Does growth hormone supplementation of in vitro fertilization/intracytoplasmic sperm injection improve cumulative live birth rates in women with poor embryonic development in the previous cycle?

BACKGROUND: Growth hormone (GH) has been proposed as an adjunct in in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles, especially in women with poor ovarian response. However, it is unclear whether GH supplementation is effective in women with poor embryonic development in the previous IVF cycle. The aim of this study was to evaluate the effectiveness of GH supplementation in IVF/ICSI cycles in women with poor embryonic development in the previous cycle. METHODS: This is a retrospective cohort study from a public fertility center in China, in which we performed propensity score-matching (PSM) for female age and AFC in a ratio of 1:1. We compared the cumulative live birth rate per started cycle, as well as a series of secondary outcomes. We included 3,043 women with poor embryonic development in the previous IVF/ICSI cycle, of which 1,326 had GH as adjuvant therapy and 1,717 had not. After PSM, there were 694 women in each group. RESULTS: After PSM, multivariate analyses showed the cumulative live birth rate to be significantly higher in the GH group than the control group [N = 694, 34.7% vs. N = 694, 27.5%, risk ratio (RR): 1.4 (95%CI: 1.1-1.8)]. Endometrial thickness, number of oocytes retrieved, number of embryos available, and number of good-quality embryos were significantly higher in the GH group compared to controls. Pregnancy outcomes in terms of birth weight, gestational age, fetal sex, preterm birth rate, and type of delivery were comparable. When we evaluated the impact of GH on different categories of female age, the observed benefit in the GH group did not appear to be significant. When we assessed the effect of GH in different AFC categories, the effect of GH was strongest in women with an AFC5-6 (32.2% versus 19.5%; RR 2.0; 95% CI 1.2-3.3). CONCLUSIONS: Women with poor embryonic quality in the previous IVF/ICSI cycles have higher rates of cumulative live birth with GH supplementation.

Endometrium development patterns and BMI groups among in vitro fertilization patients; prognostic aspects.

Introduction: The impact of the obesity pandemic on female reproductive capability is a factor that needs to be investigated. In addition, the link between endometrial thickness and in vitro fertilization (IVF) outcomes is contentious. Goal: Our goal was to analyze the association among endometrium development, hormone levels, embryo quality, clinical pregnancy, anamnestic parameters, and body mass index (BMI) in women receiving IVF treatment. Patients and methods: 537 participants undergoing IVF/ICSI cycles with successful oocyte retrieval were enrolled. Subjects were divided into four BMI based groups: underweight (UW; n=32), normal weight (NW; n=324), overweight (OW; n= 115), obesity (OB; n=66). Anthropometric and anamnestic parameters, characteristics of stimulation, endometrial thickness on the day of hCG injection, at puncture, at embryo transfer, FSH, LH, AMH, partner's age and the semen analysis indicators, embryo quality, clinical pregnancy, were recorded and analyzed. Support Vector Machine (SVM) was built to predict potential pregnancies based on medical data using 22 dimensions. Results: In accordance with BMI categories, when examining pregnant/non-pregnant division, the average age of pregnant women was significantly lower in the UW (30.9 ± 4.48 vs. 35.3 ± 5.49 years, p=0.022), NW (34.2 ± 4.25 vs. 36.3 ± 4.84 years, p<0.001), and OW (33.8 ± 4.89 vs. 36.3 ± 5.31 years, p=0.009) groups. Considering FSH, LH, and AMH levels in each BMI category, a statistically significant difference was observed only in the NW category FSH was significantly lower (7.8 ± 2.99 vs. 8.6 ± 3.50 IU/L, p=0.032) and AMH (2.87 ± 2.40 vs. 2.28 ± 2.01 pmol/L, p=0.021) was higher in pregnant women. There were no further statistically significant differences observed between the pregnant and non-pregnant groups across any BMI categories, especially concerning endometrial development. Surprisingly, BMI and weight correlated negatively with FSH (r=-0.252, p<0.001; r=-0.206, p<0.001, respectively) and LH (r= -0.213, p<0.001; r= -0.195, p<0.001) in the whole population. SVM model average accuracy on predictions was 61.71%. Discussion: A convincing correlation between endometrial thickness development and patients' BMI could not be substantiated. However, FSH and LH levels exhibited a surprising decreasing trend with increasing BMI, supporting the evolutionary selective role of nutritional status. Our SVM model outperforms previous models; however, to confidently predict the outcome of embryo transfer, further optimization is necessary.

Microdissection testicular sperm extraction in non-obstructive azoospermic patients with solitary testis: a retrospective case-control study.

Obtaining sperm from the testis surgically and using these sperm with the intracytoplasmic sperm injection technique, has opened the way for the possibility of biological fathering in men with non-obstructive azoospermia (NOA). We aimed to evaluate our sperm retrieval rate (SRR) by microdissection testicular sperm extraction (micro-TESE) in NOA patients with solitary testis. In this retrospective case-control study, fortyfive patients with NOA who had a congenital or acquired solitary testis were included, between September 2003 and January 2022. These patients were randomly matched with patients with NOA who had bilateral testes, using a 1:3 matching ratio. We found that SRR by micro-TESE in patients with solitary testis was similar to NOA patients with bilateral testis (51.1% vs. 50.4%). Age, infertility period, ejaculate volume, serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone, history of varicocelectomy, history of orchiopexy, testicular stimulation therapy before micro-TESE, testicular volume, genetic status, TESE side, micro-TESE success, complications and histopathological evaluation results of both groups were evaluated, there was a statistically significant difference in only serum FSH and LH levels. There was no difference between the groups in terms of complications and hormonal effects in the early postoperative period. Micro-TESE in NOA patients with solitary testis has similar sperm retrieval and complication rates as NOA patients with bilateral testis.

