Top-quality Embryos Research Articles

Comparative Effectiveness of Mild or Conventional GnRH-Antagonist Protocols for Ovarian Stimulation in Poor Responders (Poseidon Group 4).

Background and Aims: A panel of experts (the Poseidon Group) introduced a new and more detailed stratification for poor ovarian responders in order to predict the prognosis of IVF outcome according to the sensitivity to FSH. However, various arguments about the management strategy of these patients still remain, including the convenience and the cost. Therefore, this study was conducted to compare the efficacy of mild and conventional GnRH antagonist ovarian stimulation prescribed in patients classified in Poseidon Group 4.Methods: This retrospective cohort study included 359 poor responder patients (Poseidon Group 4) treated with mild or conventional GnRH antagonist stimulation regimens from 8/2017 to 7/2019 at Tam Anh Hospital ART Center. The main outcomes were the index of Follicular Output Rate (FORT) or Follicle to Oocyte Index (FOI), the number of day-2 embryos and top-quality embryos obtained. The t-test and Mann–Whitney U test in SPSS v25.0 was used to analyze the continuous data and Chi-squared/Exact test was used for binary variables. Multiple linear regression analysis was done by using Stata versions 15.0 to measure association between primary endpoints with stimulation regimen controlled for covariates and possible confounding factors.Results: In the overall group of poor responders, the conventional GnRH antagonist protocol performed better than the mild protocol. Subsequently, data were analyzed according to the AFC. In women with AFC < 3, no significant differences were observed between the 2 regimens regarding FORT (p = 0.71), FOI (p = 0.12), the number of day-2-embryos (p = 0.052) and the number of top-quality embryos (p = 0.26). In contrast, in women with AFC ≥ 3, mild stimulation regimen resulted in significantly poorer outcome compared to the conventional GnRH antagonist regimen, regarding FORT (p < 0.01), FOI (p < 0.01), the number of day-2-embryos (p < 0.01) and top-quality embryos (p = 0.01).Conclusions: Considering poor responders classified in Poseidon Group 4, both ovarian stimulation regimens resulted in similar outcome for patients with a very low ovarian reserve (AFC < 3). In contrast, the GnRH conventional antagonist protocol with maximum initial FSH dose (300–375 IU/day) and supplementary LH (75–150 IU/day) was more effective than the mild one for patients whose ovarian reserve was less reduced. The Clinical Trial was approved by the Ethnical Biomedical Research Committee Tam Anh General Hospital.

Is There Any Association Between the Number of Oocytes Retrieved, Women Age, and Embryo Development?

While most studies focused on the association between the number of oocytes retrieved and LBR, there is lack of analysis highlighting the effect of the number of oocyte retrieved on top quality embryo (TQE) rate in different age groups. We aimed to study the correlations between the number and ratio of TQE, as assessed by morphology only, according to the number of oocytes retrieved, and to evaluate the impact of patients' age. This was a retrospective study that includes 1639 patients who underwent 2263 IVF cycles between 2016 and 2019. Patients were categorized into four groups according to the number of oocytes retrieved: 1-3, 4-9, 10-14, or > 15 oocytes (OPU groups A-D, respectively). Another classification was according to patient's age < 35, 35-40, and > 40years. Morphologically, TQE (both cleavage stage and blastocyst) was defined as those eligible for transfer or vitrification. TQE was assessed both as a fraction of oocytes retrieved per patients (rate) and the average TQE per number oocytes retrieved category. For all age subgroups, a negative significant association was observed between the number of oocytes retrieved and TQE rate (56.1%, 43.6%, 35.9%, and 34.3% for groups A-D, respectively). The reduction was significant up to 14 oocytes retrieved and plateau thereafter. On the other hand, TQE rate was significantly increased as women age increased, from 36.1% TQE rate in young women (< 35years) to 40.3% for 35-40years to 42.5% in older patients (> 40years). Finally, a linear regression revealed a drop in TQE rate of - 0.5% for every oocyte retrieved, while an increased in TQE rate of + 0.7%, as the women age increased by 1year. While young women are able to recruit more oocyte, including medium/low quality, older women recruit less oocytes, with good quality, as demonstrated by their higher morphologically TQE rate relative to the number of oocyte retrieved.

