF-β signaling pathway and the good-quality embryo was observed.ConclusionsThe present study made a comparison for the first time in the transcriptome of human granulosa cells and the follicular fluid micro-environment between poor responders with the conventional controlled ovarian stimulation or the mild ovarian stimulation, showing that the TGF-β signaling pathway may correlate with the good-quality of embryos in the mild group, which may be instrumental to the choice of optimal management for IVF patients.

Effect of Vitamin D Supplementation on In Vitro Fertilization Outcomes: A Trial Sequential Meta-Analysis of 5 Randomized Controlled Trials.

Despite numerous studies indicating an imperative role of vitamin D for reproduction, the importance of vitamin D supplementation on in vitro fertilization (IVF) outcomes remains controversial. We therefore performed this meta-analysis to investigate the IVF outcomes of vitamin D supplementation in infertile women with vitamin D deficiency. We systematically searched PubMed, Embase and the Cochrane library for identifying all relevant studies published before August 2021. Pregnancy rate was defined as the primary outcome while good quality embryo, fertilization rate, ongoing pregnancy, and miscarriage were secondary outcomes. We used Review Manager 5.3 (RevMan) to conduct meta-analysis and examined the robustness of the primary outcome by trial sequential analysis. Five studies were included in the final analysis and it suggested that vitamin D supplementation was associated with improved chemical pregnancy rate (risk ratio [RR] = 1.53, 95% confidence interval [CI] = 1.06 to 2.20, p = 0.02) but not benefited in improving clinical pregnancy rate (RR = 1.34, 95% CI = 0.81 to 2.24, p = 0.25) and all secondary outcomes. Trial sequential analysis suggested further studies are needed to confirm this conclusion. We concluded that vitamin D supplementation should be prescribed to improve chemical pregnancy in infertile women with vitamin D deficiency and more studies are required to further confirm this finding.

Associations of sleep characteristics with outcomes of IVF/ICSI treatment: a prospective cohort study.

Are sleep characteristics associated with outcomes of IVF/ICSI treatment? Nocturnal sleep <7 h/night and disturbed sleep are related to impaired oocyte and embryo yield, while longer nocturnal sleep might reduce the chance of a successful pregnancy, and the associations between nocturnal sleep duration and IVF/ICSI outcomes are modified by maternal age and subjective sleep quality. Disturbed sleep and circadian rhythm contribute to impaired fecundity in the general population, but the effects of sleep characteristics on IVF/ICSI outcomes are largely unknown. This study was conducted among 1276 women undergoing IVF/ICSI treatment between December 2018 and September 2019 based on the Tongji Reproductive and Environmental cohort. Owing to the limited number of multiple cycles, we included only the outcomes of their first IVF/ICSI cycle in the current analysis. Data on sleep characteristics were collected via questionnaires on the day of oocyte retrieval. IVF/ICSI outcomes were abstracted from medical records. Quasi-Poisson, quasi-binomial or logistic regression models were used to assess the relations between sleep characteristics and reproductive outcomes after adjusting for relevant confounders. We also performed stratified analyses by subjective sleep quality (good versus poor) and maternal age (≤30 versus >30 years). Compared with women who slept 7 to <8 h/night, those who slept <7 h/night exhibited decreases in the number of retrieved and mature oocytes of 11.5% (95% CI: -21.3%, -0.48%) and 11.9% (95% CI: -22.4%, -0.03%), respectively. A mid-sleep time (MST) earlier than 2:21 a.m. (<2:21 a.m.) or later than 3:00 a.m. (≥3:00 a.m.) and poor subjective sleep quality were inversely associated with the fertilization rate. Women who had trouble falling asleep more than three times per week had a lower number of mature oocytes (-10.5%, 95% CI: -18.6%, -1.6%), normal fertilized oocytes (-14.8%, 95% CI: -23.7%, -4.8%) and good-quality embryos (-15.1%, 95% CI: -25.4%, -3.5%) than those who had no such trouble. In addition, women who slept 9 to <10 h/night had a lower chance of clinical pregnancy compared to women who slept 7 to <8 h/night (odds ratio = 0.65, 95% CI: 0.44, 0.98). In the stratified analyses, the positive associations of nocturnal sleep duration with the number of good-quality embryos and fertilization rate existed only among the women with poor subjective sleep quality (P for interaction = 0.02 and 0.03, respectively). Additionally, we found that the positive associations of nocturnal sleep duration with implantation or clinical pregnancy only existed among women aged over 30 years (P for interaction = 0.04 and 0.01, respectively). Sleep characteristics are self-reported, which may lead to misclassification. MST serves as a proxy of chronotype and may be non-differentially misclassified resulting in an underestimate of the association of interest. Measuring sleep characteristics on the day of oocyte retrieval may lead to bias. Chance findings cannot be excluded because of the limited number of women with <7 h or ≥10 h nocturnal sleep and multiple testing. Our results may be biased by other confounders and may not be generalizable to women of other ethnicities. Unhealthy sleep characteristics, including short nocturnal sleep, inappropriate sleep time, poor subjective sleep quality and having trouble falling asleep, may impair oocyte quantity and its potential to mature or be fertilized. Long nocturnal sleep might reduce the chance of clinical pregnancy among infertile females, especially women younger than 30 years old. Prolonged nocturnal sleep duration may be a potential beneficial behavior for improving IVF/ICSI outcomes for women aged over 30 years and women with poor subjective sleep quality, which requires further investigation. This work was supported by the National Natural Science Foundation of China (81771654) and the National Key R&D Program of China (No. 2018YFC1004201). There are no conflicts of interest to declare. N/A.