Successful pregnancy with intracytoplasmic sperm injection after bacterial contamination of embryo culture in in vitro fertilization: a case report.

BACKGROUND: Bacterial infection of embryo culture medium is rare but may be detrimental. The main source of embryo culture contamination is semen. Assisted reproduction centers currently lack consensus regarding the methods for preventing and managing embryo culture infection. In our recent case, a successful pregnancy was achieved with intracytoplasmic sperm injection after failed conventional in vitro fertilization owing to bacterial contamination. CASE PRESENTATION: We present a case report of two consecutive in vitro fertilization-intracytoplasmic sperm injection cycles with photo and video documentation of the bacterial growth. A 36-year-old Hungarian woman and her 37-year-old Hungarian partner came to our department. They had two normal births followed by 2 years of infertility. The major causes of infertility were a closed fallopian tube and asthenozoospermia. Bacterial infection of the embryo culture medium was observed during in vitro fertilization and all oocytes degenerated. The source was found to be the semen. To prevent contamination, intracytoplasmic sperm injection was used for fertilization in the subsequent cycle. Intracytoplasmic bacterial proliferation was observed in one of the three fertilized eggs, but two good-quality embryos were successfully obtained. The transfer of one embryo resulted in a successful pregnancy and a healthy newborn was delivered. CONCLUSION: Intracytoplasmic sperm injection may be offered to couples who fail conventional in vitro fertilization treatment owing to bacteriospermia, as it seems to prevent infection of the embryo culture. Even if bacterial contamination appears, our case encourages us to continue treatment. Nevertheless, the development of new management guidelines for the prevention and management of bacterial contamination is essential.

Decreased embryo developmental potential and lower cumulative pregnancy rate in men with multiple morphological abnormalities of the sperm flagella.

Objective: Multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by abnormal flagellar phenotypes, which is a particular kind of asthenoteratozoospermia. Previous studies have reported a comparable intracytoplasmic sperm injection (ICSI) outcome in terms of fertilization rate and clinical pregnancy rate in patients with MMAF compared with those with no MMAF; however, others have conflicting opinions. Assisted reproductive technology (ART) outcomes in individuals with MMAF are still controversial and open to debate. Methods: A total of 38 patients with MMAF treated at an academic reproductive center between January 2014 and July 2022 were evaluated in the current retrospective cohort study and followed up until January 2023. Propensity score matching was used to adjust for the baseline clinical characteristics of the patients and to create a comparable control group. The genetic pathogenesis of MMAF was confirmed by whole exome sequencing. The main outcomes were the embryo developmental potential, the cumulative pregnancy rate (CLPR), and the cumulative live birth rate (CLBR). Results: Pathogenic variants in known genes of DNAH1, DNAH11, CFAP43, FSIP2, and SPEF2 were identified in patients with MMAF. Laboratory outcomes, including the fertilization rate, 2PN cleavage rate, blastocyst formation rate, and available blastocyst rate, followed a trend of decline in the MMAF group (p < 0.05). Moreover, according to the embryo transfer times and complete cycles, the CLPR in the cohort of MMAF was lower compared with the oligoasthenospermia pool (p = 0.033 and p = 0.020, respectively), while no statistical differences were observed in the neonatal outcomes. Conclusion: The current study presented decreased embryo developmental potential and compromised clinical outcomes in the MMAF cohort. These findings may provide clinicians with evidence to support genetic counseling and clinical guidance in specific patients with MMAF.

Effect of diminished ovarian reserve on the outcome of fresh embryo transfer in IVF/ICSI cycles among young women: A retrospective cohort study.

OBJECTIVE: This study aims to investigate the effect of diminished ovarian reserve (DOR) on the clinical outcomes and maternal and infant safety of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) procedures in young women aged ≤ 35 years. METHODS: A retrospective cohort study was performed to analyze the clinical data of 4,203 infertile women aged ≤ 35 years who underwent fresh embryo transfer (ET) in IVF/ICSI cycles. The data were collected from their initial visits to Fujian Maternity and Child Health Hospital between January 2015 and January 2022. Based on their ovarian reserve, the participants were categorized into two groups: DOR group (n = 1,027) and non-DOR group (n = 3,176). A propensity score matching (PSM) method was employed to ensure a relatively balanced distribution of covariates. The primary outcome assessed in this study was the live birth rate, while the secondary observation indicators included rates of high-quality embryo development, blastocyst formation, clinical pregnancy, and miscarriage, along with perinatal complications, neonatal birth weight, and the incidence of low birth weight (LBW). RESULTS: The DOR group showed notably lowered rates of blastocyst formation (59.8% vs. 64.1%), embryo implantation (29.8% vs.33.3%), clinical pregnancy (47.9% vs. 53.6%), and live birth (40.6% vs. 45.7%) compared to the non-DOR group (all P < 0.05). However, no statistically significant differences were observed in the high-quality embryo rate, miscarriage rate, perinatal complications, neonatal birth weight, or LBW incidence in infants between both groups (all P > 0.05). CONCLUSION: DOR has been found to reduce both clinical pregnancy and live birth rates in young females undergoing fresh ET in IVF/ICSI cycles. However, this reduction does not increase the risk of perinatal complications or LBW of infants through live birth cycles.