Influence of cleavage-stage embryo quality on the in-vitro fertilization outcome after single embryo transfer in fresh cycles

ObjectiveEmbryo quality is crucial for determining the outcome of embryo implantation. This study aimed to assess the impact of embryo quality on the outcome of in vitro fertilization/single-embryo transfer (IVF-SET). Materials and methodsThis retrospective study included 2531 fresh IVF-SET cycles, including 277 poor-quality and 2254 top-quality embryos. The clinical pregnancy rate, miscarriage rate, live birth, implantation rate, pregnancy outcome and complication were analyzed and compared. Risk factors associated with miscarriage rate and pregnancy complication were identified using logistics regression analysis. ResultsTop-quality embryos resulted in higher clinical pregnancy rate (30.5% vs. 12.6%, P < 0.001) and live birth rate (23.9% vs. 9.7%, P < 0.001) compared with poor-quality embryos. Logistics regression analysis revealed that embryo quality was not correlated with miscarriage rate (95% CI 0.33–1.89) and pregnancy complications (95% CI 0.12–7.84). Maternal age and body mass index was a risk factor for miscarriage rate (95% CI 1.05–1.22) and pregnancy complication (95% CI 1.01–1.29), respectively. ConclusionClinical miscarriage rate and pregnancy complication were embryo quality independent. Maternal age was the risk factor for miscarriage rate. Embryo quality did not affect miscarriage once a clinical pregnancy is achieved.

Evaluation of extracellular vesicles and gDNA from culture medium as a possible indicator of developmental competence in human embryos.

Human embryos generated in vitro have a high incidence of chromosomal abnormalities that negatively affect pregnancy rate. Embryos generated in vitro secrete extracellular vesicles (EVs) into the culture medium that could be used potentially as indicators of embryo competence. This research aimed to evaluate the concentration and size of EVs and their gDNA content as an indicator of developmental competence in human embryos. Human embryos generated by intracytoplasmic sperm injection (ICSI) were classified morphologically as of either TOP, FAIR or POOR quality. Culture medium and developmentally arrested embryos (which were not able to be used for embryo transfer) were collected. Microvesicles, exosomes (MV/Exo) and apoptotic bodies (ABs) were isolated from culture medium. Nanoparticle tracking analysis (NTA) and array comparative genomic hybridization (aCGH) analysis were performed to evaluate EVs and their gDNA content. From NTA, the diameter (mean) of MVs/Exo from TOP quality embryos was higher (112.17 nm) compared with that of FAIR (108.02) and POOR quality embryos (102.78 nm) (P < 0.05). aCGH analysis indicated that MVs/Exo and ABs carried gDNA with the presence of 23 chromosome pairs. However, when arrested embryos were compared with their respective MVs/Exo and ABs, the latter had an increased rate of chromosomal abnormalities (24.9%) compared with embryos (8.7%) (P < 0.05). In conclusion, the size of EVs from culture medium might be an alternative for evaluating competence of human embryos, however more studies are needed to validate the use of gDNA from EVs as an indicator of embryo competence.

The role of ICSI vs. conventional IVF for patients with advanced maternal age-a randomized controlled trial.

This study aimed to evaluate the role of intracytoplasmic sperm injection (ICSI) in the treatment of non-male factor infertile patients aged ≥ 39. This is a single-center, prospective, randomized controlled clinical trial, between March 2018 and December 2019. Sixty-nine patients were recruited, and sixty patients participated in the study. Their ovaries were randomized prior to the beginning of the ovarian stimulation: the oocytes from one side (n = 257) were allocated to the ICSI (ICSI arm), while those of the contralateral side (n = 258) were allocated to conventional insemination (IVF arm). The fertilization rate per oocyte retrieved, number of zygotes (2PN), and cleavage-stage embryos were assessed and compared between the two study groups. The average number of zygotes (3.1 vs. 2.7 p = 0.45), the fertilization rate (72.4% vs. 65.1% p = 0.38), the average number of cleavage-stage (2.8 vs. 2.4 p = 0.29), and the average top-quality embryos (TQE) cleavage-stage embryos (1.7 vs. 1.6 p = 0.94) were comparable between the two groups. The TQE rate per randomized oocyte (41.2% vs. 41% p = 0.8) was also similar in both groups. ICSI does not improve the reproductive outcomes of advanced-age patients undergoing conventional insemination for non-male factor infertility. NCT03370068.

