Prevention of multiple pregnancies by restricting the number of transferred embryos: randomized control study

Introduction The high incidence of multiple pregnancies is a major concern in the treatment of infertility by in vitro fertilization (IVF). Risks and costs are associated with multiple pregnancies and it is important to find a way to decrease multiple pregnancies. The standard protocol for IVF includes the transfer of two or three embryos.Methods In this study, we compared the rate of single and multiple pregnancies between patients who received two and three embryos. One hundred and sixty-nine patients were randomly divided into two groups, with 106 cycles of IVF each. Group 1 received two embryos, and group 2 three.Results Group 1 had total 40 (37.8%) pregnancies, while group 2 had 29 (27.4%). The number of ongoing pregnancies was 33 (31.1%) in group 1 and 26 (24.5%) in group 2. The number of baby-take-home was 32 (30.1%) in group 1 and 26 (24.5%) in group 2. These results show that there was no significant difference between the two groups in both the total and ongoing pregnancies. On the other hand, the number of twin pregnancies was 6 (15.0%) in group 1 and 12 (41.4%) in group 2, showing a significant difference. Group 1 had no triplet pregnancies, while Group 2 had two.Conclusion We conclude that the transfer of two embryos reduces the incidence of multiple pregnancies while maintaining an acceptable rate of pregnancy in IVF.     

Recent cadmium exposure among male partners may affect oocyte fertilization during in vitro fertilization (IVF)

Purpose  

We recently reported evidence suggesting associations between urine cadmium concentrations, reflecting long-term exposure, measured in 25 female patients (relative risk = 1.41, P = 0.412) and 15 of their male partners (relative risk = 0.19, P = 0.097) and oocyte fertilization in vitro. Blood cadmium concentrations reflect more recent exposure.     

Perceptions among infertile couples of lifestyle behaviors and in vitro fertilization (IVF) success

Purpose

To assess how patients perceive various lifestyle behaviors impact IVF success.

Methods

Cross-sectional study of heterosexual, English-speaking couples (n = 138) who completed web-based surveys during IVF treatment cycle. Perceived impact of lifestyle choices assessed by multivariable logistic regression and p-value tests for linear trend (P_t).

Result(s)

During the IVF cycle, most patients consider it helpful for women to exercise (76 %), avoid stress (87 %) and limit activity after embryo transfer (92 %). The majority of patients (62 %) consider rigorous exercise (4+ h/week) helpful and nearly one-third (32 %) perceive benefit to complete bed rest after transfer. Overall, couples with a sex-specific infertility diagnosis are more likely to consider partner’s lifestyle choices impactful: male-factor couples are more likely to consider it helpful for men to limit cellular phone use (OR:2.73,CI:1.06–7.04) and diminished ovarian reserve couples are more likely to consider it helpful for women to limit exposure to plastics (OR:2.38,CI:1.03–5.51). Patients at higher levels of education (P_t < 0.01) and income (P_t < 0.01) are less likely to consider lifestyle impactful.

Conclusion(s)

Patient perceptions of the impact of lifestyle factors on IVF success vary by sex, infertility diagnosis and socioeconomic factors. Despite counseling to the contrary, many patients perceive benefit to rigorous exercise during the IVF cycle and complete bedrest following transfer. Results provide insight into patient beliefs and highlight opportunities to improve patient education, alleviate patient anxieties and potentially improve IVF outcomes.     

Risk of spontaneous preterm birth in IVF-conceived twin pregnancies

Objective: To compare the mean transvaginal ultrasound (TVU) cervical length (CL) at midtrimester in screening for preterm birth in in vitro (IVF)-conceived twin pregnancies versus spontaneously-conceived twin pregnancies.

Methods: This was a retrospective cohort study. Potential study subjects were identified at the time of a routine second trimester fetal ultrasound exam at 18 0/7 to 23 6/7-week gestation. All women with twin diamniotic pregnancies screened with a single TVU CL for this trial were included. Mean TVU CLs were compared between IVF-conceived twin pregnancies and spontaneously-conceived twin pregnancies. The relationship of TVU CL with gestational age at delivery was assessed. Incidence of short TVU CL, defined as TVU CL ≤30?mm, was also calculated in the two groups. The primary outcome was the mean of TVU CL. Distribution of CL was determined and normality was examined in both groups