Autologous platelet-rich plasma for assisted reproduction.

BACKGROUND: Autologous platelet-rich plasma (PRP) consists of plasma and a concentrate of platelets extracted from fresh whole blood of the person being treated. Research has suggested that intrauterine or intraovarian infusion/injection of PRP before embryo transfer may improve endometrial receptivity and response to ovarian stimulation in women undergoing assisted reproduction. We compared these interventions to standard treatment, placebo, or other interventions (mechanical or pharmacological). OBJECTIVES: To assess the effectiveness and safety of intrauterine and intraovarian infusion/injection of platelet-rich plasma in infertile women undergoing assisted reproductive technology cycles. SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility Group's Specialised Register, CENTRAL, MEDLINE, Embase, and the Epistemonikos database in January 2023. We also searched the reference lists of relevant articles and contacted the trial authors and experts in the field for any additional trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated the application of PRP in the uterine cavity, ovaries, or both versus no intervention, placebo, or any other intervention (either mechanical or pharmacological) in women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles. DATA COLLECTION AND ANALYSIS: We followed standard methodological procedures recommended by Cochrane, including use of the updated risk of bias tool (RoB 2). The primary outcomes were live birth (or ongoing pregnancy) and miscarriage. The secondary outcomes were clinical pregnancy, complications of the procedure, multiple pregnancy, ectopic pregnancy, fetal growth restriction, preterm delivery, and fetal abnormality. We estimated the average effect of the interventions by fitting a Der Simonian-Laird's random-effects meta-analysis model. We reported pooled odds ratios (ORs) with 95% confidence intervals (CIs). We restricted the primary analyses to trials at low risk of bias for the outcomes and performed sensitivity analyses that included all studies. MAIN RESULTS: We included 12 parallel-group RCTs that recruited a total of 1069 women. We identified three different comparison groups. Using GRADE, we assessed the certainty of evidence as very low for almost all outcomes. Intrauterine injection/infusion of platelet-rich plasma versus no intervention or placebo Nine studies evaluated intrauterine PRP versus no intervention or placebo. Eight included women with at least two or three previous implantation failures. Only one was assessed at low risk of bias for each outcome. This study provided very low-certainty evidence about the effect of intrauterine PRP injection versus no intervention on live birth (OR 1.10, 95% CI 0.38 to 3.14; 94 women) and miscarriage (OR 0.96, 95% CI 0.13 to 7.09; 94 women). If the likelihood of live birth following no intervention is assumed to be 17%, then the likelihood following intrauterine PRP would be 7% to 40%; and if the risk of miscarriage following no intervention is 4%, then the risk following intrauterine PRP would be 1% to 24%. When we analyzed all studies (regardless of risk of bias), we found very low-certainty evidence about the effect of intrauterine PRP compared with placebo or no intervention on live birth or ongoing pregnancy (OR 2.38, 95% CI 1.16 to 4.86; I² = 54%; 6 studies, 564 women) and miscarriage (OR 1.54, 95% CI 0.59 to 4.01; I² = 0%; 5 studies, 504 women). The study at low risk of bias provided very low-certainty evidence about the effect of intrauterine PRP compared with no intervention on clinical pregnancy (OR 1.55, 95% CI 0.64 to 3.76; 94 women) and ectopic pregnancy (OR 2.94, 95% CI 0.12 to 73.95; 94 women). The synthesis of all studies provided very low-certainty evidence about the effect of intrauterine PRP compared with placebo or no intervention on clinical pregnancy (OR 2.22, 95% CI 1.50 to 3.27; I² = 24%; 9 studies, 824 women), multiple pregnancy (OR 2.68, 95% CI 0.81 to 8.88; I² = 0%; 2 studies, 240 women), and ectopic pregnancy (OR 2.94, 95% CI 0.12 to 73.95; 1 study, 94 women; very low-certainty evidence). Intrauterine infusion of PRP may increase the risk of preterm delivery compared with no intervention (OR 8.02, 95% CI 1.72 to 37.33; 1 study, 120 women; low-certainty evidence). No studies reported pain, infection, allergic reaction, fetal growth restriction, or fetal abnormality. Intrauterine infusion of platelet-rich plasma versus intrauterine infusion of granulocyte colony-stimulating factor Two RCTs evaluated intrauterine PRP versus intrauterine granulocyte colony-stimulating factor (G-CSF); both included women with thin endometrium, and neither was judged at low risk of bias for any outcome. We are uncertain about the effect of intrauterine PRP compared with intrauterine G-CSF on live birth (OR 0.88, 95% CI 0.43 to 1.81; 1 study, 132 women; very low-certainty evidence), miscarriage (OR 1.94, 95% CI 0.63 to 5.96; 1 study, 132 women; very low-certainty evidence), and clinical pregnancy (OR 1.24, 95% CI 0.66 to 2.35; 2 studies, 172 women; very low-certainty evidence). Neither study reported adverse outcomes other than miscarriage. Intraovarian injection of platelet-rich plasma versus no intervention One RCT evaluated PRP injection into both ovaries versus no intervention; it was judged at high risk of bias for the two outcomes it reported. We are uncertain about the effect of intraovarian PRP injection compared with no intervention on ongoing pregnancy (OR 1.09, 95% CI 0.33 to 3.63; 73 women; very low-certainty evidence) and clinical pregnancy (OR 0.90, 95% CI 0.31 to 2.60; 73 women; very low-certainty evidence). The study examined no safety outcomes. AUTHORS' CONCLUSIONS: We are uncertain about the effect of intrauterine or intraovarian administration of PRP on outcomes of assisted reproduction technology in infertile women. The pooled results should be interpreted with caution. Only one of the 12 included studies was judged at low risk of bias. Other limitations of the included trials were failure to report live birth, poor reporting of methods, lack of prospective protocol registration, low precision due to the small number of enrolled participants, indirectness due to the specific subpopulations and settings studied, and insufficient or absent safety data.

