In Vitro Fertilization Group Research Articles

Behavioral, Social, and Emotional Development of Five-Year-Old Children Conceived by Assistive Reproductive Technologies (In-Vitro Fertilization)

Preschool children conceived through In-Vitro Fertilization (IVF) tend to demonstrate particular behavioral, social, and emotional patterns that correlate with their physical development. The authors used a number of techniques to assess the behavior and social and emotional development of five-year-old IVF children. Such questionnaires as Your Child’s Behavior and Child’s Relationship with Friends and Family cast light on the behavioral, social, and emotional status. To define the physical development, the authors used such questionnaires as Child Feeding Issues, Three-Month History of Infectious Diseases, History of Injuries and Accidents, and Chronic Disease History. The sample consisted of 81 IVF children and 153 naturally-conceived children (aged 5); it included subgroups of children with perinatal developmental risks. Most parents of the IVF children reported neither behavioral nor social issues. However, the IVF children demonstrated more severe emotional issues. The IVF children with perinatal developmental risks had more pronounced emotional and anxiety issues, which was not typical of naturally-conceived children with perinatal risks. Both groups included children with difficulties in social and emotional development. The study revealed four significant factors that defined the difficulties of the socio-emotional development in the IVF children: behavioral disorders, aggression, social issues, and emotional issues. The significant correlations of behavioral, social, and emotional development in the IVF group indicated some specificity against the control. The correlating indicators of mental and physical development proved that physical development might affect behavioral, social, and emotional development in IVF children.

Endocrine Characteristics and Obstetric Outcomes of PCOS Patients with Successful IVF and Non-IVF Pregnancies.

Background/Objective: Infertility affects an estimated 40-50% of women with polycystic ovary syndrome (PCOS), the leading cause of anovulatory infertility, but only a small proportion of the patients require in vitro fertilization (IVF) therapy. Both PCOS and IVF are associated with an increased risk of obstetric complications. To compare preconception endocrine profiles and symptoms, as well as obstetric outcomes of PCOS patients who achieved successful pregnancies with and without IVF treatment. Methods: A single-center retrospective cohort study was conducted. Data spanning from 2012 to 2019 were compiled from patients with PCOS who visited the Gynecologic Endocrinology Unit and the Infertility Unit at the Department of Obstetrics and Gynecology, University of Debrecen. Patients diagnosed with PCOS who had had at least one successful delivery beyond the 23rd gestational week at the department were eligible for inclusion in the study. Results: Fifteen percent of the 206 pregnancies leading to successful deliveries of 232 newborns in our cohort conceived with IVF. A one year increase in the maternal age increased the odds of being in the IVF group by 22% (OR: 1.222, 95% confidence interval, CI: 1.11-1.35, p < 0.001). Baseline DHEAS and androstenedione levels were significantly lower in the IVF group as compared to the non-IVF group: 1 μmol/L increase in the DHEAS level decreased the odds of being in the IVF group by 18% (OR: 0.82, 95% CI: 0.66-1.01, p = 0.06), and 1 μg/L increase in the serum androstenedione concentration decreased the same odds by 42% (OR: 0.58, 95% CI: 0.33-1.02, p = 0.056). DHEAS levels <6.5 μmol/L had an OR 3.86 (95% CI 1.10-13.50, p = 0.04) and LH/FSH ratio <1.3 had an OR 3.58 (95% CI 1.18-10.81, p = 0.03) for being in the IVF group. The birth weight (3069 ± 683 g vs. 3362 ± 638 g, p = 0.02) and the gestational age (37.23 ± 2.55 vs. 38.54 ± 2.28 weeks, p = 0.004) were significantly lower in the IVF group, but in the singleton subgroups, no significant differences could be found. Birth weight percentiles showed no significant difference in either subgroup. In the IVF group, both preterm delivery (29% vs. 8.3%, OR 4.53, 95% CI 1.75-11.70, p = 0.002; singleton subgroup: 17.4% vs. 6.3%, OR 3.12, 95% CI 0.89-10.92, p = 0.07) and cesarean section (71% vs. 43.2%, OR 3.22, 95% CI 1.40-7.40, p = 0.006; singleton subgroup: 65.2% vs. 42.4%, OR 2.55, 95% CI 1.02-6.35, p = 0.04) were more frequent than in the non-IVF group. Gestational diabetes and preeclampsia were not significantly different in the IVF and non-IVF groups. Conclusions: In PCOS patients with successful pregnancies, those who conceive with IVF seem to be different in their baseline hormone levels and symptoms from the non-IVF group. Adverse obstetric outcomes are more common in the IVF group, and some of these differences persist when adjusting for singleton pregnancies and maternal age, too.

