Intracytoplasmic sperm injection induces transgenerational abnormalities in mice.

In vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are 2 major assisted reproductive techniques (ARTs) used widely to treat infertility. Recently, spermatogonial transplantation emerged as a new ART to restore fertility to young patients with cancer after cancer therapy. To examine the influence of germ cell manipulation on behavior of offspring, we produced F1 offspring by a combination of two ARTs, spermatogonial transplantation and ICSI. When these animals were compared with F1 offspring produced by ICSI using fresh wild-type sperm, not only spermatogonial transplantation-ICSI mice but also ICSI-only control mice exhibited behavioral abnormalities, which persisted in the F2 generation. Furthermore, although these F1 offspring appeared normal, F2 offspring produced by IVF using F1 sperm and wild-type oocytes showed various types of congenital abnormalities, including anophthalmia, hydrocephalus, and missing limbs. Therefore, ARTs can induce morphological and functional defects in mice, some of which become evident only after germline transmission.

Results and perinatal outcomes from 189 ICSI cycles of couples with asthenozoospermic men and flagellar defects assessed by transmission electron microscopy.

RESEARCH QUESTION: Do patients presenting with flagella ultrastructural defects as assessed by electron microscopy, and defined within three phenotypes (dysplasia of the fibrous sheath [DFS], primary flagellar dyskinesia [PFD] and non-specific flagellar abnormalities [NSFA]), have decreased chances of success in intracytoplasmic sperm injection (ICSI) or adverse obstetric and neonatal outcomes? DESIGN: Retrospective analysis of 189 ICSI cycles from 80 men with spermatozoa flagellum ultrastructural defects (DFS [n = 16]; PFD [n = 14]; NSFA [n = 50] compared with a control group (n = 97). Cycles were cumulatively analysed. All fresh and frozen embryo transfers resulting from each ICSI attempt were included. The effect of transmission electron microscopy (TEM) phenotype on the main ICSI outcomes was assessed by a multivariate logistic regression combined with a generalized linear mixed model to account for the non-independence of the observations. RESULTS: No predictive value of TEM phenotype was found on the main outcomes of ICSI, namely fertilization rates, pregnancy and delivery rates, and cumulative pregnancy and delivery rates. Cumulative pregnancy rates ranged from 29.0-43.3% in the different TEM phenotype subgroups compared with 36.8% in the control group. Cumulative live birth rates ranged from 24.6-36.7% compared with 31.4% in the control group. No increase was found in miscarriages, preterm births, low birth weights or birth abnormalities. CONCLUSIONS: Data on the cumulative chances of success in ICSI of patients with ultrastructural flagellar defects, a rare cause of male infertility often associated with an underlying genetic cause, are reassuring, as are obstetrical and neonatal outcomes in this population.

Singleton pregnancy using in vitro fertilization or intracytoplasmic sperm injection does not increase risk of bleeding in cesarean delivery: a retrospective cohort study.

PURPOSE: Several studies indicate that assisted reproductive technology (ART) including in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) pregnancies carries increased risk of complications including postpartum hemorrhage (PPH). However, the association between IVF/ICSI and the bleeding risk particularly in cesarean delivery has not been systematically assessed. The aim of this study was to evaluate bleeding risk during and after cesarean delivery in parturients who conceived using IVF or ICSI. METHODS: This is a retrospective observational study analyzing data from 310 parturients who underwent cesarean delivery: 155 who had conceived using IVF or ICSI (IVF/ICSI group) and 155 age and year of delivery matched controls who had conceived spontaneously (control group). The primary outcome measure was the amount of blood lost during and within 24 h after cesarean delivery. Secondary outcome measure was the incidence of severe PPH. With 132 parturients in each group, we had 90% power to detect a 200 mL difference in the bleeding amount, at a 0.05 two-sided significance level. RESULTS: The amount of bleeding in the IVF/ICSI group was 1234 ± 669 mL, which was 124 mL (11.2%) greater than that in the control group (95% CI - 34 to 282; p = 0.12). The incidence of severe PPH in the IVF/ICSI group and in the control group was 23.9% and 16.8%, respectively (p = 0.16), and the unadjusted odds ratio was 1.6 (95% CI, 0.9-2.7; p = 0.12). No significant independent effect of IVF/ICSI on the bleeding amount and the incidence of severe PPH was observed in multivariable regression analyses (p = 0.22, p = 0.16). CONCLUSION: In this study, IVF and ICSI were not associated with increasing risk of bleeding in cesarean delivery.

Maternal preconception thyroid autoimmunity is associated with neonatal birth weight conceived by PCOS women undergoing their first in vitro fertilization/intracytoplasmic sperm injection.