Successful equine in vitro embryo production by ICSI - effect of season, mares' age, breed, and phase of the estrous cycle on embryo production.

This retrospective study aimed at identifying factors that contribute to the success of equine in vitro embryo production by intracytoplasmic sperm injection (ICSI). A total of 7993 ovum pick-up (OPU) sessions were performed, totaling 2540 donor mares and semen from 396 stallions. Oocytes were aspirated at multiple sites in Brazil and were sent to the laboratory, within 6 h from OPU, in pre-maturation medium where they were in vitro matured (IVM) followed by ICSI and in vitro embryo culture for 7-8 days. The number of recovered oocytes, matured oocytes, cleaved embryos and blastocysts were used to explore the effect of age and breed of the donor mare, time of year in which the mare was aspirated and phase of the estrous cycle on the day of follicular aspiration. Mares between 6 and 15 years old were superior to other age groups in most parameters evaluated, including the average number of blastocysts per OPU. The impact of age was similar when evaluated within two breeds, American Quarter Horse (AQHA) and Warmblood mares. We observed that breed (AQHA, Warmblood, Crioulo, Lusitano and Mangalarga) had an important effect on most of the parameter evaluated, including number of oocytes recovered, blastocysts produced per OPU, and blastocyst rates. The overall impact of season was less pronounced than age and breed, with the only statistically significant difference being a higher rate of oocyte maturation during the summer season. Finally, most of the parameters evaluated were superior in follicular phase mares, with or without dominant follicle than luteal phase mares. In conclusion, this retrospective study revealed that breed, age, season and stage of estrous at the time of OPU are all important parameters for the success of equine embryo production by ICSI. This technology enables producing embryos all-year-round from mares of different breeds and ages from OPU-derived oocytes collected at multiple sites.

Treatment of mares with the non-steroidal anti-inflammatory drug (NSAID) phenylbutazone transiently affects in vitro maturation of equine oocytes and blastocyst development after Intracytoplasmic Sperm Injection (ICSI).

Mares enrolled in assisted reproductive technologies (ARTs) programs are often treated with non-steroidal anti-inflammatory drugs (NSAIDs), particularly phenylbutazone (Bute), due to chronic lameness. The current study was performed to determine the effect of Bute administration on the developmental competence of in vitro-matured equine oocytes subjected to Intracytoplasmic Sperm Injection (ICSI). In a Preliminary Study, immature cumulus-oocyte complexes (COCs) recovered by post-mortem ovary harvested from two healthy mares (n = 2) treated for 10 days with Bute (4.4 mg/kg, PO, BID), and four non-treated healthy mares (n = 4), were matured in vitro and subjected to Piezo-driven ICSI. Lower oocyte in vitro maturation [Bute: 25% (3/12) vs. Control: 61% (28/46)] and blastocyst rates [Bute: 0% (0/12) vs. Control: 18% (5/28)] were observed in the Bute-treated when compared to the Control mares (P < 0.05). In the Main Experiment, a group of healthy mares (n = 9) received a daily dose of Bute (4.4 mg/kg, orally, SID) for 10 days. A control group of mares (n = 10) was treated with an equal volume of placebo. Mares in both groups were subjected to ultrasound-guided transvaginal oocyte aspiration (TVA) on days 3, 33, and 77 following the last dose of Bute (PT). Recovered COCs from both mare groups were matured in vitro and subjected to Piezo-driven ICSI. By day-3 PT, oocyte in vitro maturation rate was similar between mare groups [Bute: 65% (36/55) vs. Control: 67% (78/116); P > 0.05], while oocyte recovery [Bute: 53% (55/103) vs. Control: 70% (116/166)], cleavage [Bute: 31% (11/36) vs. Control: 62% (48/78)] and blastocyst rates [Bute: [0%] (0/36) vs. Control: 28% (22/78)] were significantly different (P < 0.05). By day 33 PT and 77 PT, differences on oocyte recovery, in vitro maturation, cleavage, and blastocyst rates were not observed between mare groups. In summary, the administration of Bute for 10 consecutive days (4.4 mg/kg, PO, SID, or BID) is associated with a decrease in the ability of immature equine oocytes to undergo in vitro-maturation (Preliminary Study) and develop to the blastocyst stage following ICSI (Preliminary Study and Main Experiment). This negative effect appeared to be transient, as 30- and 77-days post-treatment, no differences on in vitro maturation, cleavage or blastocyst rates were observed.