Evaluation of IL-1β and TNF-α level in endometrial flush in patients with recurrent implantation failure

Infertility is defined as the inability to conceive within a year of regular unprotected intercourse affecting one in six couples. The most common causes of infertility are ovulatory dysfunction, male factor infertility, and tubal disease [1]. Unexplained Infertility (UI) and Recurrent Implantation Failure (RIF) are diagnoses based on failed pregnancy attempts with current infertility treatment options. UI is diagnosed when testing is inconclusive and RIF is diagnosed after three failed In Vitro Fertilization (IVF) cycles. UI is the absence of conception despite 12 months of unprotected intercourse, not explained by anovulation, poor sperm quality, tubal pathology or other known cause of infertility. RIF is defined by three failed IVF cycles in which one or two high-quality embryos are transferred in each cycle or by two failures in oocyte donor recipients after the transfer of good quality embryos [1]. UI is a common cause of infertility affecting 10-30% of infertile couples [2], while RIF is present in around 10% of in vitro fertilization (IVF) cycles [3].

IVF Outcome in Patients with Different Stages of Endometriosis: Can AMH Be a Predictor?

Background and Objectives: The role of Anti Mullerian Hormone (AMH) in determining the outcome of in vitro fertilization (IVF) in endometriosis has been controversial. This study was conducted to assess whether AMH can predict poor response in endometriosis patients undergoing IVF and to compare the IVF outcomes among the different stages of endometriosis. Methodology: A retrospective study was conducted among 90 endometriosis patients undergoing IVF using the flexible antagonist protocol from January 2016 to December 2018 at DY Patil Medical College, Navi Mumbai. Serum AMH levels were obtained from different patients, primary outcome being clinical pregnancy rate (CPR) while the secondary outcome included the number of oocytes retrieved, number of mature oocytes obtained, fertilization rates (FR), and number of good quality embryos formed. Data was analyzed with SPSS 16.0. Mann-Whitney U and chi-square tests were used to compare the outcomes of IVF with AMH level in different stages of endometriosis. Receiver Operator Characteristic (ROC) curves were plotted to know the predictive ability of AMH by determining the area under the curve (AUC), P value &lt; 0.05 was considered significant for all statistical tests. Results: AUC was found to be significant for AMH in detecting poor response among those with late staged endometriosis but with poor accuracy (AUC = 0.65, P = 0.02∗). Considering a median AMH level of 1.24 ng/mL with sensitivity and specificity of &gt; 60%, the primary and secondary outcomes were significantly higher among those with median AMH levels of more than 1.24 ng/mL compared to those with the median ≤ 1.24 ng/mL. The significance, however, was mainly found in the late stages of endometriosis (P &lt; 0.05). Fertilization rates, good quality embryos, and CPR did not vary with AMH levels among those with early stages of endometriosis (P &gt; 0.05). The outcomes of IVF did not vary significantly across the different stages of endometriosis except for good quality embryos which were formed in patients with early staged endometriosis (P &lt; 0.05). Conclusion: AMH levels may be a predictor of nonconception with poor accuracy in late stages of endometriosis (III/IV), while good quality embryos were obtained in patients with early stages of endometriosis.

Effects of leukocytospermia on the outcomes of assisted reproductive technology.

