Chromosomal polymorphisms in assisted reproduction: an analysis of 942 cycles.

The use of intracytoplasmic sperm injection (ICSI) has recently increased worldwide. The live birth rate per ICSI cycle is low, and over half of infertile couples remain childless. Chromosomal polymorphisms are up to five times more common in couples with infertility compared to the general population. We aimed to investigate the association between chromosomal polymorphisms and reproductive outcomes in couples undergoing ICSI treatment. We analysed 942 ICSI fresh and frozen embryo transfer cycles in 697 women who underwent karyotyping analysis using Giemsa-Trypsin-Leishman banding prior to assisted conception at the Fertility Centre of Lanka Hospitals, Sri Lanka, between 2016 and 2018. The primary outcomes were pregnancy, miscarriage, and live birth rates. We compared outcomes according to the presence or absence of chromosomal polymorphism in females, males and couples. There were 294 pregnancies (31.2%) recorded in the study; 130 suffered a miscarriage (13.8%), 13 were ectopic pregnancies (1.3%) and 151 resulted in a live birth (16.0%). The evidence from univariable and multivariable analyses (adjusted for age, BMI, ovarian reserve and treatment type) did not confidently identify a difference in pregnancy, miscarriage or live birth rates between couples with no chromosomal polymorphisms compared to couples where the female, male or both partners were carriers of a chromosomal polymorphism. Further, we did not identify a clear association between the presence of chromosomal polymorphisms and reproductive outcomes compared to participants without chromosomal polymorphisms. Wide CIs precluded the identification of clinically meaningful associations. Infertility affects approximately one in eight couples worldwide. The use of intracytoplasmic sperm injection (ICSI), where the sperm is directly injected into an egg using a micromanipulator outside the body, has become particularly popular in recent years. However, the success rate remains low. In human cells, the genetic material is arranged in structures called chromosomes. Chromosomal polymorphism is a normal variation where the genetic material is arranged differently to the average individual and is more common in infertile couples compared to the general population. We analysed data from 942 ICSI cycles in 697 couples who underwent karyotyping analysis to assess the changes in chromosomes between 2016 and 2018. The pregnancy rate was 31.2%, with 16.0% of participants experiencing a live birth, while 13.8% of pregnancies resulted in a miscarriage and 1.3% were outside the womb cavity (ectopic). The evidence did not identify a clear association between the chromosomal polymorphism and the outcome of treatment.

Ralapanawe MSB ，Gajaweera SL ，Karunaratne N ，Price MJ ，Melo P ，Coomarasamy A ，Gallos I ... -  《-》

A comprehensive analysis of chromosomal polymorphic variants on reproductive outcomes after intracytoplasmic sperm injection treatment.

Recent studies suggest that chromosomal polymorphic variations are associated with infertility. A systematic review of chromosomal polymorphisms in assisted reproduction found an association with higher rates of miscarriage. Aim of this study is to analyse the influence of specific types or number of chromosomal polymorphic variations on reproductive outcomes of couples undergoing ICSI treatment. We analysed data from 929 fresh and frozen embryo transfer cycles of 692 women who underwent karyotyping analysis using Giemsa-Trypsin-Leishman (GTL) banding prior to the ICSI procedure at the Fertility Centre of Lanka Hospitals Corporation Plc, Sri Lanka, from January 2016 to December 2018. The outcomes of interest were the pregnancy, miscarriage and live birth rate per cycle. There was no evidence of a difference in the reproductive outcomes between carriers or non-carriers of any type or number of chromosomal polymorphic variation. Our data, in contrast to previous studies, does not support a deleterious effect for the type or number of chromosomal polymorphic variations on reproductive outcomes. However, additional prospective, adequately powered studies, conducted in multiethnic populations, are required to further investigate whether the detection of chromosomal polymorphic variants prior to assisted conception may in fact be a futile diagnostic tool.

Ralapanawe MSB ，Gajaweera SL ，Karunaratne N ，Dissanayake VHW ，Price MJ ，Melo P ，Coomarasamy A ，Gallos ID ... -  《Scientific Reports》

In vitro fertilization and multiple pregnancies: an evidence-based analysis.

Medical Advisory Secretariat 《-》

Cumulative live birth rates following miscarriage in an initial complete cycle of IVF: a retrospective cohort study of 112 549 women.