Automated Single-Sperm Selection Software (SiD) during ICSI: A Prospective Sibling Oocyte Evaluation.

The computer-assisted program SiD was developed to assess and select sperm in real time based on motility characteristics. To date, there are limited studies examining the correlation between AI-assisted sperm selection and ICSI outcomes. To address this limit, a total of 646 sibling MII oocytes were randomly divided into two groups as follows: the ICSI group (n = 320): ICSI performed with sperm selected by the embryologist and the ICSI-SiD group (n = 326): ICSI performed with sperm selected using SiD software. Our results show a non-significant trend towards improved outcomes in the ICSI-SiD group across various biological parameters, including fertilization, cleavage, day 3 embryo development, blastocyst development, and quality on day 5. Similarly, we observed a non-significant increase in these outcomes when comparing both groups with sperm selection performed by a junior embryologist. Embryo development was monitored using a timelapse system. Some fertilization events happen significantly earlier when SiD is used for ICSI, but no significant difference was observed in the ICSI-SiD group for other timepoints. We observed comparable cumulative early and clinical pregnancy rates after ICSI-SiD. This preliminary investigation illustrated that employing the automated sperm selection software SiD leads to comparable biological outcomes, suggesting its efficacy in sperm selection.

Sex ratio shift after frozen single blastocyst transfer in relation to blastocyst morphology parameters.

The sex ratio shift was observed in peoples who underwent ART treatment. Moreover, there is limited evidence on differences in sex ratio between single frozen-thawed blastocyst morphology, insemination type and transfer days. So further research is needed in this area with regard to factors possibly affecting the sex ratio. Retrospective study based on multicenter including two large assisted reproduction centers in Shanghai and Wuhan in China. A total of 6361 singleton delivery offspring after frozen-thawed blastocyst transfer. Propensity score weighting and logistic regression models were used to estimate the associations between blastocyst morphology grading and child sex ratio. The main outcome measures is singleton sex ratio. In our study, the primary outcome measure was sex ratio which was calculated as the proportion of male newborns among all live births. Higher quality blastocysts resulted in a higher sex ratio than single poor-quality frozen-thawed blastocyst transfer. Among the three blastocyst morphological parameters of trophectoderm (TE), Grade A and B were significantly associated with a higher sex ratio than Grade C. The similar trend was observed in both IVF and ICSI treated subgroups. As compared with expansion (4 + 3), expansion degree 6 achieved a higher sex ratio in overall populations and IVF treated subgroup. Transferring blastocysts of day 6 had the highest sex ratio both in IVF group and ICSI group. A 6.95% higher sex ratio in transferring blastocysts of day 5 in IVF group than those in ICSI group. No significant association between inner cell mass degree and sex ratio was observed. However, as compared with IVF treatment, all morphology parameters achieved the similar or the biased sex ratio favoring female in ICSI treated subgroup. Quality of blastocysts was positively associated with sex ratio. TE score and expansion degree rather than ICM were significantly associated with sex ratio at birth. ICSI treatment promotes the biased sex ratio favoring female.

Elevated sperm DNA fragmentation is correlated with an increased chromosomal aneuploidy rate of miscarried conceptus in women of advanced age undergoing fresh embryo transfer cycle.

Background: Male sperm DNA fragmentation (SDF) may be associated with assisted reproductive technology (ART) outcomes, but the impact of SDF on the occurrence of aneuploid-related miscarriage remains controversial. Methods: Genome-wide single-nucleotide polymorphism-based chromosomal microarray analysis was performed on 495 miscarried chorionic villus samples undergone IVF/ICSI treatment from the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University. SDF was assessed using sperm chromatin structure assay. Patients were divided into four groups according to embryo transfer cycle type and maternal age, and the correlation between SDF and chromosome aberration was analyzed. A receiver operating characteristic (ROC) curve was utilized to find the optimal threshold. Results: Total chromosomal aneuploidy rate was 54.95%, and trisomy was the most common abnormality (71.32%). The chromosomally abnormal group had higher SDF than the normal group (11.42% [6.82%, 16.54%] vs. 12.95% [9.61%, 20.58%], P = 0.032). After grouping, elevated SDF was significantly correlated with an increasing chromosome aneuploidy rate only in women of advanced age who underwent fresh embryo transfer (adjusted odds ratio:1.14 [1.00-1.29], adjusted-P = 0.045). The receiver operating characteristic curve showed that SDF can predict the occurrence of chromosomal abnormality of miscarried conceptus in this group ((area under the curve = 0.76 [0.60-0.91], P = 0.005), and 8.5% was the optimum threshold. When SDF was ≥ 8.5%, the risk of such patients increased by 5.76 times (adjusted odds ratio: 6.76 [1.20-37.99], adjusted-P = 0.030). Conclusion: For women of advanced maternal age undergoing fresh embryo transfer, older oocytes fertilized using sperm with high SDF in IVF/ICSI treatment might increase the risk of chromosomal abnormality in miscarried conceptus.

