Comprehensive analysis of early pregnancy loss based on cytogenetic findings from a tertiary referral center

Background Pregnancy loss is one of the most common complications during pregnancy. Clinical consultation based on etiology analysis are critical for reducing anxiety and distress. This study aimed to perform a comprehensive analysis for products of conception (POC) in miscarriage based on genetic etiology and clinical information. Methods A retrospective study was conducted according to cytogenetic findings of 1252 POC from spontaneous pregnancy loss over 11 years. The frequencies and profiles of chromosomal abnormalities were discussed according to the classification of women with different maternal ages, previous miscarriage history, normal live birth history, and different modes of conception. Results A total of 667 (53.2%) chromosomal abnormalities were observed, including 592 (47.3%) cases of numerical abnormalities, 38 (3.0%) cases of structural abnormalities, and 37 (3.0%) cases of mosaic aberrations. In women above 40 years of age, the rates of chromosomal abnormalities and viable autosomal trisomy were significantly higher than those in women with ≤ 29, 30–34, and 35–39 years of age (p < 0.05). The frequency of abnormal karyotype in women with normal live birth history was 61.1%, significantly higher than 52.5% in women without normal live birth history (p < 0.05). There was no significant differences among women without, with 1–2, and ≥ 3 previous miscarriages regarding the rate of abnormal karyotype (p > 0.05); viable autosomal trisomy was less common in women with ≥ 3 previous miscarriages than women with < 3 miscarriages. The frequency of chromosomal abnormalities was 49.0% and 55.0% in women with assisted conception and natural conception (p > 0.05), respectively; monosomy X was more frequently detected in women with natural conception than assisted conception. Conclusion The frequencies and profiles of chromosomal abnormalities in early miscarriages are strongly associated with clinical information including maternal age, previous miscarriage, live birth history, and mode of conception. Cytogenetic analysis of POC should be recommended to women with a first miscarriage and women with normal live birth history.

Analysis of parental abnormal chromosomal karyotype and subsequent live births in Chinese couples with recurrent pregnancy loss

The frequency and distribution of chromosomal abnormalities and the impact of parental chromosomal aberration on the pregnancy outcomes of couples with recurrent pregnancy loss remains controversial. 3235 RPL couples who experienced two or more miscarriages before 20 weeks were diagnosed in our tertiary referral hospital during 2008–2018 and included in the single-center retrospective cohort study covering a 10-year period. Chromosome aberration was detected in 121 (3.74%) among 3235 RPL couples which included 75 female and 46 male cases at an individual level. 101 cases were structural aberrations including balanced translocations in 46(38.0%) cases, Robertsonian translocations in 13(10.7%) cases, inversions in 42(34.7%) cases and 20(16.5%) cases were numerical aberrations. 121 carriers and 428 non-carriers were followed up for two years, 55 carriers and 229 non-carriers were subsequent pregnant after diagnosis by natural conception or intrauterine insemination. The frequency of carriers to have a health newborn was not significantly different with non-carriers (72.7% vs. 71.2%, adjusted P = 0.968). This study described the majority of carriers were balanced translocations and chromosome aberrations had a limited influence on live birth rate from the present data. The results of the study also remind us that natural conception may be also a good alternative rather than PGD (Pre-implantation Genetic Diagnosis) which is common in many other reproductive centers for such patients.

The Value of Anti-Müllerian Hormone in the Prediction of Spontaneous Pregnancy: A Systematic Review and Meta-Analysis