BACKGROUND: Thyroid autoimmunity and polycystic ovary syndrome (PCOS) are the most common endocrinopathies and have close relationships based on common etiology and pathogenesis, including genetic susceptibility, metabolic disorders, hormonal dysregulation, immune response, and inflammatory activation. The co-occurrence of both diseases is associated with adverse reproductive outcomes, but its effect on neonatal outcomes remains largely unknown. We aim to explore the effect of thyroid autoimmunity on neonatal birth weight in PCOS women undergoing IVF/ICSI. METHODS: This is a retrospective analysis of 486 PCOS women who underwent the first IVF/ICSI cycles and gave birth to 361 singletons and 125 twins during 2018 - 2020 at a reproductive center. The associations between maternal preconception serum thyroid function and autoimmunity indicators and birth weights of the singleton and twin groups were evaluated using generalized linear models (GLMs) and generalized estimate equations (GEEs), respectively. Analyses were further stratified by neonatal sex, maternal age, and maternal preconception BMI to assess the possible interaction effects. RESULTS: Maternal preconception serum TPOAb had a significant negative association with singleton birth weight (P for trends = 0.03). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in singleton birth weight of - 119.72 g (95% CI: - 222.68 g, - 16.70 g). Maternal preconception serum TPOAb had a significant positive association with twin birth weight (P for trends = 0.01). Compared with women in the first tertile of TPOAb, women in the third tertile had a change in twin birth weight of 138.62 g (95% CI: 33.96 g, 243.30 g). Besides, maternal preconception serum TPOAb had a specific association with increased twin birth weight for female neonates, a specific association with decreased singleton birth weight for PCOS women under 35 years, and a specific association with decreased twin birth weight for overweight PCOS women (all P for interactions < 0.05). CONCLUSIONS: Maternal preconception thyroid autoimmunity may affect the birth weights of both singleton and twin neonates. Further large cohorts and experimental studies are required to confirm these findings and explore the underlying mechanisms.

An atypical erectile dysfunction patient with infertility treated with penile prosthesis implantation and testicular epididymal sperm aspiration (TESA)-intracytoplasmic sperm injection (ICSI): A case report.

RATIONALE: Erectile dysfunction (ED) is common in middle-aged and elderly men, affecting more than 100 million males worldwide. Most ED cases can be attributed to organic and/or psychological factors. Here we report an atypical ED case with no clear manifestation fitting the diagnosis for recognized types of ED. PATIENT CONCERNS: The 35-year-old male is unable to have normal erection since puberty, and unable to complete intercourse with his wife. He had no history of trauma, surgery or psychiatric/psychological disease. The patient has a normal male karyotype. There is no significant finding in physical examination, nocturnal penile tumescence test, and ultrasound measurement of penis vascular functions. The serum levels of major hormones are all in normal ranges. DIAGNOSES: Atypical ED, psychogenic ED not excluded; infertility. INTERVENTIONS: Oral phosphodiesterase inhibitors Tadalafil (20 mg, BIW) or Sildenafil (50 mg, BIW) had no effect in this patient. Penile prosthesis implantation helped the patient to acquire normal sexual life, but did solve the ejaculation failure and infertility. Motile sperms were obtained by testicular epididymal sperm aspiration under the guidance of ultrasound, and intracytoplasmic sperm injection was performed with occytes retrieved from his wife. OUTCOMES: The patient sexual life was significantly improved after penile prosthesis implantation; the patient wife is currently in the first trimester of pregnancy as the result of in vitro fertilization. CONCLUSIONS: The no response to phosphodiesterase type 5 inhibitors (PDE5) treatment may suggest an impediment of PDE5-related pharmacological pathways or the presence of defect/injury in the neural system. This special case raises a question if some patients with persistent ED may have similar manifestations and can be treated with the same procedures.

Nomogram for predicting the risk of preterm delivery after IVF/ICSI treatment: an analysis of 11513 singleton births.