Diverse impacts of female chromosomal polymorphisms on assisted reproduction outcomes: a retrospective cohort study.

BACKGROUND: The effects of female chromosomal polymorphisms (FCPs) on various aspects of reproductive health have been investigated, yet the findings are frequently inconsistent. This study aims to clarify the role of FCPs on the outcomes of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). METHODS: This retrospective cohort study comprised 951 couples with FCPs and 10,788 couples with normal karyotypes who underwent IVF/ICSI treatment at Peking University Third Hospital between 2015 and 2021. The exposure was FCPs. The embryological outcomes and clinical outcomes were compared. RESULTS: The FCPs, as a whole, compromised the oocyte maturation rate (76.0% vs. 78.8%, P = 0.008), while they did not adversely affect other IVF/ICSI outcomes. Further detailed analyses showed that every type of FCPs contributed to the lower oocyte maturation rate, particularly the rare FCPs (69.0% vs. 78.8%, P = 0.008). The female qh + was associated with a higher normal fertilization rate (63.0% vs. 59.2%, adjusted P = 0.022), a higher clinical pregnancy rate (37.0% vs. 30.7%, adjusted P = 0.048), and a higher live birth rate (27.0% vs.19.0%, adjusted P = 0.003) in couples undergoing IVF. Conversely, in couples undergoing ICSI, female qh + was found to be related to a lower normal fertilization rate (58.8% vs. 63.8%, P = 0.032), a comparable clinical pregnancy rate (25.7% vs. 30.9%, P = 0.289), and a comparable live birth rate (19.8% vs. 19.2%, P = 0.880) compared to the control group. Additionally, an increased risk of preterm birth was observed in women undergoing IVF with multiple polymorphisms (62.5% vs. 16.9%, adjusted P <  0.001) and in women undergoing ICSI with pstk+ (36.4% vs. 15.4%, P = 0.036). CONCLUSIONS: Our research unravels the diverse impacts of various FCPs on IVF/ICSI outcomes, highlighting the detrimental effects of FCPs on oocyte maturation and the risk of preterm birth.

Assisted reproduction and congenital malformations: A systematic review and meta-analysis.

Prior studies have explored the links between congenital anomalies and assisted reproduction techniques, among other factors. However, it remains unclear whether a particular technique harbors an inherent risk of major congenital anomalies, either cumulatively or in an organ-specific manner. A meta-analysis was conducted using relevant studies from inception to February 2023 using six databases and two appropriate registers. Sources of heterogeneity were explored using sub-group analysis, using study weight, risk of bias and geographical location of original studies. Neonates conceived through assisted reproduction appear to have a higher risk of major congenital anomalies compared to naturally conceived neonates, OR 0.67 [95% CI 0.59, 0.76], I2 = 97%, p < 0.00001, with neonates conceived through intracytoplasmic sperm injection (ICSI) at a 9% higher chance of being affected in comparison to neonates conceived through in vitro fertilization (IVF). The increase in cardiac, gastrointestinal (GI), and neurological congenital anomalies appears to be independent of the assisted reproduction technique, while urogenital and musculoskeletal (MSK) anomalies were found to be increased in ICSI compared with IVF, OR 0.83 [95% CI 0.69, 0.98]; p = 0.03, I2 = 0%, and OR 0.65 [95% CI 0.49, 0.85]; p = 0.002, I2 = 80%, respectively. Neonates conceived using assisted reproduction techniques appear to be at higher risk of major congenital anomalies, with a higher risk attributable to conception using ICSI. The increase in cardiac, neurological, and GI congenital anomalies does not appear to be technique-specific, while the opposite held true for urogenital and MSK anomalies.

Embryology with precision: effective quality control in the in vitro fertilization laboratory.

The purpose of this review is to address the critical need for standardization and clarity in the use of key performance indicators (KPIs) within the realm of in vitro fertilization (IVF), particularly emphasizing the integration of preimplantation genetic testing (PGT) processes. This review is timely and relevant given the persistently modest success rates of IVF treatments, which stand at approximately 30%, and the growing complexity of IVF procedures, including PGT practices. The review synthesizes recent findings across studies focusing on technical and clinical KPIs in embryology and genetic laboratories, identifying gaps in current research and practice, particularly the lack of standardized KPIs and terminology. Recent findings highlighted include the critical evaluation of technical KPIs such as Intracytoplasmic Sperm Injection (ICSI) fertilization rates, embryo development rates, and laboratory performance metrics, alongside clinical KPIs like the proportion of mature oocytes and clinical pregnancy rates. Notably, the review uncovers a significant gap in integrating and standardizing KPIs for PGT applications, which is essential for improving IVF outcomes and genetic diagnostic accuracy. The implications of these findings are profound for both clinical practice and research. For clinical practice, establishing a standardized set of KPIs, especially for PGT, could significantly enhance the success rates of IVF treatments by providing clearer benchmarks for quality and performance. For research, this review underscores the necessity for further studies to close the identified gaps, promoting a more integrated and standardized approach to KPIs in IVF and PGT processes. This comprehensive approach will not only aid in improving clinical outcomes but also in advancing the field of reproductive medicine.

Live birth derived from a markedly large polar body oocyte: a rare case report.