Single-cell RNA-sequencing analysis of the effects of frozen-thawed embryo transfer on the transcriptome of trophoblasts

Objectives: Frozen-thawed embryo transfer (FET) is widely used in in vitro fertilization (IVF) clinics but is associated with an increased risk of several pregnancy complications, including large-for-gestational age and placenta-related diseases. However, the effects of FET on placentation remain unclear. Therefore, we used single-cell RNA-sequencing (scRNA-seq) technology to investigate the impact of FET on placental gene expression in different subtypes of trophoblasts. Methods: A mouse model of IVF and FET was constructed to collect placenta tissues. scRNA-seq was performed on placentas from two dams undergoing IVF-embryo transfer and two dams undergoing IVF-FET. Differentially expressed gene (DEG) analyses were performed in different subtypes of trophoblasts. Identified DEGs were PCR validated. Results: The fetal weights and placental efficiency were higher in the FET group than those on the IVF group at E18.5, with no significant difference in placental weights. Subsequently, 55,406 placental cells were captured and annotated. Upregulated DEGs in the FET group in syncytiotrophoblasts (SynTs) and sinusoidal trophoblast giant cells (S-TGCs) within the placental labyrinth were enriched in pathways related to vascular development and oxidative stress, respectively. The expression of the imprinted gene Igf2 in SynTs, S-TGCs, and spongiotrophoblasts was significantly increased. In the junctional zone, FET upregulated the expression of prolactin genes such as Prl3b1 in glycogen trophoblasts (GlyTs) while the downregulated expression of GlyT genes following FET was associated with mesenchyme development. Conclusion: This study first identifies DEGs and enriched pathways in different subtypes of trophoblasts following FET. These genes and pathways may contribute to the increased placental efficiency and fetal weights. Future studies are required to confirm these results and further explore the key mechanisms in placental pathologies.

Comparative influence of inappropriate gestational weight gain on pregnancy outcomes in IVF-conceived and spontaneously conceived twin pregnancies.

To investigate the influence of inappropriate gestational weight gain (GWG) on pregnancy outcomes in twin pregnant women with invitro fertilization (IVF) treatment. This retrospective cohort study included 2992 twin pregnant women and categorized the participants as follows: (i) they were classified into spontaneous conception (SC) or IVF groups based on whether they received IVF treatment, and (ii) they were categorized into inadequate, optimal, or excessive GWG groups according to the International Organization for Migration Twin Pregnancy Guidelines. Initially, the study investigated the separate effects of IVF treatment and different levels of GWG on the outcomes of twin pregnancies. Subsequently, after adjusting for confounding factors, multifactorial logistic regression analysis was performed to further investigate the impact of IVF treatment and high GWG on twin pregnancy outcomes. Based on this, the analysis was stratified by whether IVF was used to explore the effects of different GWG levels on each subgroup (those who underwent IVF and those who conceived spontaneously). Finally, potential multiplicative interactions between IVF and different GWG categories were examined to identify their combined effect on pregnancy outcomes. The results showed that women with twin gestations conceived via IVF exhibited significantly higher maternal age, pre-pregnancy body mass index, and a greater incidence of GWG beyond recommended guidelines compared to the SC group. Furthermore, both IVF treatment and inappropriate GWG increased the risk of adverse pregnancy outcomes, respectively. Following adjustments for confounding variables through multifactorial logistic regression, it was demonstrated that both IVF treatment and high GWG significantly elevated the risk of adverse outcomes in twin pregnancies, such as admission to the neonatal intensive care unit. It is noteworthy that inappropriate GWG, combined with IVF treatment, will stepwise increase the incidence of intrahepatic cholestasis of pregnancy, respiratory failure, respiratory distress, pre-eclampsia, maternal intensive care unit admission, and postpartum hemorrhage risk. However, these outcomes were less affected by inappropriate GWG in the SC group. Lastly, this study did not unveil a significant interaction between the IVF procedure and disparate levels of GWG in relation to the adverse outcomes. A high incidence of inappropriate GWG in twin pregnancies with IVF treatment and inappropriate GWG conferred more adverse twin pregnancy outcomes in the IVF group relative to the SC group. This study indicates that proper management of GWG may be a breakthrough in reducing adverse outcomes in twin pregnancies associated with IVF. Therefore, implementing proactive interventions such as supervised exercise programs, prescribed physical or dietary plans, enhanced weight management, or personalized counseling, holds promise for lowering the risks associated with inappropriate GWG in twin pregnancies resulting from IVF.

Perinatal Outcomes of Singleton, Twin and Triplet Gestations after Oocyte Donation: A Retrospective, Population-Based Cohort Analysis.

Although high live birth rates are associated with oocyte donation (OD), these pregnancies are associated with increased obstetric and perinatal risks. This study evaluated maternal and neonatal risks after OD compared to in vitro fertilization (IVF) with autologous oocytes, and to spontaneous pregnancies (SPs), among singletons, twins and triplets. A retrospective, large, population-based cohort study was conducted based on electronic data from Maccabi Healthcare Services. A total of 469,134 pregnancies were grouped according to the mode of conception. The main outcome measures were preterm birth (PTB), small for gestational age (SGA) and pregnancy-induced hypertension (PIH). The data were analyzed separately for singletons, twins and triplets. The mean maternal age was older in the OD group compared with the IVF and SP groups (singletons: 39.7 ± 4.1 vs. 34.5 ± 4.8 and 31.7 ± 5.3 years; twins: 39 ± 4.6 vs. 32.6 ± 4.4 and 31.2 ± 5.1 years; and triplets: 35.6 ± 2.5 vs. 32 ± 3.9 and 29.7 ± 5 years). The mean gestational age was younger among the OD group compared to the SP group (singletons: 37.5 ± 3 vs. 39 ± 2 p = 0.001, and twins: 35 ± 3 vs. 36 ± 2.5 p = 0.001). Higher rates of PTB < 37, PTB < 34 and PTB < 28 weeks were found among OD singletons. Multivariable logistic regressions for PTB < 37 weeks and SGA in singletons demonstrated that OD and IVF are significant risk factors (OR = 4.1, 95%CI = 3.3-5.2; OR = 4.3, 95%CI = 4.1-4.6; OR = 1.9, 95%CI = 1.3-2.6; OR = 2.2, 95%CI = 2-2.4, respectively). Significantly higher rates of PIH were demonstrated among the OD vs. IVF and SP groups in singleton (4.3% vs. 1.7% and 0.7%) and in twin pregnancies (7.5% vs. 4.3% and 3.4%). OD pregnancies are at increased risk for PTB, SGA and PIH.