Background: There is a higher risk of preterm delivery (PTD) in singleton live births conceived after in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) compared with spontaneously conceived pregnancies. The objective of our study was to build a predictive nomogram model to suggest the possibility of PTD in singleton pregnancies after IVF/ICSI treatment. Method: 11513 IVF/ICSI cycles with singleton live births were enrolled retrospectively. These cycles were randomly allocated into a training group (80%) and a validation group (20%). We used the multivariate logistics regression analysis to determine prognostic factors for PTD in the training group. A nomogram based on the above factors was further established for predicting PTD. Receiver operating characteristic curves (ROC), areas under the ROC curves (AUC), concordance index (C-index), and calibration plots were analyzed for assessing the performance of this nomogram in the training and validation group. Results: There were fourteen risk factors significantly related to PTD in IVF/ICSI singleton live births, including maternal body mass index (BMI) > 24 kg/m2, smoking, uterine factors, cervical factors, ovulatory factors, double embryo transferred (DET), blastocyst transfer, FET, vanishing twin syndrome (VTS), obstetric complications (placenta previa, placenta abruption, hypertensive of pregnancies, and premature rupture of membrane), and a male fetus. These factors were further incorporated to construct a nomogram prediction model. The AUC, C-index, and calibration curves indicated that this nomogram exhibited fair performance and good calibration. Conclusions: We found that the occurrence of PTD increased when women with obesity, smoking, uterine factors, cervical factors, ovulatory factors, DET, VTS, and obstetric complications, and a male fetus. Furthermore, a nomogram was constructed based on the above factors and it might have great value for clinic use.

Compared with conventional insemination, intracytoplasmic sperm injection provides no benefit in cases of nonmale factor infertility as evidenced by comparable euploidy rate.

OBJECTIVE: To evaluate whether differences in euploidy rates exist between intracytoplasmic sperm injection (ICSI) and conventional insemination (CI) in nonmale factor infertility cases. DESIGN: Retrospective cohort study. SETTING: A single, academically affiliated infertility center in the United States. PATIENTS: A total of 3554 patients who underwent in vitro fertilization cycles from January 2014 to December 2021. All cycles that had preimplantation testing for aneuploidy (PGT-A) performed by trophectoderm biopsy and had a postpreparation sperm concentration >4 million total motile sperm per milliliter were included. MAIN OUTCOME MEASURES: The primary outcome was the embryo euploidy rate per embryo biopsied in the ICSI vs. CI group. Secondary outcomes included the fertilization rate and number of embryos biopsied. Generalized estimating equations with a Poisson distribution were used to estimate the euploid rate ratio (with total embryos biopsied as an offset), while accounting for multiple retrievals per patient. To adjust for confounding, a propensity score model was fit for ICSI using 14 baseline female and male characteristics. RESULTS: Oocytes retrieved and the number of embryos biopsied were similar in both groups, while the fertilization rate per oocyte retrieved was significantly lower with ICSI (0.64 vs. 0.66). The proportion of euploid embryos in the ICSI group was significantly lower when compared with CI (0.47 vs. 0.52), with a euploid rate ratio of 0.89. Interestingly, when accounting for the variation in PGT reference laboratories over the study time period, adjusting for the date of procedure did not change the relationship between ICSI and euploid rate (rate ratio = 0.89); however, after adjusting for the PGT reference laboratory, the relationship between ICSI and euploid rate was no longer significant (rate ratio = 0.97). CONCLUSIONS: In the setting of nonmale factor infertility, ICSI resulted in a lower fertilization rate and an 11% lower embryo euploid rate compared with CI. Although the data are not statistically significant when adjusted for the PGT reference laboratory, we still can conclude that ICSI does not provide any benefit. These data support the recommendation that CI should be the preferred methodology for fertilization in nonmale factor infertility cases.

Impact of parental chromosomal polymorphisms on the incidence of congenital anomalies and perinatal complications in a cohort of newborns conceived after ICSI + PGT-A.

BACKGROUND: To assess the association between chromosomal polymorphisms (CPM) with congenital anomalies and perinatal complications in a cohort of newborns from couples undergoing intracytoplasmic sperm injection (ICSI), trophectoderm biopsy, and preimplantation genetic testing for aneuploidy (PGT-A). METHODS: A retrospective cohort of singletons conceived after ICSI, trophectoderm biopsy, and PGT-A cycles performed at IVIRMA clinics in Spain over 4 years was involved in the study. Newborns were classified according to the parental karyotype analysis: Group I: non-carriers, Group II: CPM carriers. Couples with chromosomal anomalies and instances when both partners were CPM carriers were excluded from the study. The groups were compared for several perinatal complications. RESULTS: There was a significant decrease in the number of NB with complications in the carrier group compared to the non-carriers (19.7% vs 31.9%, p = 0.0406). There were no statistical differences among the two groups regarding congenital anomalies, preterm birth, alterations in birth length and weight, cranial perimeter, Apgar test score, or sex ratio (p > 0.05). CONCLUSIONS: Chromosomal polymorphisms appear to have no adverse effects on congenital anomalies or perinatal complications on newborns from ICSI + PGT-A cycles.

Associations between epigenetic age acceleration and infertility.