Leukocytospermia is one of the common causes of male infertility, and its effects on the clinical outcomes of assisted reproduction are controversial. There are no recommendations for the management of leukocytospermia in cases of assisted reproductive technology (ART). To investigate the impact of leukocytospermia on ART, we retrospectively compared the clinical outcomes in ART couples with or without leukocytospermia and further analysed the impact of the insemination method itself by split insemination treatment in ART couples with leukocytospermia. In this study, leukocytospermia was detected in 133 patients, namely 63 in the conventional in vitro fertilization (IVF) group, 38 in the intracytoplasmic sperm injection (ICSI) group and 32 in the split insemination group. Leukocytospermia has a negative influence on the parameters of semen samples; however, leukocytospermia did not affect the clinical outcomes of IVF or ICSI. Different insemination methods did not affect the fertilization, clinical pregnancy or live birth rates. In the split insemination study, no significant differences in clinical pregnancy and live birth rates between the IVF and ICSI groups were found; however, the numbers of two pronuclei (2PN), available embryos and good‐quality embryos in the ICSI group were higher than those in the IVF group. Leukocytospermia may be a risk factor affecting semen parameters, and more attention should be given to IVF insemination. Leukocytospermia has no significant negative effect on the outcomes of ART. ICSI may obtain better embryos than IVF, but it cannot improve the clinical pregnancy and live birth rates.

MTHFR 677TT is associated with decreased number of embryos and cumulative live birth rate in patients undergoing GnRHa short protocol: a retrospective study

BackgroundWhether MTHFR C677T genotype affects pregnancy outcomes following assisted reproductive technology is conflicting. And the role of MTHFR C677T genotype on cumulative live birth has not been reported. This study aims to investigate the effect of MTHFR C677T genotype on cumulative live birth following in-vitro fertilization and embryo transfer (IVF-ET).MethodsThis is a retrospective cohort study that includes 1173 women undergoing their first IVF-ET. We retrospectively compared the reproductive outcomes among the groups stratified by MTHFR C677T genotypes (677CC, 677CT, 677TT). We performed interaction analysis to detect the factor that interacts with the MTHFR C677T genotype. Poisson regression analyses were used to evaluate the associations between MTHFR C677T genotypes with the number of transferable embryos and the number of good-quality embryos. Cox regression analysis was used to evaluate the association between MTHFR C677T genotypes with cumulative live birth. All regression analyses were adjusted with the confounding factors which may independently impact reproductive outcomes.ResultsThere is a significant interactive effect of MTHFR 677TT genotype with GnRHa protocol on reproductive outcomes (P for interaction<0.05). MTHFR 677TT homozygous mutation was found to impact reproductive outcomes under GnRHa short protocol but not GnRHa long protocol. MTHFR 677TT is significantly associated with decreased number of transferable embryos (p-value=0.028), decreased number of good-quality embryos (p-value=0.005), and decreased cumulative live birth rate (p-value=0.024) in patients undergoing GnRHa short protocol. However, the clinical pregnancy rate, miscarriage rate and live birth rate at the first embryo transfer cycle were not significantly different between the groups under both protocols (p-values>0.05).ConclusionsMTHFR 677TT genotype is associated with decreased number of transferable embryos, decreased number of good-quality embryos, and decreased cumulative live birth rate in the first complete cycle in patients undergoing GnRHa short protocol.

IVF under COVID-19: treatment outcomes of fresh ART cycles.

Study QuestionDoes prior SARS-CoV-2 infection in women undergoing fertility treatments affect the outcomes of fresh ART cycles?Summary AnswerSARS-CoV-2 infection does not affect fresh ART treatment outcomes, except for a possible long term negative effect on oocyte yield (>180 days post infection).What Is Known AlreadyA single previous study suggested no evidence that a history of asymptomatic or mild SARS-CoV-2 infection in females caused impairment of fresh ART treatment outcomes.Study Design, Size, DurationRetrospective cohort study, including all SARS-CoV-2 infected women who underwent fresh ART cycles within a year from infection (the first cycle post infection), between October 2020 and June 2021, matched to non-diagnosed controls.Participants/Materials, Setting, MethodsPatients from two large IVF units in Israel who were infected with SARS-CoV-2 and later underwent fresh ART cycles were matched by age to non-diagnosed, non-vaccinated controls. Demographics, cycle characteristics and cycle outcomes, including oocyte yield, maturation rate, fertilization rate, number of frozen embryos per cycle, and clinical pregnancy rates, were compared between groups.Main Results And The Role Of ChanceOne hundred and twenty-one infected patients and 121 controls who underwent fresh ART cycles were included. Oocyte yield (12.50 versus 11.29; p = 0.169) and mature oocyte rate (78% versus 82%; p = 0.144) in all fresh cycles were similar between groups, as were fertilization rates, number of frozen embryos per cycle and clinical pregnancy rates (43% versus 40%; p = 0.737) in fresh cycles with an embryo transfer. In a logistic regression model, SARS-CoV-2 infection more than 180 days prior to retrieval had a negative effect on oocyte yield (p = 0.018, Slope=-4.08, 95% CI -7.41 – -0.75), although the sample size was small.Limitations, Reasons For CautionA retrospective study with data that was not uniformly generated under a study protocol, no antibody testing for the control group.Wider Implications Of The FindingsThe study findings suggest that SARS-CoV-2 infection does not affect treatment outcomes, including oocyte yield, fertilization and maturation rate, number of good quality embryos, and clinical pregnancy rates, in fresh ART cycles, except for a possible long term negative effect on oocyte yield when retrieval occurs > 180 days post SARS-CoV-2 infection. Further studies are warranted to support these findings.Study funding/competing interest(s)None.Trial registration number0010-21-HMC, 0094-21-ASF