In women undergoing IVF/ICSI who miscarry in their first complete cycle, what is the chance of a live birth in subsequent complete cycles, and how does this compare with those whose first complete cycle ends with live birth or without a pregnancy? After two further complete cycles of IVF/ICSI, women who had miscarried or had a live birth in their first complete cycle had a higher chance of live birth (40.9 and 49.0%, respectively) than those who had no pregnancies (30.1%). Cumulative live birth rates (CLBRs) after one or more complete cycles of IVF have been reported previously, as have some of the risk factors associated with miscarriage, both in general populations and in those undergoing IVF. Chances of cumulative live birth after a number of complete IVF cycles involving replacement of fresh followed by frozen embryos after an initial miscarriage in a population undergoing IVF treatment have not been reported previously. National population-based cohort study of 112 549 women who started their first IVF treatment between 1999 and 2008. Data from the UK Human Fertilisation and Embryology Authority (HFEA) register on IVF/ICSI treatments, using autologous gametes were analysed. CLBRs were estimated in women who (i) had miscarriage (and no live birth), (ii) at least one live birth or (iii) no pregnancy in their first complete cycle of IVF/ICSI (including fresh and frozen embryo transfers following a single oocyte retrieval episode). A multivariable analysis was performed to assess the effect of first complete cycle outcome on subsequent CLBRs after adjusting for confounding factors such as female age, duration of infertility and cause of infertility. In their first complete cycle, 9321 (8.3%) women had at least one miscarriage (and no live birth); 33 152 (29.5%) had at least one live birth and 70 076 (62.3%) had no pregnancies. After two further complete cycles, conservative CLBRs (which assume that women who discontinued treatment subsequently never had a live birth) were 40.9, 49.0 and 30.1%, while optimal CLBRs (which assume that women who discontinue have the same chance of live birth as those treated) were 49.5, 57.9 and 38.4% in the miscarriage, live birth and no pregnancy groups respectively. Odds of cumulative live birth for women who miscarried in their first complete cycle were 42% higher than those who had no pregnancy [odds ratio (95% CI) = 1.42 (1.34, 1.50)], and twice as high for live birth versus no pregnancy [2.04 (1.89, 2.20)]. Negative predictors for live birth in all women included tubal infertility [0.88 (0.82, 0.94)] and increasing age [18-40 years = 0.94 (0.94, 0.95); >40 years = 0.63 (0.59, 0.66) per year]. CLBRs could not be estimated for treatments occurring after September 2008 due to potentially incomplete data following regulatory changes regarding consent for data use in research. Additionally, covariates not included in the HFEA database (including BMI, smoking, previous history of miscarriage and gestational age at miscarriage) could not be adjusted for in our analysis. Miscarriage following IVF can be devastating for couples who are uncertain about their ultimate prognosis. Our findings will provide reassurance to these couples as they consider their options for continuing treatment. N.J.C. received an Aberdeen Summer Research Scholarship funded by the Institute of Applied Health Sciences (University of Aberdeen), through the Aberdeen Clinical Academic Training Scheme. This work was supported by a Chief Scientist Office Postdoctoral Training Fellowship in Health Services Research and Health of the Public Research (Ref PDF/12/06). The views expressed here are those of the authors and not necessarily those of the Chief Scientist Office or the University of Aberdeen. The funders did not have any role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; nor in the decision to submit the paper for publication. None of the authors has any conflicts of interest to declare.

Cameron NJ ，Bhattacharya S ，Bhattacharya S ，McLernon DJ ... -  《-》

Association between gestational trophoblastic disease (GTD) history and clinical outcomes in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles.

Gestational trophoblastic disease (GTD) usually affects young women of childbearing age. After treatment for GTD, 86% of women wish to achieve pregnancy. On account of the impacts of GTD and treatments as well as patient anxiety, large numbers of couples turn to assisted reproductive technology (ART), especially in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). But few studies have investigated whether a history of GTD affects the outcomes of IVF/ICSI in secondary infertile patients and how it occurs. We investigate whether a history of GTD affects the IVF/ICSI outcomes and the live birth rates in women with secondary infertility. This retrospective cohort study enrolled 176 women with secondary infertility who underwent IVF/ICSI treatment at the reproductive medical center of Nanjing Drum Tower Hospital from January 1, 2016, to December 31, 2020. Participants were divided into the GTD group (44 women with GTD history) and control group (132 women without GTD history matched from 8318 secondary infertile women). The control group and the study group were matched at a ratio of 3:1 according to patient age, infertility duration, number of cycles and body mass index (BMI). We assessed retrieved oocytes and high-grade embryos, biochemical pregnancy, miscarriage, ectopic pregnancy, gestational age at delivery, delivery mode and live birth rates. We found a significantly reduced live-birth rate (34.1% vs 66.7%) associated with IVF/ICSI cycles in patients with a GTD history compared to those without a GTD history. The biochemical pregnancy and miscarriage rates of the GTD group were slightly higher than those of the control group. In addition, there was a difference in gestational age at delivery between the GTD and control groups (p < 0.001) but no differences in the mode of delivery (p = 0.267). Furthermore, the number of abandoned embryos in the GTD group was greater than that in the control group (p = 0.018), and the number of good-quality embryos was less than that in the control group (p = 0.019). The endometrial thickness was thinner (p < 0.001) in the GTD group. Immunohistochemistry (IHC) showed abnormal endometrial receptivity in the GTD group. The GTD history of patients undergoing IVF/ICSI cycles had an impact on the live-birth rate and gestational age at delivery, which might result from the thinner endometrium and abnormal endometrial receptivity before embryo transfer.

Cai X ，Zhang M ，Huang C ，Jiang Y ，Zhou J ，Xu M ，Yan G ，Sun H ，Kong N ... -  《Reproductive Biology and Endocrinology》