Dual trigger in normally-responding assisted reproductive technology patients increases the number of top-quality embryos.

ObjectiveThe feasibility of a gonadotropin-releasing hormone agonist (GnRHa) trigger in normal responders is still a matter of debate. The aim of this study was to compare the number of mature oocytes, the number of good-quality embryos, and the live birth rate in normal responders triggered by GnRHa alone, GnRHa and human chorionic gonadotropin (hCG; a dual trigger), and hCG alone.MethodsA retrospective cohort study was conducted at the infertility clinic of a university hospital. Data from 200 normal responders who underwent controlled ovarian hyperstimulation and intracytoplasmic sperm injection with a GnRH antagonist protocol between January 2016 and January 2017 were reviewed. The first study group consisted of patients with cycles triggered by GnRHa alone. The second study group consisted of patients with cycles triggered by both GnRHa and low-dose hCG (a dual trigger). The control group consisted of patients with cycles triggered by hCG alone.ResultsThe groups were comparable in terms of demographics and cycle characteristics. The numbers of total oocytes retrieved and metaphase II oocytes were similar between the groups. The total numbers of top-quality embryos were 3.2±2.9 in the GnRHa group, 4.4±3.2 in the dual-trigger group, and 2.9±2.1 in the hCG group (p=0.014). The live birth rates were 21.4%, 30.5%, and 28.2% in those groups, respectively (p=0.126).ConclusionIn normal responders, a dual-trigger approach appears superior to an hCG trigger alone with regard to the number of top-quality embryos produced. However, no clinical benefit was apparent in terms of live birth rates.

Triclosan exposure and in vitro fertilization treatment outcomes in women undergoing in vitro fertilization

Triclosan (TCS) is a widespread environmental endocrine-disrupting chemical. Animal and in vitro studies suggested that triclosan may affect homesostasis of sex and thyroid hormones and impact on reproduction. Due to limited data derived from human epidemiological studies, this study was performed to examine the association between urinary concentration of triclosan and in vitro reproductive outcomes (methaphase II (MII) oocyte yield, top quality embryo, fertilization rate, implantation rate, and clinical pregnancy) among women from infertility clinic. The study participants were enrolled in an Infertility Center in Poland. A total of 450 women aged 25–45 (n = 674 IVF cycles) provided urine samples. The urinary concentrations of triclosan were evaluated using validated gas chromatography ion-tap mass spectrometry method. Clinical outcomes of IVF treatment were abstracted from patients electronic chart records. Triclosan was detected in urine of 82% of women with geometric mean 2.56 ± 6.13 ng/mL. Urinary concentrations of triclosan were associated with decrease implantation rate (p = 0.03). There were no association between other examined IVF outcomes: MII oocytes, embryo quality, fertilization rate, and exposure to triclosan. As this is one of the first study on this topic, studies among larger and more diverse population are needed to confirm the results.

Granulosa cells apoptosis and follicular fluid hormones: comparison of progestin-primed ovarian stimulation versus GnRH antagonist protocols