STUDY QUESTION: Is the use of ART, a proxy for infertility, associated with epigenetic age acceleration? SUMMARY ANSWER: The epigenetic age acceleration measured by Dunedin Pace of Aging methylation (DunedinPoAm) differed significantly between non-ART and ART mothers. WHAT IS KNOWN ALREADY: Among mothers who used ART, epigenetic age acceleration may be associated with low oocyte yield and poor ovarian response. However, the difference in epigenetic age acceleration between non-ART and ART mothers (or even fathers) has not been examined. STUDY DESIGN, SIZE, DURATION: The Norwegian Mother, Father and Child Cohort Study (MoBa) recruited pregnant women and their partners across Norway at around 18 gestational weeks between 1999 and 2008. Approximately 95 000 mothers, 75 000 fathers and 114 000 children were included. Peripheral blood samples were taken from mothers and fathers at ultrasound appointments or from mothers at childbirth, and umbilical cord blood samples were collected from the newborns at birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the MoBa participants, we selected 1000 couples who conceived by coitus and 894 couples who conceived by IVF (n = 525) or ICSI (n = 369). We measured their DNA methylation (DNAm) levels using the Illumina MethylationEPIC array and calculated epigenetic age acceleration. A linear mixed model was used to examine the differences in five different epigenetic age accelerations between non-ART and ART parents. MAIN RESULTS AND THE ROLE OF CHANCE: We found a significant difference in the epigenetic age acceleration calculated by DunedinPoAm between IVF and non-ART mothers (0.021 years, P-value = 2.89E-06) after adjustment for potential confounders. Further, we detected elevated DunedinPoAm in mothers with tubal factor infertility (0.030 years, P-value = 1.34E-05), ovulation factor (0.023 years, P-value = 0.0018) and unexplained infertility (0.023 years, P-value = 1.39E-04) compared with non-ART mothers. No differences in epigenetic age accelerations between non-ART and ICSI fathers were found. DunedinPoAm also showed stronger associations with smoking, education and parity than the other four epigenetic age accelerations. LIMITATIONS, REASONS FOR CAUTION: We were not able to determine the directionality of the causal pathway between the epigenetic age accelerations and infertility. Since parents' peripheral blood samples were collected after conception, we cannot rule out the possibility that the epigenetic profile of ART mothers was influenced by the ART treatment. Hence, the results should be interpreted with caution, and our results might not be generalizable to non-pregnant women. WIDER IMPLICATIONS OF THE FINDINGS: A plausible biological mechanism behind the reported association is that IVF mothers could be closer to menopause than non-ART mothers. The pace of decline of the ovarian reserve that eventually leads to menopause varies between females yet, in general, accelerates after the age of 30, and some studies show an increased risk of infertility in females with low ovarian reserve. STUDY FUNDING/COMPETING INTEREST(S): This study was partly funded by the Research Council of Norway (Women's fertility, project no. 320656) and through its Centres of Excellence Funding Scheme (project no. 262700). M.C.M. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (grant agreement number 947684). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Impact of uterine malformations on pregnancy and neonatal outcomes of IVF/ICSI-frozen embryo transfer.