In Vitro Fertilization and Hearing Impairment in Twins.

This study investigates the potential correlation between in vitro fertilization (IVF) and hearing impairment in twins compared to naturally conceived twins. Analyzing data from 2416 twin infants born between 2019 and 2021. Analyze the pregnancy conditions and complications of mothers, the birth conditions of newborns, perinatal diseases, initial hearing screening results, and subsequent follow-up conditions. Our findings reveal that the incidence of hearing impairment in IVF-conceived twins is comparable to that in naturally conceived twins. Significant differences in low birth weight, preterm birth, respiratory distress syndrome, and hyperbilirubinemia were observed between infants who passed and referred the hearing screening (P ＜ 0.05). The IVF group exhibited a lower incidence of low birth weight (P < 0.05) and older maternal age (P < 0.05), while showing higher rates of placental abnormalities and placental abruption (P < 0.05). Notably, these distinctions did not translate into a significant impact on hearing impairment. Regardless of the method of conception, the following key factors contributing to hearing impairment in twins were identified: low birth weight, preterm birth, respiratory distress syndrome, and hyperbilirubinemia. IVF technology does not exert specific effects on hearing impairment in twins, with perinatal complications being the primary influencing factors.

P-776 School-age outcomes among IVF and ICSI -conceived children: a causal inference analysis using linked population-wide data

Abstract Study question What is the causal effect of method of oocyte insemination; standard in-vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI), on childhood development at school entry? Summary answer The developmental outcomes at school entry for children conceived by ICSI, without severe male factor infertility, are equivalent to those conceived via standard IVF. What is known already Over 12 million children have been conceived globally with the assistance of assisted reproductive technology (ART). Within ART, ICSI continues to increase as the most common mode of oocyte insemination, even when not clearly indicated (i.e. without male factor infertility). Large cohort studies have suggested that ART, and ICSI in particular, may be associated with an increase in congenital abnormalities, autism spectrum disorder, developmental delay and intellectual disability. However, the studies are heterogenous and the evidence conflicting. The association between the ICSI technique itself and long-term childhood development remains unclear. Study design, size, duration Causal inference methods were used to analyse observational data in a way that emulates a target randomised clinical trial. For example, patients where standard IVF was not an option, (e.g., due to severe male factor infertility), were excluded. The state-wide cohort included linked maternal and childhood administrative data from Victoria, Australia. To eliminate potential confounding associated with IVF, comparison was made with children conceived via standard IVF (rather than conception without assistance). Participants/materials, setting, methods The study included singleton infants conceived via ART and born between 2005-2013. The primary exposure was conception via ICSI, with those born following conventional IVF insemination as controls. The outcome examined was the Australian Early Development Census (AEDC), a broad assessment of development and well-being performed in Australian schools, every triennium, at school entry (age 4-6). We combined multiple imputation and inverse probability weighting with regression adjustment to estimate population average causal effects. Main results and the role of chance The final cohort included 4,035 IVF and ICSI conceived children across the two outcome cohorts. Linked records were available for 2,468 ICSI children and 1,567 IVF-conceived controls. Maternal characteristics between the two treatment cohorts were similar for age, parity, education, language background, and number of eggs collected during treatment cycle. The ICSI conceived children were generally from residential areas of lower socio-economic status and conception was more likely to involve donated gametes. The unadjusted rate of the primary outcome; AEDC-defined “developmental vulnerability”, was 10.83% among the IVF group and 10.14% among the ICSI group. Given the use of observational data, there were missing data and inherent differences in the covariate profile between exposure cohorts. Multiple imputation, bootstrapping and doubly robust inverse probability weighted regression adjustment modelling was utilised to allow a causal interpretation of results. There was no evidence of a causal effect of ICSI-conception on the risk of AEDC-defined developmental vulnerability at school entry compared with spontaneously conceived children; adjusted risk difference -0.8% (95% CI -2.7% to 1.1%) and adjusted risk ratio 0.92 (95% CI 0.76 to 1.12). The adjustment variable set was determined a priori via a modified Delphi procedure. Limitations, reasons for caution Children who did not attend school due to severe disability were excluded, leading to potential selection bias. Within our study cohort of 2,468 ICSI children, no increased risk of developmental vulnerability was identified. It is possible that unmeasured confounders could have led to bias in estimating the treatment effects. Wider implications of the findings This study, in contrast to previous evidence, suggests that empiric use of ICSI compared with conventional IVF insemination does not affect early childhood developmental outcomes. These findings provide important reassurance for current and prospective parents, and clinicians alike. Trial registration number not applicable