Objective To explore the effect of progestin-primed ovarian stimulation protocol (PPOS) on mural granulosa cells (GCs) apoptosis and hormonal profiles in follicular fluid (FF) and efficacy over GnRH antagonist (GnRH-A) protocols. Methods We performed a prospective cohort study from June through August 2017 at a tertiary teaching hospital. 63 Patients meeting our criteria were recruited in this prospective study voluntarily and stratified to PPOS or GnRH-A group randomly. Mural GCs and FF were collected during oocyte retrieval. Apoptosis of GCs was assessed using the Annexin V-affinity assay by flow cytometry and hormonal profiles in FF were measured using electrochemiluminescence. Results A total of 63 women were assessed for eligibility, with 25 cases in PPOS group and 38 in GnRH-A group. Difference of early stage apoptosis rate, late stage apoptosis rate, and total apoptosis rate did not reach statistical significance between groups. Meanwhile, concentrations of hormones in FF were comparable in two groups. No statistically significant differences were observed in number of oocytes retrieved, mature oocyte rate, fertilization rate, and top-quality embryos rate. No patients experienced premature LH surge in both groups during the study. Conclusion Compared to GnRH antagonist protocol, PPOS had comparable laboratory outcomes, GCs apoptosis rate and hormonal profiles in FF. PPOS is an effective and safe alternative option to provide controlled ovarian hyperstimulation (COH).

Does sperm DNA fragmentation have negative impact on embryo morphology and morphokinetics in IVF programme?

Evaluation of sperm integrity may predict the in vitro fertilisation (IVF) outcomes. The aim was to evaluate the relationship between the sperm DNA fragmentation (sDNAf) with embryo morphology and morphokinetic using time-laps monitoring (TLM) and to select the best time points for normalisation in IVF setting. After evaluating the fertilisation and pronuclei (Z) scoring, 328 normally fertilised oocytes were assessed to time of pronuclei fading, time of 2 to 8 discrete cells (t2-t8) and abnormal cleavage patterns, such as multinucleation, direct cleavage, reverse cleavage and fragmentation. Sperm chromatin dispersion (SCD) assay was used for assessment of prepared sperm chromatin status. SCD was categorised into 4 groups of <6.5, 6.5-10.7, 10.7-20.1 and >20.1. The finding showed significant differences in t6 (p=.012), t7 (p=.045), t8 (p=.013) and s1 (p=.001) between 4 SCD groups. When morphokinetic variables were normalised to tPNf, this difference was observed in t2 (p=.003) and t6 (p=.017). Subsequently, the percentage of top quality embryos and Z1 scoring were dependent to the sDNAf rate. In conclusion, tPNf was the best reference time point in IVF cycles. Also, we found high sDNAf rate had no negative impact on embryo morphology and morphokinetics in conventional IVF.

Does a Large (>24 mm) Follicle Yield a Competent Oocyte/Embryo?

Aim: To evaluate the effect of large follicular size (≥24 mm) at day of oocyte retrieval on oocyte/embryo quality. Patients and Methods: A cohort study was conducted in a single tertiary medical center between July 2018 and May 2019. Before ultrasound-guided follicular aspiration, follicles were measured and divided into 2 groups according to their maximal dimensional size: large: ≥24 mm and normal: <24 mm. Microscopic examination of the follicular aspirates was performed by an embryologist. Each follicle aspirated was evaluated for oocyte maturation, oocyte fertilization, and embryo quality. Results: 428 follicles were measured, including 383 (62.81%) in the normal and 45 (14.06%) in the large follicle groups. Oocytes were achieved during aspiration from 297 (75.5%) and 29 (64.4%) of the normal and large follicle groups, respectively (p = 0.05). No in-between group differences were observed in mature oocyte (MII), fertilization, and top-quality embryo (TQE) rates. Nevertheless, once a zygote (2PN) was achieved, a trend toward a higher TQE rate/2PN was found in the large follicle group (16/19 [84.2%] vs. 115/171 [67.3%]; p = 0.062). Conclusion: While a nonsignificant decrease in oocyte recovery rate was found in follicles ≥24 mm, the zygote and TQE per follicle were comparable.