Oocytes with excessively large first polar bodies (PB1) often occur in assisted reproductive procedures. Many times these oocytes are discarded without insemination and, as a result, the application of this portion of oocytes has scarcely been reported to date. Few studies have examined large PB1 oocytes in infertile women and have virtually entirely studied genetic variations for large PB1 oocyte abnormalities. Here, we describe an unusual case of a live birth from a remarkably large PB1 oocyte in a frozen embryo transfer (FET) cycle. This is the first instance of a successful live birth resulting from a PB1 oocyte with an extremely large polar body measuring 80 µM × 40 µM in size. The large PB1 oocyte was performed by an early rescue intracytoplasmic sperm injection (r-ICSI) and was formed into a blastocyst on day 5. Following FET, a healthy boy baby weighing 3100 g was finally delivered by caesarean section at 37 weeks and 5 days after conception. Additionally, there were no complications throughout the antenatal period or the perinatal phase of this following full-term delivery. In this study, it is revealed for the first time that a huge PB1 oocyte can be fertilized, resulting in the growth of a blastocyst, a subsequent pregnancy, and a live birth. This new information prompts us to reconsider the use of large PB1 oocytes. More insightful talks should be given attention to prevent the waste of embryos because not all oocytes with aberrant morphology are unavailable.

Safety evaluation of single-sperm cryopreservation technique applied in intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety.

Impact of thyroid autoimmunity on the cumulative live birth rates after IVF/ICSI treatment cycles.

BACKGROUND: Cumulative live birth rate (CLBR) is considered as the most important endpoint for assessing the probability of having a baby in a complete in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment cycle. Many previous studies have focused on the association between thyroid autoimmunity (TAI) and live birth rate after first embryo transfer cycle, however, evidence on whether the presence of TAI affects the CLBR is lacking. The purpose of this study is to investigate the impact of TAI on the CLBR in a complete IVF/ICSI cycle. METHODS: This retrospective study included 12,796 women who underwent their first IVF/ICSI treatment between January 2019 and February 2021. Based on the levels of thyroid antibodies, 2,603 women were assigned to the TAI group, and 10,193 women were assigned to the control group. Subgroup analysis was performed according to the different causes of infertility (including male factor only, ovulation disorder, tubal factor, endometriosis and unexplained infertility) and different types and titres of thyroid antibodies. The primary outcome in this study was CLBR, which included live births from the fresh embryo transfer cycle and all subsequent frozen-thawed embryo transfer cycles performed before December 2021. RESULTS: There was no significant difference in the CLBR between the TAI and control groups, even after adjusting for relevant confounders including age, body mass index, cause of infertility, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live birth: 50.6% vs. 52.1%, OR 0.94, 95% CI 0.86-1.02, adjusted OR 0.97, 95%CI 0.89-1.06). Subgroup analysis showed that no significant difference was observed in CLBR between the TAI and control groups for all causes of infertility, except for infertility attributed to endometriosis. Among women with endometriosis, the CLBR was significantly lower in the TAI group than that in the control group; however, this difference was not significant after adjusting for potential confounders including age, body mass index, thyroid function, protocols of controlled ovarian stimulation, type of transfer (fresh vs. frozen), type of transferred embryo (cleavage-stage embryo vs. blastocyst), and fertilization method (IVF vs. ICSI) (cumulative live births: 43.1% vs. 51.0%, OR 0.73, 95% CI 0.53-0.99, adjusted OR 0.74, 95% CI 0.53-1.02). Another subgroup analysis demonstrated that the type and titre of thyroid antibody did not affect CLBR in women with TAI. CONCLUSIONS: In our study, there was no significant difference in the CLBR between women with TAI and those without TAI, which suggests that TAI did not affect the chances of having a baby in a complete IVF/ICSI treatment cycle.

Comparison of pregnancy outcomes in women with normal ovarian response to the gonadotropin-releasing hormone agonist protocol using different trigger methods: a single-center retrospective cohort study based on propensity score matching.

PURPOSE: To investigate whether gonadotropin-releasing hormone agonist (GnRH-a) combined with human chorionic gonadotropin (HCG) can improve pregnancy outcomes in patients with normal ovarian response (NOR). METHODS: In this retrospective cohort study, data of 404 NOR patients undergoing fresh embryo transfer (ET) from 2018 to 2022 were studied. Patients were divided into HCG group and HCG plus GnRH-a group according to trigger methods. After confounding factors were controlled by propensity score matching, 67 cases were included in HCG group and HCG plus GnRH-a group, respectively, and pregnancy outcomes were assessed. Basal data, ovarian stimulation, embryological data and pregnancy outcomes were compared. The effect of trigger methods on pregnancy outcomes was analyzed by binary logistic regression. RESULTS: There was no statistically significant differences in embryological data, embryo implantation rate, clinical pregnancy rate, live birth rate of ET, number of fresh embryos transferred and total number of embryos transferred after one cycle of oocyte retrieval. While, cumulative live birth rate (CLBR) was better in the dual-trigger group than in the HCG group. The binary logistic regression analysis indicated that the trigger methods had an independent influence on embryo implantation and cumulative live birth. CONCLUSIONS: During IVF/ICSI, dual-trigger could potentially play a role in improving oocyte quality, ensuring embryo implantation rate, clinical pregnancy rate, live birth rate of ET and cumulative live birth rate at the end of one ovum pick-up (OPU) cycle, and reducing the physical, temporal and financial negative consequences due to repeated OPU cycle.