STUDY QUESTION: What is the impact of uterine malformations on reproductive and neonatal outcomes of IVF/ICSI-frozen embryo transfer? SUMMARY ANSWER: Unification defective uteri are associated with poorer neonatal outcomes including higher preterm delivery rate and lower birthweight, and septate uteri are associated with worse fertility outcomes including higher miscarriage and lower live birth rates (LBRs). WHAT IS KNOWN ALREADY: Several studies have investigated the negative effects of uterine malformations on pregnancy outcomes. However, an all-round and definitive conclusion has not been reached yet owing to the relatively low incidence of the disease and the heterogeneity of study populations, especially among women undergoing ART. STUDY DESIGN, SIZE, DURATION: This was a retrospective cohort study including 411 women with congenital uterine anomalies and 14 936 women with a normal uterus who underwent first frozen-thawed embryo transfer cycles of IVF/ICSI from July 2008 to August 2019. We compared reproductive outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Reproductive outcomes of women with uterine malformations were studied through three propensity score-matched comparisons (patients with bicorporeal uterus, septate uterus and hemi-uterus [bicorporeal, septate and hemi-uterus groups, respectively] along with corresponding control groups without uterine malformations). We also compared pregnancy and neonatal outcomes, and performed subgroup analysis addressing didelphus, bicornuate uteri and septate uteri before and after surgery independently. MAIN RESULTS AND THE ROLE OF CHANCE: Compared to the matched control group, women with a bicorporeal uterus had a significantly lower LBR (24.4% versus 34.8%, odds ratio (OR) 0.61 [95% CI: 0.37, 1.00], P = 0.048). The incidence of miscarriage and preterm delivery was higher but not statistically significant (29.0% versus 18.1%, OR 1.85 [95% CI: 0.82, 4.19], P = 0.135; 22.6% versus 9.9%, OR 2.64 [95% CI: 1.07, 6.52], P = 0.063, respectively). In addition, the bicorporeal group had a significantly lower gestational age, higher caesarean rate and lower birthweight than bicorporeal control. Women with a septate uterus had comparable clinical pregnancy rates to controls (43.3% versus 49.9%, OR 0.77 [95% CI: 0.57, 1.04], P = 0.091), increased miscarriage rates (23.5% versus 13.0%, OR 2.05 [95% CI: 1.18, 3.58], P = 0.010) and lower LBRs (29.4% versus 42.2%, OR 0.57 [95% CI: 0.41, 0.79], P = 0.001). In both singleton and twins pregnancies, pregnancy and neonatal outcomes were comparable between women with a septate uterus and control. Women with a hemi-uterus had a tendency for lower clinical pregnancy rate (36.8% versus 42.3%, OR 0.80 [95% CI: 0.52, 1.21], P = 0.287) and LBR (29.8% versus 33.1%, OR 0.86 [95% CI: 0.55, 1.34], P = 0.502), compared to women without malformations. The incidences of miscarriage and preterm delivery, respectively, were 16.7% versus 16.6% (OR 1.01 [95% CI: 0.41, 2.47], P = 0.989), and 9.5% versus 11.4% (OR 0.82 [95% CI: 0.27, 2.51], P = 1) in women with a hemi-uterus as compared to control. LIMITATIONS, REASONS FOR CAUTION: This was a single-centre, retrospective study in which neonatal data were extracted from parental questionnaires. The information on uteri septum type and surgery methods was poorly presented, with limited detail. In patients with uterine malformations, the number of babies with birth defects and twin pregnancies was relatively small, limiting the power of the study. WIDER IMPLICATIONS OF THE FINDINGS: Compared to patients with a normal uterus, women with uterine malformation have poorer reproductive outcomes. Pregnant women with a uterine anomaly need to be managed as high-risk pregnancies and followed with appropriate obstetric review. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Ministry of Technology (2018YFC1003000), the Elite Team Project of Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JY201801), Shanghai Sailing Program (21YF1423200) and the Fundamental Research Program Funding of Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine (JYZZ117). B.W.M. is supported by an NHMRC Investigatorgrant (GNT1176437). B.W.M. reports consultancy (with stock options) for ObsEva. B.W.M. has received research funding from Ferring and Merck. The authors declare no other competing interests. TRIAL REGISTRATION NUMBER: N/A.

Altered Umbilical Cord Blood Nutrient Levels, Placental Cell Turnover and Transporter Expression in Human Term Pregnancies Conceived by Intracytoplasmic Sperm Injection (ICSI).

Assisted reproductive technologies (ART) may increase risk for abnormal placental development, preterm delivery and low birthweight. We investigated placental morphology, transporter expression and paired maternal/umbilical fasting blood nutrient levels in human term pregnancies conceived naturally (n = 10) or by intracytoplasmic sperm injection (ICSI; n = 11). Maternal and umbilical vein blood from singleton term (>37 weeks) C-section pregnancies were assessed for levels of free amino acids, glucose, free fatty acids (FFA), cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low-density lipoprotein (VLDL) and triglycerides. We quantified placental expression of GLUT1 (glucose), SNAT2 (amino acids), P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) (drug) transporters, and placental morphology and pathology. Following ICSI, placental SNAT2 protein expression was downregulated and umbilical cord blood levels of citrulline were increased, while FFA levels were decreased at term (p < 0.05). Placental proliferation and apoptotic rates were increased in ICSI placentae (p < 0.05). No changes in maternal blood nutrient levels, placental GLUT1, P-gp and BCRP expression, or placental histopathology were observed. In term pregnancies, ICSI impairs placental SNAT2 transporter expression and cell turnover, and alters umbilical vein levels of specific nutrients without changing placental morphology. These may represent mechanisms through which ICSI impacts pregnancy outcomes and programs disease risk trajectories in offspring across the life course.

Laser therapy for twin-twin transfusion syndrome in a dizygotic monochorionic twin pregnancy: A case report.