Degenerated oocyte in the cohort adversely affects IVF outcome

The presence of Degenerated Oocyte (DEG) was mostly described after intracytoplasmic sperm injection (ICSI), with fewer reports on DEG at the time of ovum pick-up (OPU). This study aims to assess morphokinetics of embryos cultured in a time-lapse incubator and compare cohorts with and without DEG at OPU. In a retrospective cohort study from January 1, 2016 until September 31, 2017 a total of 399 IVF/ICSI cycles and 2980 embryos were evaluated. In 81 of 399 cycles at least one DEG oocyte was observed at the time of OPU. The remaining 318 cycles with no DEG oocyte were compared as a control group. In the DEG group, significantly more oocytes were collected per patient (12.9 ± 7.2 vs. 10.1 ± 6.1. P < 0.001). Fertilization rate, pregnancy and clinical pregnancy rates were comparable between the two groups, however, the morphokinetics and developmental scores of the embryos were significantly worse in the DEG group, (KID 3.4 ± 1.6 vs. 3.2 ± 1.6 P = 0.002 and ESHRE 1.5 ± 1.1 vs. 1.4 ± 1.0 P = 0.046). Significantly more patients achieved top-quality embryos in the NON DEG group (58.8% vs. 53.0%, P = 0.03), however, comparable delivery rate was achieved in both groups. In the DEG group, the frequency of DEG oocyte per cycle was negatively correlated with pregnancy rate. GnRH agonist protocol and the 17-20G needle used for OPU were significant predictors for the presence of DEG oocyte at OPU. In conclusions DEG oocyte may negatively affect IVF outcome, however, younger patients, and significantly more oocytes collected in the DEG group compensate for the IVF results.

Being on the side of old findings: progesterone elevation on the day of oocyte maturation induction does not affect embryological parameters throughout the blastocyst culture period.

To investigate whether there is any detrimental effect of progesterone elevation (PE) on the day of oocyte maturation induction on embryological development potentials. This retrospective single-center cohort study included a total of 1485 individual intracytoplasmic sperm injection (ICSI) cycles between January 2014 and December 2018. Serum progesterone (P) levels were measured on the day of oocyte maturation induction following the GnRH antagonist suppression protocol. Embryological parameters such as maturation, fertilization rate (FR), top-quality embryo (TQE) formation rate per 2PN on day 3, and excellent-quality blastocyst (EQB) formation rate per 2PN on day 5/6 were recorded. The inclusion criteria for women were an age ≤ 37years, a BMI ≤ 30kg/m2, and access to a total sperm concentration ≥ 2 million. Groups were stratified according to the serum P levels using the cut-off levels of < 0.8ng/ml; 0.8-1.49ng/ml; and ≥ 1.5ng/ml. Peak E2 level and total number of oocytes retrieved were significantly related to PE (p < 0.001). FR did not display a significance difference between groups (p = 0.108). The TQE and the blastulation rates were not affected by PE (p = 0.82 and p = 0.68, respectively). Chi square analysis revealed a significant relationship between PE and the EQB formation rate (p = 0.01). GEE analysis failed to present any statistical significance regarding the effect of PE on neither the TQE nor the EQB formation rates per 2PN [OR 1.07; 95% (0.98-1.16) p = 0.113 and OR 0.93; 95% (0.80-1.07) p = 0.32, respectively]. In accordance with previously published papers, our study could not find any detrimental effect of PE on embryological outcomes throughout the blastocyst culture period.