O-107 The contribution of women's modes of conception, self-mastery, perceived stress, and cognitive appraisal to personal growth in two phases during pregnancy

Abstract Study question How do women’s modes of conception, self-mastery, perceived stress, and cognitive appraisal contribute to personal growth during two phases of pregnancy? Summary answer Women who conceive through IVF experience the highest level of personal growth; Higher challenge appraisal is associated with higher personal growth in both study phases. What is known already Pregnancy can be experienced as a complex and stressful period, especially for women who conceive through fertility treatments. However, stress also constitutes an opportunity to experience personal growth, as shown by a few studies that examined women once during pregnancy. One study focused on cognitive appraisal and found that as women appraise their pregnancy as more challenging, they experience a higher level of growth during the third trimester of pregnancy. Additionally, scarce evidence indicates that personal growth increases from the third trimester to the postpartum period. Study design, size, duration The current study consists of three groups that differ in their modes of conception: spontaneous; first-line fertility treatments, such as intrauterine insemination (IUI); and in-vitro fertilization (IVF). A prospective design was employed in two phases during pregnancy: the first or second trimester (Phase 1; n = 400) and the third trimester (Phase 2; n = 268). Participants/materials, setting, methods Israeli pregnant women (age M = 32, SD = 4.5) were recruited by gynecologists and fertility specialists via several large women's health centers in Israel. Women completed five self-report questionnaires: Posttraumatic growth, self-mastery, perceived stress, cognitive appraisal, and questions relating to background and pregnancy-related details. Main results and the role of chance The findings indicate that women who conceived spontaneously have a higher sense of self-mastery than women who conceived through IVF. Whereas no differences were found between the study groups in perceived stress, the IVF group experienced higher personal growth than the spontaneous group during early pregnancy, but not during advanced pregnancy. The hierarchical regressions conducted to examine the contribution of the study variables to personal growth revealed that they accounted for 30.6% of its variance in the early phase of pregnancy and 23.6% in the advanced phase. In the early phase, lower self-mastery, a lower appraisal of the pregnancy as a threat, and a higher appraisal of the pregnancy as a challenge were associated with higher personal growth. In the advanced phase of pregnancy, only being first-time expecting mothers and higher challenge appraisal predicted personal growth. Finally, personal growth was greater in advanced pregnancy than in the earlier stage. Limitations, reasons for caution The findings rely on self-report measures, which may be biased. Also, the study was conducted in Israel, in which women who want to have children are eligible to receive fertility treatments sponsored by the health insurance fund up to the age of 44, thus should be considered in this context. Wider implications of the findings Women may experience positive implications following challenging conceiving circumstances. This can be translated to interventions aimed at strengthening women's internal resources and positive perceptions, as well as to raising awareness among professionals in fertility units that, alongside difficulties entailed in the process, it can also constitute an opportunity for growth. Trial registration number not applicable

Clinical significance for assessing adaptive hemostasis changes during multiple pregnancy after in vitro fertilization

Aim: to assess adaptive hemostasis changes in multiple dichorionic pregnancy after in vitro fertilization (IVF). Materials and Methods. A prospective observational randomized controlled trial was conducted by examining 58 and 46 pregnant women with multiple dichorionic diamniotic twins resulting from applying assisted reproductive technologies (ART) and spontaneous delivery (comparison group), respectively. Hemostasis parameters were studied as follows: activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen, antithrombin, protein C, protein S, functions of protein С (РrоС Global test), D-dimer, platelet aggregation with adenosine-5-diphosphate (ADP), ristocetin, and collagen. Results. A high coagulation potential was revealed, more prominent after using ART (p &lt; 0.05). Fibrinogen level gradually increased while gestation age increased, whereas APTT, PT and TT level decreased. In the group with natural conception, fibrinogen increased by 22 % in the second trimester, reaching 4.5 g/L (95 % CI = 4,2–4,8) and by 6 % in the third trimester, reaching 4.8 g/L (95 % CI = 4,3–5,4), whereas in the IVF group – by 26 %, reaching 5.3 g/L (95 % CI = 4,7–5,6) and by 21 %, reaching (6.5 g/L; 95 % CI = 5,2–6,8) in relevant trimester of pregnancy, respectively. Antithrombin level was lower in IVF patients – 76.8 % (95 % CI = 72.6 – 81.0) in the second trimester, reaching 70.6 % (95 % CI = 64.8–76.4) in the third trimester (p &lt; 0.001). Protein C level did not differ significantly between groups and was low within the reference range. The aggregatogram demonstrated a high platelet hemostatic potential in IVF patients (p &lt; 0.05) as early as in the first trimester: ADP-induced aggregation – 68.3 % (95 % CI = 62.9–73.7), ristocetin-induced aggregation – 53.1 % (95 % = CI 48.7–58.5), collagen-induced aggregation – 58.4 % (95 % CI = 52.1–64.7). In the third trimester, both platelet aggregation and functional activity (ADP-induced aggregation – 64.5 % [95 % CI = 59.3–69.7], ristocetin-induced aggregation – 68.4 % [95 % CI = 63.2–73.6], collagen-induced aggregation – 50.7 % [95 % CI = 44.3–57.1]; p &lt; 0.05) and D-dimer level persistently increased, also more prominently in the IVF group (1.60 ± 0.46 ng/ml; p &lt; 0.05). Conclusion. Gestational adaptation in induced multiple pregnancies is at high risk of breach in compensatory mechanisms and requires monitoring for timely detection of decompensation signs and their correction to prolong pregnancy till optimal delivery time frame.