OBJECTIVE: A monochorionic dizygotic (MCDZ) twin is rare, especially when complicated with twin-twin transfusion syndrome (TTTS) and treated by laser therapy. CASE REPORT: A pregnancy achieved from oocyte donation and intracytoplasmic sperm injection resulted in two embryos transferred. A monochorionic diamniotic twin pregnancy was diagnosed by an early ultrasound; however, at 16 weeks of gestation, instead of the same sex, the ultrasound suspected there was sex discrepancy between the twins. TTTS with severe polyhydramnios occurred at 22 weeks, leading to a laser therapy, which was followed with a smooth post-operation course. Then the Cesarean section was performed at the gestational age of 29 weeks due to severe preeclampsia, giving birth to two live newborns: one female and one male baby both without neurological sequelae at the time of discharge. Blood chromosomes obtained at delivery and 65 days after delivery all revealed an XX and XY chimera from both babies. CONCLUSION: Laser therapy is also effective in MCDZ twin complicated with TTTS. Determination of chorionicity in early pregnancy could timely prompt us to watch out for complications unique to monochorionic twin pregnancy.

Cytogenetic analysis of early pregnancy loss after assisted reproduction treatment using intracytoplasmic sperm injection.

OBJECTIVES: To evaluate the incidence of numerical chromosomal abnormalities in the patients with early pregnancy loss (EPL) following in vitro fertilization, and evaluate the role of different confounders of the risk of chromosomal abnormality-related pregnancy loss. MATERIAL AND METHODS: A retrospective chart review of all patients from our in vitro fertilization (IVF) center who conceived using assisted reproduction techniques between April 2017 and 2019, who experienced a subsequent early pregnancy loss, and whose abortus materials were successfully karyotyped were included. RESULTS: Of the 243 patients experienced an early loss, the overall rate of chromosomal abnormality was 46.75%. The overall rate of aneuploidy in our patient group was 88.8% (64/72), whereas 6.94% (5/72) of the abnormal karyotypes were polyploid. The most common type of trisomy was Trisomy 16 (20.0%; 11/55) followed by Trisomy 15 (14.5%; 8/55). Univariate and multivariate analyses showed that maternal age (< 35 years) and the total number of retrieved oocytes per cycle (≥ 5) were risk factors for a chromosomal abnormality (< 0.001; < 0.05, respectively). The adjusted OR of karyotypic abnormalities was 0.45 for the antagonist cycle type (p < 0.05), and 0.58 for frozen embryo transfer (p < 0.05). CONCLUSIONS: Karyotypic abnormality is one of the main reasons for pregnancy loss following an IVF procedure. Although the pregnancy rates increased as a result of novel technologies, the ratio of EPL is still high. The implementation of preimplantation genetic screening techniques might lower the incidence of EPL due to chromosomal abnormalities, thus decreasing the burden on the physicians and the patients.

Thin endometrium is associated with the risk of hypertensive disorders of pregnancy in fresh IVF/ICSI embryo transfer cycles: a retrospective cohort study of 9,266 singleton births.

BACKGROUND: Thin endometrial thickness (EMT) has been suggested to be associated with reduced incidence of pregnancy rate after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment, but the effect of thin endometrium on obstetric outcome is less investigated. This study aims to determine whether EMT affects the incidence of obstetric complications in fresh IVF/ICSI-embryo transfer (ET) cycles. METHODS: We conducted a retrospective cohort study collecting a total of 9266 women who had singleton livebirths after fresh IVF/ICSI-ET treatment cycles at the Center for Reproductive Medicine Affiliated to Shandong University between January 2014 and December 2018. The women were divided into three groups according to the EMT: 544 women with an EMT ≤8 mm, 6234 with an EMT > 8-12 mm, and 2488 with an EMT > 12 mm. The primary outcomes were the incidence of obstetric complications including hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), placental abruption, placenta previa, postpartum hemorrhage (PPH) and cesarean section. Multivariable logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for associations between the EMT measured on the day of human chorionic gonadotropin (HCG) trigger and the risk of the outcomes of interest. RESULTS: The HDP incidence rate of pregnant women was highest in EMT ≤ 8 mm group and significantly higher than those in EMT from > 8-12 mm and EMT > 12 mm group, respectively (6.8% versus 3.6 and 3.5%, respectively; P = 0.001). After adjustment for confounding variables by multivariate logistic regression analysis, a thin EMT was still statistically significant associated with an increased risk of HDP. Compared with women with an EMT > 8-12 mm, women with an EMT ≤8 mm had an increased risk of HDP (aOR = 1.853, 95% CI 1.281-2.679, P = 0.001). CONCLUSION: A thin endometrium (≤8 mm) was found to be associated with an increased risk of HDP after adjustment for confounding variables, indicating that the thin endometrium itself is a risk factor for HDP. Obstetricians should remain aware of the possibility of HDP when women with a thin EMT achieve pregnancy through fresh IVF/ICSI-ET treatment cycles.