TIMING OF INITIATING GnRH ANTAGONIST DOWN-REGULATION IN IVF CYCLES AFFECTS CLINICAL OUTCOMES OF PCOS PATIENTS

Whether the timing of use of gonadotropin-releasing hormone (GnRH) antagonist down-regulation for IVF cycles affects pregnancy outcomes of polycystic ovary syndrome (PCOS) patients? Retrospective cohort study of 1008 PCOS patients undergoing first IVF cycles using GnRH antagonist protocol from January, 2014 to December, 2019 According to the dominant follicle size on the day of GnRH antagonist administration, the included patients were divided into three groups: Group A, dominant follicle diameter (DFD) ＜10mm; Group B, 10mm≤DFD ＜14mm; Group C, DFD ≥14mm. The parameters regarding demographic and clinical characteristics, ovarian stimulation characteristics, clinical outcomes including number of oocytes retrieved, top quality embryo number, clinical pregnancy rate, live birth rate, etc were compared among different groups. The age, anti-Mullerian hormone level and body mass index were comparable among different groups. Total FSH dosage of Group A (1492.7IU) was more than Group B (1292.7IU) and Group C (1243.6IU). Group A needed longest FSH stimulation duration and GnRH antagonist duration (9.6days, 5.1days, respectively), then group B (8.9days, 4.8days, respectively), then group C (8.27days, 3.4days, respectively). Progesterone level on HCG day was higher in group B (1.00ng/ml) than in group A (0.88ng/ml) and group C (0.75ng/ml). The number of oocytes retrieved was highest in group B (18.3), then group A (16.3) and the lowest in group C (14.5). The number of fertilization embryos, transferable embryos, top-quality embryos and blastocysts in group B (10.8, 8.7, 7.2, 3.1, respectively) were more than in group C (8.5, 7.2, 5.9, 1.6, respectively), while comparable in group A (9.7, 8.2, 6.8, 3.3, respectively). Following the patients’ first embryo transfer (ET) cycles, although there were no significant differences in the rate of chemical pregnancy, clinical pregnancy nor live birth in fresh or frozen ET cycles, the live birth rate of group C was the lowest (fresh ET, frozen ET: group A, 50.0%, 52.7%;group B, 48.0%, 54.7%;group C, 46.5%, 46.3%, respectively). For PCOS patients, initiating GnRH antagonist when dominant follicle diameter between 10mm to 14mm could reduce FSH dosage, shorten FSH stimulation duration, retrieve more oocytes, get more top-quality embryos and achieve higher live birth rate in IVF cycles.

Perinatal and neonatal outcomes of pregnancies after early rescue intracytoplasmic sperm injection in women with primary infertility compared with conventional intracytoplasmic sperm injection: a retrospective 6-year study

BackgroundEarly rescue intracytoplasmic sperm injection (ICSI) has been used in clinic as appropriate currently. While the outcomes of children born after this method were not well assessed. The purpose of this study was to evaluate the effect of early rescue ICSI on women with primary infertility.MethodsFresh embryo transfer cycles after rescue (n = 214) and conventional (n = 546) ICSI were retrospectively evaluated from women with primary infertility who underwent their first assisted reproductive technology cycles at our center in 2012–2017. The conventional ICSI group was subdivided into ICSI-1 (semen suitable for in vitro fertilization, IVF) and ICSI-2 (poor semen quality) to minimize bias from differences in semen quality. Pregnancy, delivery and neonatal outcomes were compared between groups.ResultsThere was a higher rate of polyspermy and a lower rate of top-quality embryos (TQE) on day 3 for oocytes subject to rescue ICSI compared with conventional ICSI. This reduced the total number of TQE and the number of TQE transferred in the rescue ICSI group. There was no significant difference between groups in clinical pregnancy, ongoing pregnancy, early miscarriage and live birth. For pregnant women, gestational age, route of delivery, risk of preterm birth and gestational diabetes mellitus were also comparable. Neonatal outcomes including sex ratio, birth weight, neonatal intensive care unit admission and birth defects were also similar after rescue and conventional ICSI. Moreover, no differences were observed with the different ICSI subgroups.ConclusionsFor women with primary infertility who have a high risk of IVF fertilization failure (FF), rescue ICSI provides a safe and efficient alternative to minimize FF after initial IVF, but results in fewer TQE on day 3.

Machine learning vs. classic statistics for the prediction of IVF outcomes.

To assess whether machine learning methods provide advantage over classic statistical modeling for the prediction of IVF outcomes. The study population consisted of 136 women undergoing a fresh IVF cycle from January 2014 to August 2016 at a tertiary, university-affiliated medical center. We tested the ability of two machine learning algorithms, support vector machine (SVM) and artificial neural network (NN), vs. classic statistics (logistic regression) to predict IVF outcomes (number of oocytes retrieved, mature oocytes, top-quality embryos, positive beta-hCG, clinical pregnancies, and live births) based on age and BMI, with or without clinical data. Machine learning algorithms (SVM and NN) based on age, BMI, and clinical features yielded better performances in predicting number of oocytes retrieved, mature oocytes, fertilized oocytes, top-quality embryos, positive beta-hCG, clinical pregnancies, and live births, compared with logistic regression models. While accuracies were 0.69 to 0.9 and 0.45 to 0.77 for NN and SVM, respectively, they were 0.34 to 0.74 using logistic regression models. Our findings suggest that machine learning algorithms based on age, BMI, and clinical data have an advantage over logistic regression for the prediction of IVF outcomes and therefore can assist fertility specialists' counselling and their patients in adjusting the appropriate treatment strategy.