Intracytoplasmic Sperm Injection Versus In vitro Fertilization in Infertile Women with Thyroid Autoimmunity.

Background: It has been reported that intracytoplasmic sperm injection (ICSI) may be the preferred fertilization method for women with thyroid autoimmunity (TAI) seeking assisted reproduction. We compared the reproductive outcomes of women with TAI who were treated with ICSI compared with in vitro fertilization (IVF). Methods: In this retrospective cohort study, we included women with infertility who were referred to the Reproductive Centre of Peking University Third Hospital for their first IVF/ICSI and embryo transfer (ET) treatment cycle from January 2019 to February 2021. In total, 2171 and 743 women with TAI underwent IVF and ICSI, respectively, while 8702 and 2668women without TAI underwent IVF and ICSI, respectively. We examined the cumulative live birth rate (primary outcome) from the initiated stimulative cycle as well as the secondary outcomes of fertilization rate, rates of clinical pregnancy, and live birth after the first ET cycle. We compared the reproductive outcomes of women treated with IVF and ICSI according to TAI status. Multivariable logistic regression analyses were performed to adjust for relevant confounders. Results: Women who underwent ICSI had significantly higher fertilization rates than those who underwent IVF (median [interquartile range]: 0.6 [0.5-0.8] in the TAI-positive and IVF group vs. 0.7 [0.5-0.8] in the TAI-positive and ICSI group vs. 0.6 [0.5-0.8] theTAI-negative and IVF group vs. 0.7 [0.5-0.8] in the TAI-negativeand ICSI group, p < 0.001). However, the rates of cumulative live births, clinical pregnancies, and live births were significantly lower among women with TAI who underwent ICSI than those who underwent IVF (cumulative live birth: 51.8% vs. 47%, adjusted odds ratio [aOR]: 0.80 [confidence interval, CI: 0.67-0.97]; clinical pregnancy: 43.0% vs. 38.8%, aOR: 0.81 [CI: 0.67-0.97]; live birth: 36.2% vs. 32.4%, aOR: 0.81 [CI: 0.66-0.98]). Conclusion: We observed that the use of ICSI in women with TAI was not associated with better assisted reproductive outcomes compared with IVF. Further prospective clinical trials are needed to confirm our findings.

Potential risk of gestational diabetes mellitus in females undergoing in vitro fertilization: a pilot study

BackgroundMost of the cases of hyperglycemia during pregnancy are attributed to gestational diabetes mellitus (GDM) (75–90%). Women diagnosed with GDM are at an increased risk for complications during pregnancy and delivery. This observational prospective study aimed to investigate the potential risk of GDM among Egyptian females following in vitro fertilization (IVF) pregnancies compared to spontaneous pregnancies (SC).MethodsThis prospective cohort study included normoglycemic females without any history of dysglycemia before this conception. Subjects were divided according to the type of conception into two age and BMI-matched groups: (IVF group): 55 pregnant females conceived by IVF, and (SC group) spontaneous pregnancy: 55 pregnant females conceived spontaneously. A one-step oral glucose tolerance test (OGTT) was performed at gestational weeks 20 and 28 for all study subjects.ResultsThe incidence of GDM was statistically significantly higher in the IVF group compared to the spontaneous pregnancy (SC) group (20 and 5.5%, respectively), p = 0.022 at week 28. On comparing the incidence of GDM on early screening at week 20 in both groups, the incidence of GDM in the IVF group was significantly higher (16.4%) compared to (3.6%) in the spontaneous pregnancy (SC) group, p = 0.026.ConclusionsIVF may have an increased potential risk for GDM. Moreover, the diagnosis of GDM may occur early (week 20), highlighting the need for precise and early screening for GDM in IVF pregnancies.

Obstetric and maternal outcomes of IVF and oocyte donation pregnancies among women ages 40–45—a large cohort study

PurposeTo analyze the perinatal and maternal outcomes of women ranging in age from 40 to 45 years who gave birth after in vitro fertilization or oocyte donation, compared to spontaneous conception.MethodsThis retrospective cohort study used electronic data from a national healthcare service from 2000 through 2019. Three groups were compared: spontaneous pregnancy (SC), in vitro fertilization (IVF) utilizing autologous oocytes, and pregnancies resulting from oocyte donation (OD). The primary study outcomes were preterm labor (PTL) before 37 weeks of gestation, and infants classified as small for gestational age (SGA).ResultsThe cohort included 26,379 SC, 2237 IVF pregnancies, and 300 OD pregnancies for women ages 40–45 years at delivery. Women with OD or IVF had a higher incidence of PTL < 37 weeks compared to women with SC (19.7% vs. 18% vs. 6.9%, p = 0.001), PTL < 34 (7% vs. 4.5% vs. 1.4%, p = 0.001), PTL < 32 (3.7 vs. 2.1 vs. 0.6, p = 0.001). A multivariable logistic regression for PTL < 37 weeks demonstrated that age (OR = 1.18) and hypertensive diseases (OR = 3.4) were statistically significant factors. The OD group had a lower rate of SGA compared to SC (1% vs. 4.3%, p = 0.001), while the IVF group had a higher rate of SGA compared to SC (9.1% vs. 4.3%, p = 0.001). Hypertensive diseases in pregnancy were significantly higher among the OD group and the IVF group compared to SP pregnancies (3.3% vs. 1%, p = 0.002; 2.3% vs. 1%, p = 0.001, respectively).ConclusionsWomen ages 40–45 undergoing IVF or OD have a greater risk of PTL, possibly due to higher rates of hypertensive disorders of pregnancy.