Ovarian response and embryo ploidy following oral micronized progesterone-primed ovarian stimulation versus GnRH antagonist protocol. A prospective study with repeated ovarian stimulation cycles.

STUDY QUESTION: Is there any difference in ovarian response and embryo ploidy following progesterone-primed ovarian stimulation (PPOS) using micronized progesterone or GnRH antagonist protocol? SUMMARY ANSWER: Pituitary downregulation with micronized progesterone as PPOS results in higher number of oocytes retrieved and a comparable number of euploid blastocysts to a GnRH antagonist protocol. WHAT IS KNOWN ALREADY: Although the GnRH antagonist is considered by most the gold standard protocol for controlling the LH surge during ovarian stimulation (OS) for IVF/ICSI, PPOS protocols are being increasingly used in freeze-all protocols. Still, despite the promising results of PPOS protocols, an early randomized trial reported potentially lower live births in recipients of oocytes resulting following downregulation with medroxyprogesterone acetate as compared with a GnRH antagonist protocol. The scope of the current prospective study was to investigate whether PPOS with micronized progesterone results in an equivalent yield of euploid blastocysts to a GnRH antagonist protocol. STUDY DESIGN, SIZE, DURATION: In this prospective study, performed between September 2019 to January 2022, 44 women underwent two consecutive OS protocols within a period of 6 months in a GnRH antagonist protocol or in a PPOS protocol with oral micronized progesterone. PARTICIPANTS/MATERIALS, SETTING, METHODS: Overall, 44 women underwent two OS cycles with an identical fixed dose of rFSH (225 or 300 IU) in both cycles. Downregulation in the first cycles was performed with the use of a flexible GnRH antagonist protocol (0.25 mg per day as soon as one follicle of 14 mm) and consecutively, after a washout period of 1 month, control of LH surge was performed with 200 mg of oral micronized progesterone from stimulation Day 1. After the completion of both cycles, all generated blastocysts underwent genetic analysis for aneuploidy screening (preimplantation genetic testing for aneuplody, PGT-A). MAIN RESULTS AND THE ROLE OF CHANCE: Comparisons between protocols did not reveal differences between the duration of OS. The hormonal profile on the day of trigger revealed statistically significant differences between protocols in all the tested hormones except for FSH: with significantly higher serum E2 levels, more elevated LH levels and higher progesterone levels in PPOS cycles as compared with antagonist cycles, respectively. Compared with the GnRH antagonist protocol, the PPOS protocol resulted in a significantly higher number of oocytes (12.7 ± 8.09 versus 10.3 ± 5.84; difference between means [DBM] -2.4 [95% CI -4.1 to -0.73]), metaphase II (9.1 ± 6.12 versus 7.3 ± 4.15; DBM -1.8 [95% CI -3.1 to -0.43]), and 2 pronuclei (7.1 ± 4.99 versus 5.7 ± 3.35; DBM -1.5 [95% CI -2.6.1 to -0.32]), respectively. Nevertheless, no differences were observed regarding the mean number of blastocysts between the PPOS and GnRH antagonist protocols (2.9 ± 2.11 versus 2.8 ± 2.12; DBM -0.07 [95% CI -0.67 to 0.53]) and the mean number of biopsied blastocysts (2.9 ± 2.16 versus 2.9 ± 2.15; DBM -0.07 [95% CI -0.70 to 0.56]), respectively. Concerning the euploidy rates per biopsied embryo, a 29% [95% CI 21.8-38.1%] and a 35% [95% CI 26.6-43.9%] were noticed in the PPOS and antagonist groups, respectively. Finally, no difference was observed for the primary outcome, with a mean number of euploid embryos of 0.86 ± 0.90 versus 1.00 ± 1.12 for the comparison of PPOS versus GnRh antagonist. LIMITATIONS, REASONS FOR CAUTION: The study was powered to detect differences in the mean number of euploid embryos and not in terms of pregnancy outcomes. Additionally, per protocol, there was no randomization, the first cycle was always a GnRH antagonist cycle and the second a PPOS with 1 month of washout period in between. WIDER IMPLICATIONS OF THE FINDINGS: In case of a freeze-all protocol, clinicians may safely consider oral micronized progesterone to control the LH surge and patients could benefit from the advantages of a medication of oral administration, with a potentially higher number of oocytes retrieved at a lower cost, without any compromise in embryo ploidy rates. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by an unrestricted grant from Theramex. N.P.P. has received Research grants from Merck Serono, Organon, Ferring Pharmaceutical, Roche, Theramex, IBSA, Gedeon Richter, and Besins Healthcare; honoraria for lectures from: Merck Serono, Organon, Ferring Pharmaceuticals, Besins International, Roche Diagnostics, IBSA, Theramex, and Gedeon Richter; consulting fees from Merck Serono, Organon, Besins Healthcare, and IBSA. M.d.M.V., F.M., and I.R. declared no conflicts of interest. TRIAL REGISTRATION NUMBER: The study was registered at Clinical Trials Gov. (NCT04108039).