ObjectiveTo determine whether serum anti-Müllerian hormone (AMH) level is a predictor of clinical pregnancy in women trying to achieve a natural conception.MethodsThe PubMed, Embase, and Cochrane Library databases were searched for articles published until August 2020. Studies that met the inclusion and exclusion criteria were included in the meta-analysis; no language limitations were imposed. Quality was appraised using the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. Heterogeneity due to the threshold effect was identified; thus, we plotted a summary receiver operating characteristic curve and calculated its area under the summary receiver operating characteristic curve (AUC) and Cochran’s Q index to assess whether AMH level is a predictor of spontaneous pregnancy. Publication bias and sensitivity were also assessed.ResultsEleven studies (4,388 women) were ultimately included in this meta-analysis. The AUC and Cochran’s Q indices were 0.5932 and 0.5702, respectively. For women younger than 35 years, the AUC was 0.6355 and the Q index was 0.6025. For those older than 35 years, the AUC was 0.5536 and the Q index was 0.5403. Subgroup analyses by study type and population characteristics showed results similar to the overall outcome. No publication bias was identified, and the sensitivity analysis confirmed the robustness of the final result.ConclusionsSerum AMH levels have poor predictive value for natural pregnancy. The predictive value of AMH was poor in the younger and older subgroups. Our findings suggest that low serum AMH levels are not associated with reduced fertility.IntroductionThis study investigated the predictive value of anti-Müllerian hormone (AMH) level for natural pregnancy. Other than age, few factors can predict the chances of natural fertility. AMH is an established biomarker of ovarian reserve that is widely used to predict oocyte yield in cases of in vitro fertilization (IVF) and menopause. In clinical practice, the applications of AMH are increasing. However, its predictive value for natural conception remains controversial. In this study, since AMH is closely related with ovarian reserve, we evaluated whether it has predictive value for natural pregnancy. Our findings will fine-tune the clinical application of AMH in pre-pregnancy counseling. The topic should be of wide interest to investigators in the reproductive endocrinology and gynecology fields.Systematic Review RegistrationPROSPERO 2020 CRD42020216265, Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020216265.

Preimplantation genetic testing for BRCA gene mutation carriers: a cost effectiveness analysis

Background Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. Methods Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs’). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. Results IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. Conclusions IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers.

Anxiety and depression-like behaviours are more frequent in aged male mice conceived by ART compared with natural conception

The number of children born after assisted reproductive technology (ART) are accumulating rapidly and the healthy problems of the children are extensively concerned. This study aims to evaluate whether the ART procedures alter behaviours in male offspring. Mouse models were utilized to establish three groups of offspring conceived by natural conception (NC), in vitro fertilization and embryo transfer (IVF-ET) and frozen-thawed embryo transfer (IVF-FET), respectively. A battery of behaviour experiments for evaluating anxiety and depression levels, including the open field test (OFT), elevated plus maze (EPM) test, light/dark transition test (L/DTT), tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). Aged (18 months old), but not young (3 months old) male offspring, in the IVF-ET and IVF-FET groups, compared with these in the NC group, exhibited increased anxiety and depression-like behaviours. The protein expression levels of three neurotrophins in PFC or hippocampus in aged male offspring from the IVF-ET and IVF-FET groups reduced at different extent, in comparison to NC group. RNA Sequencing (RNA-Seq) was performed in the hippocampus of 18 months old offspring to further explore the gene expression profile changes in the three groups. KEGG analyses revealed the coexisted pathways, such as PI3K-Akt signalling pathway, which potentially reflected the similarity and divergence in anxiety and depression between the offspring conceived by IVF-ET and IVF-FET. Our research suggested the adverse effects of advanced age on the psychological health of children born after ART should be highlighted in future.

Comprehensive analysis of early pregnancy loss based on cytogenetic findings from a tertiary referral center

Background Pregnancy loss is one of the most common complications during pregnancy. Clinical consultation and comprehensive understanding of the etiology are critical for reducing anxiety, distress, and depression. This study aimed to perform a comprehensive analysis for products of conception (POC) in miscarriage based on genetic etiology and clinical information. Methods Retrospective observation was performed on cytogenetic findings of 1252 POC form spontaneous pregnancy loss over an 11-year period. The frequencies and profiles of chromosomal abnormalities were discussed according to the classification of women with different maternal age, previous miscarriage history, normal live birth history, and different mode of conception. Results A total of 667 (53.2%) chromosomal abnormalities were observed, including 597 (47.7%) cases of numerical abnormalities, 33 (2.6%) cases of unbalanced structural abnormalities, 32 (2.6%) cases of mosaicism, and 5 (0.4%) cases of balanced rearrangement. In group of women above 40 years of age, the detection rates of chromosomal abnormalities and viable autosomal trisomy were significantly higher than those in groups of ≤ 29, 30 ~ 34, 35 ~ 39 years of age (p < 0.05). The detection rate of abnormal karyotype in women with normal live birth history was 61.1%, significantly higher than 52.5% in women without normal live birth history (p < 0.05). There was no significant difference among women without, with 1–2, and ≥ 3 previous miscarriages in the rate of abnormal karyotype (p > 0.05), and viable autosomal trisomy was less common in women with ≥ 3 previous miscarriages. The frequency of chromosomal abnormalities was 49.0% and 41.0% in women with assisted conception and natural conception (p > 0.05), respectively, and monosomy X was more frequently detected in women with natural conception. Conclusion The frequencies and profiles of chromosomal abnormalities in early miscarriages are strongly associated with clinical information including the maternal age, previous miscarriage, live birth history, and mode of conception. Even in women with a first miscarriage, or with a history of normal live births, chromosomal analysis of POC should be recommended for etiological assessment.