Intracytoplasmic sperm injection versus conventional in-vitro fertilisation for couples with infertility with non-severe male factor: a multicentre, open-label, randomised controlled trial

Introduced in 1992, intracytoplasmic sperm injection (ICSI) was initially indicated for severe male infertility; however, its use has since been expanded to non-severe male infertility. We aimed to compare the efficacy and safety of ICSI versus conventional in-vitro fertilisation (IVF) in couples with infertility with non-severe male factor. We conducted an investigator-initiated, multicentre, open-label, randomised controlled trial in ten reproductive medicine centres across China. Couples with infertility with non-severe male factor without a history of poor fertilisation were randomly assigned (1:1) to undergo either ICSI or conventional IVF. The primary outcome was live birth after first embryo transfer. We performed the primary analysis in the intention-to-treat population using log-binomial regression models for categorical outcomes or linear regression models for continuous outcomes, adjusting for centre. This trial is registered with Clinicaltrials.gov, NCT03298633, and is completed. Between April 4, 2018, and Nov 15, 2021, 3879 couples were screened, of whom 2387 (61·5%) couples were randomly assigned (1184 [49·6%] to the ICSI group and 1203 [50·4%] to the conventional IVF group). After excluding couples who were ineligible, randomised twice, or withdrew consent, 1154 (97·5%) in the ICSI group and 1175 (97·7%) in the conventional IVF group were included in the primary analysis. Live birth after first embryo transfer occurred in 390 (33·8%) couples in the ICSI group and in 430 (36·6%) couples in the conventional IVF group (adjusted risk ratio [RR] 0·92 [95% CI 0·83-1·03]; p=0·16). Two (0·2%) neonatal deaths were reported in the ICSI group and one (0·1%) in the conventional IVF group. In couples with infertility with non-severe male factor, ICSI did not improve live birth rate compared with conventional IVF. Given that ICSI is an invasive procedure associated with additional costs and potential increased risks to offspring health, routine use is not recommended in this population. National Natural Science Foundation of China, National Key Research and Development Program, Beijing Municipal Science & Technology Commission, and Peking University Third Hospital.

Fertilization, pregnancy, and neonatal outcomes after IVF, rescue ICSI, and ICSI in unexplained infertility: A retrospective study

AbstractConventional intracytoplasmic sperm injection (ICSI) is not recommended for nonmale infertile patients to avoid fertilization failure (FF) in view of controversies regarding safety issues. Among the strategies that may help to promote the use of in vitro fertilization (IVF) for women with a high risk of FF, rescue ICSI (R‐ICSI) has attracted attention. This study aimed to evaluate the efficacy of short‐term insemination combined with early R‐ICSI in the treatment of unexplained infertility. A total of 952 controlled ovarian stimulation (COS) cycles for unexplained infertility were divided into short‐term IVF (short‐term insemination without R‐ICSI, n = 500), R‐ICSI (short‐term insemination with R‐ICSI, n = 141), and ICSI (conventional ICSI, n = 311) groups. Patients underwent consecutive transfer cycles until live birth, or until all embryos from the first COS cycle were used. Laboratory data and clinical outcomes from short‐term IVF, R‐ICSI, and ICSI groups were compared. Short‐term IVF and ICSI groups were superior to R‐ICSI group in polyspermy rate, available embryo rate, and top‐quality embryos rate. Short‐term IVF, R‐ICSI, and ICSI groups underwent 705 (500 fresh and 205 frozen‐thawed cycles), 190 (141 fresh and 49 frozen‐thawed cycles), and 445 (311 fresh and 134 frozen‐thawed cycles) transfer cycles, resulting in 294, 76, and 190 live birth cycles, respectively. Comparison of pregnancy outcomes among these three groups demonstrated similar clinical pregnancy rates and live birth rates in fresh and frozen‐thawed embryo transfer cycles. There was no significant difference in the cumulative live birth rate among these three groups. R‐ICSI group showed similar neonatal outcomes compared with short‐term IVF and ICSI groups, including the rates of low birth weight, fetal macrosomia, small for gestational age and large for gestational age. Short‐term insemination combined with early R‐ICSI achieved satisfactory pregnancy and neonatal outcomes, albeit with a high polyspermy rate, which was an effective alternative to avoid excessive use of ICSI in unexplained infertility.