Results: A total of 668 women with diamniotic twin pregnancies who underwent TVU CL screening between 18 0/6 and 23 6/7 weeks were included. 158 (23.7%) were IVF-conceived pregnancies, and 510 (76.3%) were spontaneously-conceived pregnancies. No women received progesterone, pessary, or cerclage for preterm birth prevention during pregnancy. The mean TVU CL was significantly lower in the IVF-conceived group (32.2?±?10.5?mm) compared to the spontaneously-conceived group (34.1?±?9.1?mm) (mean difference (MD)???1.90?mm, 95%CI ?3.72 to ?0.08). The incidence of TVU CL ≤30?mm was 30.4% in the IVF-conceived group and 21.6% in the spontaneously-conceived group (adjusted odds ratio (aOR) 1.59, 95%CI 1.06–2.37). IVF-conceived twins had a significantly higher risk of spontaneous preterm birth <34 weeks (32.9 versus 21.2%; aOR 1.83, 95% confidence interval (CI) 1.23–2.71) and higher rate of delivery due to spontaneous onset of labor (64.5 versus 54.9%; aOR 1.50, 95%CI 1.03–2.17). For any given TVU CL measured between 18 0–7 and 23 6/7 weeks, gestational age at delivery for IVF-conceived twins was earlier by about 1 week on average compared with spontaneously-conceived twins.

Conclusions: The higher rate of spontaneous preterm birth in IVF-conceived twin pregnancies is predicted by lower midtrimester TVU CL, as well as by the lower gestational age at birth per any given CL in the IVF-conceived compared to the spontaneously-conceived twin pregnancies.     

Phospholipase C-zeta deficiency as a cause for repetitive oocyte fertilization failure during ovarian stimulation for in vitro fertilization with ICSI: a case report

Purpose

The purpose of this study is to describe impaired oocyte fertilization from phospholipase C-zeta (PLC-ζ) deficiency in normal-appearing sperm that was successfully treated using calcium (Ca²⁺) ionophore with intracytoplasmic sperm injection (ICSI) of oocytes matured in vitro.

Methods

An infertile couple undergoing in vitro fertilization (IVF) experienced failed oocyte fertilization following ICSI with normal-appearing sperm. A semen sample collected from the patient was used to assess the expression of sperm PLC- ζ protein by Western blot analysis and immunofluorescence and PLC-ζ bioactivity by an in vitro model of Ca²⁺ release. A second IVF cycle was performed using Ca²⁺ ionophore with ICSI to enhance Ca²⁺-induced oocyte activation of oocytes matured in vitro.

Results

Sperm PLC-ζ protein deficiency was demonstrated by Western blot analysis and immunofluorescence and confirmed by reduced PLC-ζ bioactivity using an in vitro model of Ca²⁺ release. Nevertheless, with this sperm and supplementation of Ca²⁺ ionophore following ICSI, fertilization of four of six oocytes matured in vitro was obtained. In addition, four embryos underwent cleavage and two of them reached the blastocyst stage. Transfer of these blastocysts into the uterus led to a single pregnancy and live birth.

Conclusions

Deficiency of PLC-ζ in normal-appearing human sperm is associated with impaired Ca²⁺-dependent oocyte activation during ICSI. Under this condition, use of Ca²⁺ ionophore following ICSI of oocytes matured in vitro improves embryo developmental competence, possibly through the activation of Ca²⁺-dependent mechanisms governing fertilization and preimplantation embryogenesis.     

Fetal and neonatal alloimmune thrombocytopenia in pregnancies involving in vitro fertilization: a report of four cases

OBJECTIVE: We report four cases of neonatal alloimmune thrombocytopenia (NATP) in pregnancies achieved with in vitro fertilization. STUDY DESIGN: Three cases used surrogate carriers, and the fourth a donor egg. Sera from gestational carriers were tested for platelet antibodies by flow cytometry and enzyme-linked immunosorbent assay. Platelet antigen genotyping of biologic mothers, fathers, and surrogates was performed by amplification of DNA by using polymerase chain reaction with sequence-specific primers. RESULTS: In all 4 cases, NATP resulted from an incompatibility between the fetus and gestational carrier for the platelet-specific alloantigen HPA-1a. Four infants were born severely thrombocytopenic (platelets <50,000/muL), 2 had antenatal intracranial hemorrhage, and 1 fetus expired in utero at 29 weeks. CONCLUSION: NATP can occur in the setting of assisted reproductive technology. Because of the great costs, both financial and emotional, associated with these pregnancies, we strongly recommend that all women be typed for HPA-1a before serving as a surrogate mother.     

Superovulation, in vitro fertilization (IVF) and in vitro development (IVD) protocols for inbred BALB/cJ mice in comparison with outbred NMRI mice

Purpose

To study assisted reproductive technology (ART) protocols including superovulation, in vitro fertilization (IVF) and in vitro development (IVD) for BALB/cJ mice in comparison with a common ART protocol for NMRI mice.