Endometriosis Lowers the Cumulative Live Birth Rates in IVF by Decreasing the Number of Embryos but Not Their Quality.

Endometriosis and infertility are closely linked, but the underlying mechanisms are still poorly understood. This study aimed to evaluate the impact of endometriosis on in vitro fertilization (IVF) parameters, especially on embryo quality and IVF outcomes. A total of 1124 cycles with intracytoplasmic sperm injection were retrospectively evaluated, including 155 cycles with endometriosis and 969 cycles without endometriosis. Women with endometriosis had significantly lower ovarian reserve markers (AMH and AFC), regardless of previous ovarian surgery. Despite receiving significantly higher doses of exogenous gonadotropins, they had significantly fewer oocytes, mature oocytes, embryos, and top-quality embryos than women in the control group. Multivariate analysis did not reveal any association between endometriosis and the proportion of top-quality embryo (OR = 0.87; 95% CI [0.66–1.12]; p = 0.3). The implantation rate and the live birth rate per cycle were comparable between the two groups (p = 0.05), but the cumulative live births rate was significantly lower in in the endometriosis group (32.1% versus 50.7%, p = 0.001), as a consequence of the lower number of frozen embryos. In conclusion, endometriosis lowers the cumulative live birth rates by decreasing the number of embryos available to transfer, but not their quality.

Urinary bisphenol A concentrations and in vitro fertilization outcomes among women from a fertility clinic

Bisphenol A (BPA) is a widespread environmental endocrine disrupting chemical. Although many animals and in vitro studies reported that BPA may affect female fertility through the effect on maturing oocytes and meiotic cell division, but the data from human studies are limited and inconclusive. The study was conducted to examine the association between urinary BPA concentration and in vitro reproductive outcomes (metaphase II (MII) oocyte yield, top quality embryo, fertilization rate, implantation rate and clinical pregnancy) among women from an infertility clinic.The study participants were enrolled in the Infertility Center in Poland. 450 women aged 24-44 (n = 674 IVF cycles) provided urine samples. The urinary concentrations of BPA were evaluated using validated gas chromatography ion-tap mass spectrometry method. Clinical outcomes of IVF treatment were abstracted from patients electronic chart records. To assess the relationship between urinary BPA concentrations early examined reproductive outcomes generalized linear mixed models were used.The detection rate of BPA in urine samples was 98% and the geometric mean 1.59 ± 2.15 ng/ml. A significant decrease was observed between urinary concentration of BPA and implantation (p = 0.04) and decreased MII oocyte count (p = 0.03). There was no association between other examined IVF outcomes: embryo quality, fertilization rate and clinical pregnancy and BPA exposure.Exposure to BPA may have a negative effect during the early stages of human development. The studies among the larger and more diverse population are needed to confirm the results.

Optimal numbers of mature oocytes to produce at least one or multiple top-quality day-3 embryos in normal responders.