Noninvasive preimplantation genetic testing for aneuploidy exhibits high rates of deoxyribonucleic acid amplification failure and poor correlation with results obtained using trophectoderm biopsy.

OBJECTIVE: To validate a commercially available noninvasive preimplantation genetic testing for aneuploidy (niPGT-A) assay by investigating the following: prevalence of deoxyribonucleic acid (DNA) amplification failure with niPGT-A; factors affecting amplification failure with niPGT-A; and frequency of discordant results between niPGT-A and traditional preimplantation genetic testing for aneuploidy. DESIGN: Prospective cohort study SETTING: Academic-affiliated private practice PATIENT(S): One hundred sixty-six blastocysts and their surrounding culture media from couples undergoing in vitro fertilization between July 2019 and May 2020 were analyzed. INTERVENTION(S): Blastocyst-stage spent culture media samples underwent niPGT-A using a commercially available kit that used whole-genome amplification with a modified multiple annealing and looping-based amplification cycle protocol followed by next-generation sequencing. Preimplantation genetic testing for aneuploidy of trophectoderm (TE) biopsies was performed using targeted next-generation sequencing. MAIN OUTCOME MEASURE(S): The primary outcome was failure to achieve an interpretable result with niPGT-A. Factors affecting DNA amplification were also assessed. Discrepancies between niPGT-A and TE biopsy results were analyzed, and clinical outcomes were evaluated. RESULT(S): Deoxyribonucleic acid amplification failures with niPGT-A were observed in 37.3% (62/166) of the samples. With TE biopsy, no embryos exhibited DNA amplification failure. Embryos with a shorter duration of exposure to the culture media and no evidence of whole-chromosome aneuploidy on the TE biopsy displayed high rates of DNA amplification failure with niPGT-A. Of 104 embryos with both niPGT-A and TE biopsy results available, whole-chromosome discordance was noted in 42 cases (40.4%). Three embryos classified as aneuploid based on the niPGT-A result progressed to successful delivery. CONCLUSION(S): The rates of DNA amplification failure were high among the niPGT-A samples, virtually precluding the clinical applicability of niPGT-A in its current form.

Does the Time of Starting Progesterone Luteal Support Affect Embryo Transfer in Long Agonist Protocol Downregulated ICSI Cycles? A Randomized Controlled Trial.

The aim of this study was to compare the effects of starting progesterone (P4) luteal support (LS) on day of egg retrieval (ER) or day of embryo transfer (ET) on the ratio of difficult ET and cycle outcome. This was a RCT ( ClinicalTrials.gov Identifier: NCT03040830) carried out at Mansoura Integrated Fertility Center (MIFC), Mansoura, Egypt, from November 2015 to January 2017. A total of 171 eligible long agonist ICSI cases were randomly allocated on day of ER into group A (86) starting LS as daily IM 100 mg P4 on day of ER and group B (85) starting P4-LS on day of ET. Difficult ET was defined as blood on ET catheter and/or sounding or dilating the cervix. Primary outcome was the overall ratio of difficult ET and ratios on day 3 and 5 ET. Secondary outcome was the ongoing pregnancy rate (OPR) and implantation rate (IR). The results are presented as % for groups A and B respectively: overall difficult ET (44.1, 24.7) (p = 0.009); day 3 difficult ET (23.2, 24.4) (p = 0.45); day 5 difficult ET (62.7, 25.6) (p = 0.001); overall OPR (38.3, 44.7) (p = 0.43); day 3 ET OPR (41.8, 33.3) (p = 0.51); day 5 ET OPR (34.8, 57.5) (p = 0.048); overall IR (20.0, 22.5) (p = 0.62); day 3 ET IR (17.8, 13.4) (p = 0.44); day 5 ET IR (22, 34.1) (p = 0.09). In conclusion, starting P4 luteal support on egg retrieval day is associated with significantly higher ratio of difficult embryo transfer and lower ongoing pregnancy rate and tendency to lower IR in day 5 ET, so starting P4-LS on day of ET is recommended.

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.

The uterine immune profile: A method for individualizing the management of women who have failed to implant an embryo after IVF/ICSI.