Methods

Adult NMRI and BALB/cJ mice were superovulated using a 48?h G-interval. In order to find a more suitable G-interval for the BALB/cJ strain, G-intervals including 44, 46 and 50?h were also examined. Superovulation rates were recorded in all groups. IVF rate of BALB/c oocytes in T6 and mHTF media were compared. IVD rates of BALB/cJ zygotes in mHTF, T6 and G1V₅/G2V₅ media were compared. In addition, IVF and IVD rates of BALB/cJ and NMRI oocytes were compared in T6 medium during IVF?CIVD procedures.

Results

In BALB/cJ mice the highest superovulation rates were observed with 44?C46?h G-intervals. However, with a 48?h G-interval, superovulation rates were significantly lower in BALB/cJ compared to NMRI mice (p?<?0.05). mHTF medium significantly increased in vitro fertilization of BALB/cJ oocytes compared to T6 medium (p?<?0.05). Fertilization rate of NMRI oocytes was significantly higher than BALB/cJ oocytes in T6 medium (p?<?0.05). The BALB/cJ embryo IVD was significantly higher in G1/G2 medium compared to mHTF and T6 media (p?<?0.01).

Conclusions

Superovulation with 48?h G-interval and using T6 during all in vitro procedures produces embryos more efficiently for NMRI mice than for BALB/cJ mice. For BALB/cJ mice, a protocol including superovulation with a 44?C46?h G-interval, using mHTF during IVF and G1V₅/G2V₅ medium during IVD, may improve in vitro embryo production.     

Triploidy after in vitro fertilization: Cytogenetic analysis of human zygotes and embryos

Tripronuclear zygotes obtained from a clinical IVF program were studied cytogenetically. Successful analysis was possible of 42 specimens at the zygote stage and 21 embryos after the first or second cleavage division. In the majority of zygotes (88%) the expected triploidy was confirmed, whereas only 14% of embryos had solely triploid cells. Therefore it is concluded that after tripolar cleavage division, many different types of mosaicism may originate from irregular chromosome distributions. Since the findings in individual blastomeres in embryos resulting from multipronuclear zygotes do not reflect the genetic content of the whole embryo, these embryos are less suitable in a model system for preimplantion diagnosis. The distribution of the sex chromosomal types (XXX, XXY, and XYY) confirmed theoretical expectations. Since in abortion material or in liveborn triploidy cases, the XYY karyotype is hardly ever observed, this indicates that most likely the 69,XYY karyotype has a very high embryonic mortality.     

不同精子来源及授精方式对剩余胚胎继续囊胚培养结局的影响

目的:探讨不同精子来源及不同授精方式对胚胎继续发育能力的影响。方法:分析499例患者499个取卵周期剩余胚胎继续培养形成囊胚的情况,按精子来源不同分为供精IVF(D-IVF)组和夫精IVF(H-IVF)组,按授精方式不同分为IVF组和ICSI组,ICSI组按精子来源分为新鲜精液组、附睾精子和睾丸精子组,比较不同精子来源及授精方式获得剩余胚胎的囊胚形成率、胚胎利用率和无囊胚移植率。结果:① D-IVF组和H-IVF组受精率、卵裂率、优质胚胎率、第3日和第5日胚胎种植率、临床妊娠率和流产率均无统计学差异(P0.05),组间剩余胚胎囊胚形成率、胚胎利用率和无囊胚移植率亦无统计学差异(P0.05);②ICSI组与IVF组比较,其受精率较高(P0.05),但优质胚胎率显著下降,有统计学差异(55.11%vs 61.30%,P0.05),组间第3日卵裂期胚胎和剩余胚胎囊胚种植率、临床妊娠率无统计学差异(P0.05),但ICSI组与IVF组比较,其剩余胚胎囊胚形成率、胚胎利用率稍低,无囊胚移植率较IVF组稍高,差异有统计学意义(56.13%vs 65.32%,48.18%vs 55.39%,21.68%vs 13.20%,P0.05)。③新鲜精液组的优质胚胎率、胚胎利用率显著低于附睾精子和睾丸精子组(P0.05),各组囊胚移植的种植率和临床妊娠率无统计学差异(P0.05)。结论:D-IVF可获得H-IVF相似的结局,其剩余胚胎都有较高的发育潜能,ICSI获得的剩余胚胎发育潜能低于IVF组。附睾精子和睾丸精子ICSI后获得的胚胎比新鲜精液精子ICSI后胚胎发育潜能高。针对不同的授精方式可能需要制定相应的剩余胚胎囊胚培养标准。     

Toward understanding women's decisions to continue or stop in vitro fertilization: The role of social,psychological, and background factors