ObjectiveWe attempted to identify the optimal cutoff numbers of mature oocytes that would produce at least one or multiple top-quality (grade A) day-3 embryos in normal responders undergoing stimulated in vitro fertilization (IVF) cycles.MethodsWe selected 210 fresh IVF cycles performed in 170 infertile women at a single center from January 2014 to November 2019. Four to 14 (total) oocytes were obtained in all cycles after conventional ovarian stimulation. A receiver operating characteristic curve analysis was performed to find the moderate and extreme cutoff numbers of mature oocytes that would produce ≥ 1, ≥ 2, ≥ 3, ≥ 4, and ≥ 5 top-quality embryos.ResultsThe cutoff number of mature oocytes was significantly correlated with the number of top-quality embryos (r = 0.467, p= 0.000). The moderate cutoff number of mature oocytes was ≥ 3, ≥ 5, ≥ 5, ≥ 6, and ≥ 6 for obtaining ≥ 1, ≥ 2, ≥ 3, ≥ 4, and ≥ 5 top-quality embryos, respectively. The extreme cutoff number of mature oocytes was ≥ 9, ≥ 9, ≥ 10, ≥ 10, and ≥ 11 for obtaining ≥ 1, ≥ 2, ≥ 3, ≥ 4, and ≥ 5 top-quality embryos, respectively.ConclusionWe present the optimal cutoff numbers of mature oocytes that would yield ≥ 1, ≥ 2, ≥ 3, ≥ 4, and ≥ 5 top-quality embryos with 95% specificity. Our findings could help infertility clinicians to set target mature oocyte numbers in women undergoing stimulated IVF cycles.

Stop GnRH-Agonist Combined with Multiple-Dose GnRH-Antagonist for Patients with Elevated Peak Serum Progesterone Levels Undergoing Ovarian Stimulation for IVF: A Proof of Concept

Aim: The aim of the study was to examine whether the Stop GnRH-agonist combined with multiple-dose GnRH-antagonist protocol may overcome progesterone elevation during the late follicular phase. Patients and Methods: A cohort historical, proof of concept study consisting of 11 patients with progesterone elevation (>3.1 nmol/L) during conventional IVF/intracytoplasmic sperm injection (ICSI), who underwent a subsequent Stop GnRH-agonist combined with multiple-dose GnRH-antagonist ovarian stimulation (OS) protocol, within 3 months of the previous failed conventional IVF/ICSI cycle. Results: The Stop GnRH-agonist combined with multiple-dose GnRH-antagonist COH protocol revealed significantly lower peak progesterone levels, with significantly higher numbers of follicles >13 mm in diameter on the day of hCG administration, oocytes retrieved, mature oocytes, and top-quality embryos, with an acceptable clinical pregnancy rate (18.2%). Conclusions: The combined Stop GnRH-ag/GnRH-ant OS protocol is a valuable tool in the armamentarium for treating patients with progesterone elevation during the late follicular phase. Further large prospective studies are needed to validate our observation and to characterize the appropriate patients’ subgroup, which might benefit from the combined Stop GnRH-ag/GnRH-ant COH protocol.

Spermatozoa retrieved by electroejaculation: Should we prefer fresh or cryopreserved spermatozoa for intracytoplasmic sperm injection?

We aim to evaluate our experience, comparing intracytoplasmic sperm injection (ICSI) outcomes of cycle using fresh versus thawed electroejaculated spermatozoa. All consecutive couples undergoing ICSI cycles using electroejaculated spermatozoa, during a 16-year period, were evaluated. Embryological/laboratory variables of the ICSI cycles were assessed and compared between those utilising fresh (fresh group) versus thawed (thawed group) electroejaculated spermatozoa. Fifty-seven couples were evaluated, 30 used a fresh electroejaculated spermatozoa in 55 ICSI cycles, while 27 used a thawed sperm sample in 41 ICSI cycles. There were no in-between group differences in the mean numbers of oocytes retrieved per oocyte retrieval nor the percentage of MII oocytes. The fresh group demonstrated significantly higher fertilisation (71.5% vs. 64.1%, respectively, p<.05), top-quality embryos (66.5% vs. 54.9%, respectively, p<.02), clinical pregnancy per transfer (41.3% and 21.2%, respectively, p<.05) and cumulative clinical pregnancy (58.2% vs. 26.8%, respectively, p<.001) rates, as compared to the thawed group. Independent of the source of spermatozoa used, no pregnancy was achieved following ICSI utilising immotile spermatozoa. In conclusion, ICSI cycles using ejaculated spermatozoa of patients suffering from neurologic or psychogenic anejaculation are reassuring. The use of fresh ejaculated spermatozoa retrieved on the day of the female spouse oocyte retrieval might improve outcome. Whenever a thawed electroejaculated spermatozoa yield no motile spermatozoa, emergency electroejaculation is mandatory.