Acupuncture as Treatment for Female Infertility: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background The effects of acupuncture on female infertility remain controversial. Also, the variation in the participant, interventions, outcomes studied, and trial design may relate to the efficacy of adjuvant acupuncture. The aim of the study is to systematically evaluate the efficacy and safety of acupuncture for female with infertility and hopefully provide reliable guidance for clinicians and patients. Methods We searched digital databases for relevant studies, including EMBASE, PubMed, Cochrane Library, and Web of Science, and the Cochrane Library up to April 2021, for randomized controlled trials (RCTs) evaluating the effects of acupuncture on women undergoing IVF and other treatment. We included studies with intervention groups using acupuncture and control groups consisting of no acupuncture or sham (placebo) acupuncture. Primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR). Meta-regression and subgroup analysis were conducted on the basis of ten prespecified covariates to investigate the variances of the effects of adjuvant acupuncture on pregnancy rates and the sources of heterogeneity. Results: Twenty-seven studies with 7676 participants were included. The results showed that the intervention group contributes more in outcomes including live birth rate (RR = 1.34; 95% CI (1.07, 1.67); P < 0.05), clinical pregnancy rate (RR = 1.43; 95% CI (1.21, 1.69); P < 0.05), biochemical pregnancy rate (RR = 1.42; 95% CI (1.05, 1.91); P < 0.05), ongoing pregnancy rate (RR = 1.25; 95% CI (0.88, 1.79); P < 0.05), adverse events (RR = 1.65; 95% CI (1.15, 2.36); P < 0.05), and implantation rate (MD = 1.19; 95% CI (1.07, 1.33); P < 0.05) when compared with the control group, and the difference is statistically significant. In terms of the number of oocytes retrieved, good-quality embryo rate, miscarriages, and ectopic pregnancy rate, the difference between the acupuncture group and the control group was not statistically significant. Conclusions: Our analysis finds a benefit of acupuncture for outcomes in women with infertility, and the number of acupuncture treatments is a potential influential factor. Given the poor reporting and methodological flaws of existing studies, studies with larger scales and better methodologies are needed to verify these findings. More double-blind RCTs equipped with high quality and large samples are expected for the improvement of the level of evidence.

Expression of pro-apoptotic and anti-apoptotic proteins in granulosa cells of women with diminished ovarian reserve.

To evaluate the expressions of caspase-3 and cytochrome c and heat shock protein 70 (Hsp70) in granulosa cells (GCs) from women with normal ovarian reserve (NOR) and diminished ovarian reserve (DOR) undergoing intracytoplasmic sperm injection (ICSI). GCs were collected from 117 infertile women during oocyte retrieval. Patients were classified into four groups as follows: DOR-COC score of 0, DOR-COC score of I, NOR-COC score of 0, and NOR-COC score of I. The caspase-3, cytochrome c, and Hsp70 analyses were performed immunohistochemically in GCs. The ICSI outcomes were evaluated prospectively. The clinical pregnancy and live birth rates were higher in DOR-COC score of I (15, 30.6%; 14, 38.9%) and NOR-COC score of I (19, 38.77%; 19, 52.7%) groups, compared with DOR-COC score of 0 (12, 24.4%; 3, 6.1%) and NOR-COC score of 0 (3, 6.1%; 0%) groups (p = 0.0001; 0.00002), respectively. Caspase-3 and cytochrome c expression levels were higher in DOR-COC score of 0 (23, 65.7%; 25, 71.4%) and NOR-COC score of 0 groups (19, 61.3%; 20, 64.5%), compared with DOR-COC score of I (8, 32%; 9, 36%) and NOR-COC score of I groups (7, 26.9%; 8, 30.8%) (p = 0.00297; p = 0.002), respectively. Lower expression levels of Hsp70 were found in DOR-COC score of 0 (11, 31.4%) and NOR-COC score of 0 groups (10, 32.3%), compared with DOR-COC score of I (16, 64%) and NOR-COC score of I groups (20, 76.9%) (p = 0.001), respectively. Hsp70 expression levels were positively correlated with the number of day 3 good-quality embryo and negatively correlated with estradiol levels in the DOR group. Our data suggest that COC score of 0 is associated with increased expression levels of apoptotic proteins, decreased expression levels of anti-apoptotic protein, and poor ICSI clinical outcomes in women with and without DOR.