Serum erythropoietin level is increased during stimulation for IVF but not in OHSS

BackgroundErythropoietin (Epo) is a potent vascular growth factor that induces angiogenesis and antiapoptotic signalling. We investigated whether the development of numerous follicles and corpora lutea during in vitro fertilization (IVF) cycle affects circulating Epo levels and further, if Epo could be used as a novel marker for ovarian hyperstimulation syndrome (OHSS).Methods24 women were included in the uncomplicated IVF group and 35 women in the OHSS group. Repeated blood samples from both groups were analysed for Epo, progesterone, blood haemoglobin, and creatinine. Follicular fluid from the IVF group was analysed for Epo and progesterone. Repeated measure analysis was performed for the variables and circulating Epo levels were compared between the IVF group and early OHSS. Furthermore, related growth factors, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF-1) were analysed from subgroup of women to test for correlation with Epo.ResultsDuring IVF, circulating Epo increased from natural mid-luteal phase to stimulated mid-luteal phase (median 9.5; 95% CI 7.2–13.4 IU/L and 12.5; 10.3–13.4 IU/L; p = 0.003). In cycles resulting in pregnancy, Epo level decreased 14 days after oocyte pick-up (OPU) and remained low thereafter. In cycles not resulting in pregnancy, Epo level increased again 35 days after OPU. Follicle fluid Epo concentration was 1.5 times higher than the serum concentration (median 15.4; 95% CI 10.4–19.2 IU/L vs. 10.2; 8.8–12.7; p = 0.006). There was no difference in circulating Epo concentration between early OHSS and uncomplicated IVF. Circulating Epo did not correlate with VEGF or HIF-1.ConclusionsCirculating Epo levels fluctuate during IVF cycle. We hypothesise this may suggest Epo’s involvement in ovarian physiology and angiogenesis. However, Epo was not a clinical marker for OHSS.

Maternal and neonatal outcomes of intrahepatic cholestasis of pregnancy after in vitro fertilization

BackgroundIntrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease of pregnancy. Little is known about how it specifically affects pregnancies resulting from in vitro fertilization (IVF). Our aim is to evaluate the impact of IVF on the perinatal outcomes of ICP.MethodsA retrospective study of 242 patients with intrahepatic cholestasis of pregnancy, comprising 36 conceived through IVF and 206 spontaneous conceptions (SC), enrolled between 2019 and 2021 was carried out. Data were analyzed from the medical archives of the Huazhong University of Science and Technology, Tongji Hospital.ResultsNumerical values of transaminases (ALT, alanine aminotransferase; AST, aspartate aminotransferase) and serum total bile acid (TBA) are significantly lower in the IVF group than that in the spontaneous conceived group (p < 0.05). The incidence of gestational diabetes mellitus (GDM) was higher in the IVF group than in SC group (30.6% vs. 16%, p = 0.037). The cesarean section (CS) rates are higher in the IVF group (97.2% vs. 85.4%, p = 0.023). On the other hand, the prevalence of premature rupture of membranes (PROM) was higher in the SC group (10.7%) while none was reported in the IVF-ICP group. Other maternal comorbidities and neonatal outcomes were similar between the two groups.ConclusionICP patients who underwent IVF are more likely to suffer from GDM. Therefore, monitoring and management of blood glucose should be strengthened during pregnancy. Fortunately, IVF does not seem to worsen the progression or outlook of ICP, so sticking to standard management practices is recommended.

Sperm DNA fragmentation index affect pregnancy outcomes and offspring safety in assisted reproductive technology

The role of sperm DNA fragmentation index (DFI) in investigating fertility, embryonic development, and pregnancy is of academic interest. However, there is ongoing controversy regarding the impact of DFI on pregnancy outcomes and the safety of offspring in the context of Assisted Reproductive Technology (ART). In this study, we conducted an analysis of clinical data obtained from 6330 patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) at the reproductive medical center of The First People's Hospital of Shangqiu and The Affiliated Hospital of Zhengzhou University. The patients was stratified into two distinct groups: IVF group and ICSI group, Within each group, patients were further classified into three subgroups. IVF: group A (< 15%) included 3123 patients, group B (15–30%) included 561 patients, and group C (≥ 30%) included 46 patients. ICSI: group A (< 15%) included 1967 patients, group B (15–30%) included 462 patients, and group C (≥ 30%) included 171 patients. Data were collected and subjected to statistical analysis. There were no significant differences in the basic characteristics among the three groups, and the sperm DFI did not significantly affect the fertilization rates, pregnancy rates, stillbirth rates and the number of birth defects. However, the incidences of miscarriage rates in IVF/ICSI groups with DFI > 30% and DFI 15–30% were significantly higher than those in IVF/ICSI groups with DFI < 15%, and the miscarriage rates in ICSI group with DFI > 30% were significantly higher than DFI 15–30% group, the smooth fitting curve shows that there is a positive correlation between miscarriage rates and sperm DFI (OR 1.095; 95% CI 1.068–1.123; P < 0.001). The birth weight of infants in the IVF/ICSI groups with DFI > 30% and DFI 15–30% exhibited a statistically significant decrease compared to those in the IVF/ICSI groups with DFI < 15%. Furthermore, the birth weight of infants in the ICSI group with DFI > 30% was lower than that of the DFI 15–30% group. The smooth fitting curve analysis demonstrates a negative association between birth weight and sperm DFI (OR 0.913; 95% CI 0.890–0.937; P < 0.001). Sperm DFI has an impact on both miscarriage rates and birth weight in assisted reproductive technology. The smooth fitting curve analysis reveals a positive correlation between miscarriage rates and DFI, while a negative correlation is observed between birth weight and DFI.