A unique endometrial immune reaction should occur to promote the human embryo implantation. We postulated that an immune disequilibrium may impact the initial dialogue between the mother and her embryo. In 2012, we set a method of uterine immune profiling for patients with unexplained repeated implantation failures (RIF). The method documents the local Th-1/ Th-2 equilibrium and the recruitment and state of maturation/activation of uNK cells. In function of the disequilibrium observed, personalization of assisted reproductive treatments was suggested. As the concept of personalization in function of the uterine immune profile had never been proposed, a large cohort study and a controlled cohort study were first conducted in RIF patients. 80 % of the RIF patients showed a local disequilibrium if compared to fertile controls. The local disequilibrium was identified in 3 categories: over-immune activation in 45 %, low- local immune activation in 25 % and mixed profile in 10 %. Personalization of treatments in function of the immune profile allowed to restore a live birth rate by 40 % at the following embryo transfer. RIF patients with endometriosis show some particularities regarding their immune profiles. We also suggested that immunotherapy (corticoids, intralipids) may have targeted indications based on a better understanding of the immune type of disequilibrium documented. Personalization of treatments for RIF patients seems to be essential to promote the subsequent live birth rate. The endometrial immune profiling is an innovative method aiming to detect a local immune disequilibrium and, if present, to test preventively its correction under treatment.

The association between fertility treatments and the incidence of paediatric cancer: A systematic review and meta-analysis.

BACKGROUND: It is important to explore the association between different fertility treatments and the incidence of paediatric cancer, as this will provide crucial guidance for clinical decision-making. Previous studies have explored the relationship between fertility treatments and different types of cancer in offspring, but the results are controversial. METHOD: Two authors searched PubMed, Embase, Web of Science and Cochrane databases independently to acquire qualified studies. Then, the same authors extracted data from these studies and analysed these data using RevMan 5.3. MAIN RESULTS: Eleven case-control studies and 16 cohort studies were included in this review and meta-analysis. The relative risk of association between in vitro fertilisation (IVF) and paediatric cancer incidence was 1.01 (95% confidence interval [CI]: 0.80-1.28) in cohort studies and 1.09 (95% CI: 0.74-1.58) in case-control studies. The relative risk of association between intracytoplasmic sperm injection (ICSI) and paediatric cancer incidence was 0.97 (95% CI: 0.80-1.17) in cohort studies. The relative risk of association between fertility drugs and paediatric cancer incidence was 1.07 (95% CI: 0.68-1.69) in cohort studies and 1.12 (95% CI: 0.90-1.41) in case-control studies. The relative risk of association between frozen embryo transfer and paediatric cancer incidence was 1.37 (95% CI: 1.04-1.81) in natural pregnancy controls and 1.28 (95% CI: 0.96-1.69) in fresh embryo transfer controls. CONCLUSION: There is no evidence that IVF, ICSI and fertility drugs are associated with an increase in paediatric cancer incidence in offspring; however, frozen embryo transfer is associated with an increase in paediatric cancer incidence in the offspring, but this finding needs further research and attention.

Use of phospholipase C zeta analysis to identify candidates for artificial oocyte activation: a case series of clinical pregnancies and a proposed algorithm for patient management.

OBJECTIVE: To investigate the applicability of phospholipase C zeta (PLCζ) analysis in assisting the clinical decision-making process when considering artificial oocyte activation (AOA) for infertile males in assisted reproductive technology. DESIGN: Fifty-six males (43 infertile/13 fertile) were screened using our PLCζ assay. SETTING: Fertility unit/university laboratory. PATIENT(S): Infertile males with abnormal sperm morphology or total fertilization failure, low fertilization rate (<50%), or repeated fertilization failure in assisted reproductive technology. INTERVENTION(S): We analyzed PLCζ levels in sperm from fertile and infertile males. Eligible patients subsequently underwent intracytoplasmic sperm injection (ICSI)/artificial oocyte activation (AOA) with calcimycin (GM508). MAIN OUTCOME MEASURE(S): PLCζ localization and level and the proportion of sperm expressing PLCζ. Thresholds of PLCζ deficiency, fertilization rates, pregnancy rates, and live birth rates of AOA and non-AOA cycles. RESULT(S): Compared with 13 fertile controls, 34 of the 43 infertile males had significantly lower levels of PLCζ and/or a significantly lower proportion of sperm exhibiting PLCζ. Of these 34 patients, 15 showed a significant PLCζ reduction in both parameters, which we termed "PLCζ deficiency." Five PLCζ-deficient patients opted for AOA; all five achieved fertilization, and four achieved clinical pregnancies and live births. The fertilization rate improved significantly from 18.6% (ICSI) to 56.8% (ICSI/AOA). The clinical pregnancy rate and live birth rate with AOA were both 40% per initiated cycle. Youden index analysis revealed that the cutoffs below which infertile males were likely to benefit from AOA were 71% for the proportion of sperm expressing PLCζ and 15.57 arbitrary units for mean PLCζ level. CONCLUSION(S): PLCζ analysis is a useful diagnostic tool to determine patient eligibility for subsequent AOA treatment.