Two hundred fifty-four infertile women, all of whom had at least one in vitro fertilization-embryo transfer (IVFET) cycle, completed a structured questionnaire in which they provided background information and rated their beliefs about the outcomes of continuing on an IVF-ET program. Women not intending to continue IVF had older husbands, a larger proportion was mothers, and more of them, had an IVF pregnancy. Those stopping and continuing, however, did not differ in their ages, the length of their infertility, or their number of IVF attempts. Women's intentions about IVF were best predicted by their attitudes toward another attempt and their perceptions of social pressures. While women intending to continue or discontinue IVF had similar beliefs about the value of motherhood, the satisfactions in having children, the importance of happy marriages, and the need to be well adjusted; discontinuers were less optimistic about another attempt making them mothers, making their marriages happier, or improving the quality of their lives. Both groups of women, however, judged another IV attempt as likely to involve some stress, disappointment, and financial strain. In terms of their perceptions of social pressures, discontinuers also believed that their husbands, family, friends, and doctors did not think that they should have another IVF attempt. Finally, infertile women's attitudes about having another attempt and their perceptions of social pressures to try again or to stop were better predictors of their decisions about IVF than the background characteristics and fertility histories of women and their husbands. At the same time, together these variables explained only half of the variance in women's IVF decisions, and many other factors need to be considered in future research.     

A formula for scoring human embryo growth rates in in vitro fertilization: Its value in predicting pregnancy and in comparison with visual estimates of embryo quality

Two systems for measuring embryo development in vitro were evaluated. One was a 1–4 scale based on a subjective evaluation of embryo quality (EQ) from microscopic appearance. In addition, a formula for scoring embryo growth rate in vitro was developed. The embryo development rating (EDR) was based on the ratio between the time at which embryos were observed at a particular stage after insemination and the time at which they would be expected to reach that stage in a hypothetical ideal growth rate with a cell cycle length of 11.9 hr. Using this scoring system, normally growing embryos scored 100. This approach was aimed at partially normalizing the data and allowed all embryos to be analyzed similarly regardless of the time of observation. Analysis of 1539 embryo replacements resulting in 232 clinical pregnancies showed that both EDR and embryo-quality scores were of value in predicting success, with clinical pregnancy most likely to eventuate from a combination of moderate to good EQ scores (2–4) coupled with average or above-average growth rates (EDR scores from 90 to 129). Poor-quality and very slowly or very rapidly growing embryos were underrepresented in cycles that proceeded to pregnancy. These inferences were based on all embryos transferred (mean, 2.73 per transfer cycle), and they were substantiated by an analysis of 33 pregnancies resulting from replacement of a single embryo and from 18 pregnancies in which all embryos scored the same with both systems. EQ and EDR were significantly associated with each other and together provide a valuable guide in predicting pregnancy, in selecting embryos for freezing, and in monitoring day-to-day performance in the in vitro fertilization (IVF) program.     

Development of spare human preimplantation embryos in vitro: An analysis of the correlations among gross morphology,cleavage rates,and development to the blastocyst

Following in vitro fertilization, the criteria commonly used to select human embryos for transfer are the cleavage rate and gross morphology, the contention being that those embryos which divide more rapidly and have regular, spherical blastomeres are more likely to lead to a pregnancy. In order to assess the validity of this assumption, the development in vitro of spare embryos was investigated. Eggs and embryos were cultured in Earle's balanced salt solution containing 10% heat-inactivated patient's serum, and insemination was performed at 40 hr post human chorionic gonadotropin (hCG). At 82–90 hr post hCG, up to four embryos were transferred. Any spare embryos were cultured in the same medium for up to 6 days and scored daily for cell number and morphology using a quality scale of 4-1 according to degree of fragmentation and shape of the blastomeres. Of 317 fertilized eggs, 55 (17%) developed to the fully expanded blastocyst stage. The remaining embryos ceased development at the one-cell (6; 2%), two-cell (49; 15%), fourcell (110; 35%), eight-cell (61; 19%), and cavitating morula (36; 11%) stages. The relationship between developmental arrest and gross morphology is discussed.     

Association between the number of oocytes and cumulative live birth rate: A systematic review

The available literature is controversial regarding the association between the number of oocytes retrieved and the cumulative live birth rate (CLBR). Although some authors report a continuous increase in the CLBR with the number of oocytes retrieved, others have found a plateau. A systematic review was conducted, including all eligible studies published until June 2022, to determine the optimal number of oocytes retrieved to maximize the CLBR. We found a positive association between the number of oocytes and the CLBR. However, this association varies according to patients’ age. While in patients younger than 35 years, little benefit is derived from increasing the number of oocytes above 25–30, in patients older than 35 years, the number of oocytes seems to improve the CLBR until the extreme of reproductive age is reached. In women aged 44 years or older, the CLBR will be consistently low, independent of the number of oocytes retrieved.