Increased Y Chromosome Microdeletions in Cord Blood of Male Newborns From Assisted Reproductive Technology Compared to Natural Conception

ObjectivesTo investigate the incidence of Y chromosome microdeletions in male newborns conceived by intracytoplasmic sperm injection (ICSI), in vitro fertilization (IVF), and natural conception (NC). MethodsA total of 186 male newborns were recruited, including 35 conceived by ICSI, 37 conceived by IVF, and 114 conceived naturally. DNA was extracted from umbilical cord blood after birth. The Yq genetic status of the newborns was determined according to 18 Y-specific sequence tagging sites (STS) markers covering 3 azoospermia factor (AZF) sub-regions and internal control sequences. ResultsPartial AZF microdeletions were identified in 8 of 35 (22.9%) ICSI newborns, 4 of 37 (10.8%) IVF newborns, and 1 of 114 (0.9%) NC newborns. There was a statistically significant difference in the proportion of newborns with partial Y chromosome microdeletions between the ICSI, IVF, and NC groups. When analyzed individually, only the SY114 and SY152 STS markers showed a statistically significant difference in incidence between the 3 cohorts. ConclusionsOur study indicates that the population of male children conceived through assisted reproductive technologies (ART), particularly ICSI, is at an increased risk of genetic defect in the form of partial Y chromosome microdeletions. The growing population of ART-conceived children emphasizes the importance of studying the genetic repercussions of these procedures regarding the future fertility of males conceived in vitro.

Oocyte activation with phospholipase Cζ mRNA induces repetitive intracellular Ca2+ rises and improves the quality of pig embryos after intracytoplasmic sperm injection.

For the intracytoplasmic sperm injection (ICSI) procedure in pigs, an electrical pulse (EP) has been used as an effective method for oocyte stimulation, but unlike sperm, EP is unable to induce Ca2+ oscillations. In this study, we investigated the effects of generating artificial Ca2+ oscillations with phospholipase Cζ (PLCζ) mRNA, a candidate sperm factor, on fertilization, embryonic development, and gene expression after ICSI. Firstly, the concentration of PLCζ mRNA of a fixed volume (1.0 pl) that would induce a pattern of Ca2+ rise similar to that of in vitro fertilized (IVF) sperm was examined and determined to be 300 ng/μl. Secondly, the effects of oocyte stimulation methods on fertilization and embryonic development were investigated. ICSI-oocytes were activated by EP (EP group) or by PLCζ mRNA (PLCζ group). Furthermore, IVF-oocytes (IVF group) and ICSI-oocytes with and without an injection of buffer (buffer and untreated groups, respectively) were used as controls. It was found that the rates of normal fertilization in the PLCζ and EP groups were significantly higher than those in the buffer and untreated groups. The blastocyst formation rates did not differ among the groups. The embryo quality in the EP group was inferior to those in the PLCζ and IVF groups. Additionally, the expression level of a proapoptosis-related gene (Caspase-3) in the EP group was significantly higher than those in the PLCζ and IVF groups. Our data suggest that oocyte activation by PLCζ mRNA has the effect of improving embryo quality.

Efficacy of electro-acupuncture on pregnancy outcomes for women undergoing in vitro fertilization: study protocol for a pilot randomized controlled trial.

In vitro fertilization (IVF) is a technology that assists couples experiencing infertility to conceive children. However, unsuccessful attempts can lead to significant physical and financial strain. Some individuals opt for electro-acupuncture (EA) during IVF, even though there is limited evidence regarding the efficacy of this practice. Thus, this pilot study aims to explore the effectiveness and safety of EA during IVF on pregnancy outcomes. This clinical trial is a parallel, randomized, sham-controlled study. It aims to include a total of 118 infertile women who intend to undergo IVF. The participants will be randomly divided into three groups in a 1:1:1 ratio: the EA + IVF group, the placebo electro-acupuncture (pEA) +IVF group, and the IVF control group. All of the patients will be required to use ovarian stimulation drugs, while those in the EA + IVF and pEA + IVF groups will receive acupuncture treatment at three sessions per week (every other day) until trigger day with a minimum five session. The primary outcome of this trial will focus on the clinical pregnancy rate (CPR). CPR is defined as the rate of achieving clinical pregnancy from the first fresh/frozen embryo transfer cycle with an ultrasound-confirmed gestational sac in the uterine cavity. The secondary outcomes will assess embryology data, biochemical pregnancy rate, early miscarriage rate, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Fertile Quality of Life (FertiQoL), patient retention rate, treatment adherence, and safety outcomes. Ethics approval was obtained from the Ethics Committee of Sichuan Jinxin Xi'nan Women and Children Hospital (number 2021-007). The results will be disseminated through peer-reviewed publications. The participants gave informed consent to participate in the study before taking part in it. https://www.chictr.org.cn, identifier ChiCTR2300074455.