Preconception leukocyte telomere length and pregnancy outcomes among women with demonstrated fecundity

STUDY QUESTION Is preconception leukocyte telomere length associated with fecundability, pregnancy loss and live birth among women attempting natural conception with a history of 1–2 prior pregnancy losses? SUMMARY ANSWER Preconception leukocyte telomere length is not associated with fecundability, pregnancy loss or live birth. WHAT IS KNOWN ALREADY As women increasingly delay childbearing, accessible preconception biomarkers to predict pregnancy outcomes among women seeking natural conception could improve preconception counseling. Findings of small case–control or cross-sectional studies suggest that telomere attrition is associated with adverse pregnancy outcomes among women undergoing fertility treatment, but prospective studies in non-clinical populations are lacking. STUDY DESIGN, SIZE, DURATION Participants included 1228 women aged 18–40 years with a history of 1–2 prior pregnancy losses who were recruited at four university medical centers (2006–2012). PARTICIPANTS/MATERIALS, SETTING, METHODS Preconception leukocyte telomere length was measured at baseline using PCR and reported as a ratio (T/S) in relation to population-specific standard reference DNA. Women were followed for up to six cycles while attempting to conceive. Associations of telomere length with fecundability, live birth and pregnancy loss were estimated using discrete Cox proportional hazards models and log-binomial models. MAIN RESULTS AND THE ROLE OF CHANCE After adjustment for age, BMI, smoking and other factors, preconception telomere length was not associated with fecundability (Q4 vs Q1 FOR = 1.00; 95% CI = 0.79, 1.27), live birth (Q4 vs Q1 RR = 1.00; 95% CI = 0.85, 1.19), or pregnancy loss (Q4 vs Q1 RR = 1.12; 95% CI = 0.78, 1.62). LIMITATIONS, REASONS FOR CAUTION Telomere length was measured in leukocytes, which is an accessible tissue in women attempting natural conception but may not reflect telomere length in oocytes. Most women were younger than 35 years, limiting our ability to evaluate associations among older women. Participants had a history of 1–2 prior pregnancy losses; therefore, our findings may not be widely generalizable. WIDER IMPLICATIONS OF THE FINDINGS Despite prior research suggesting that telomere length may be associated with pregnancy outcomes among women seeking fertility treatment, our findings suggest that leukocyte telomere length is not a suitable biomarker of pregnancy establishment or maintenance among women attempting natural conception. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (National Institutes of Health, Bethesda, MD, USA; contract numbers HHSN267200603423, HHSN267200603424 and HHSN267200603426). The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER The trial was registered with ClinicalTrials.gov, number NCT00467363.

Fertility Preservation Programme in a Tertiary-Assisted Reproduction Unit in Hong Kong

Background: Fertility preservation is increasingly important with improving cancer survival rates and the delay in childbearing in modern societies. The objective of our study was to review the experience of the fertility preservation programme in a tertiary-assisted reproduction unit in Hong Kong. Methods: This is a retrospective study involving men and women who were seen at a tertiary-assisted reproduction unit for fertility preservation counselling before gonadotoxic treatment from January 2005 to December 2020. Their medical records in paper and electronic forms were reviewed. Results: There were 75 consultations for female fertility preservation from 2010 to 2020 involving 72 women. Twenty women underwent 22 cycles of ovarian stimulation for oocyte or embryo cryopreservation, two of whom subsequently transported their oocytes abroad for further management and another two achieved natural conception. Additional four women who did not have oocyte or embryo cryopreservation achieved natural conception after cancer treatment. Eleven (15.2%) women were followed up at a reproductive endocrinology clinic after their cancer treatment. From 2005 to 2020, 265 men had sperm cryopreserved. Twenty-six (9.8%) came back to use the cryopreserved sperms, the wives of 13 (50.0%) of whom achieved an on-going pregnancy. Six of them transferred out and 40 discarded the cryopreserved sperms. Conclusions: There was generally an increasing number of patient consultations for fertility preservation in our Centre over the past decade but a consistently low rate of utilisation of cryopreserved gametes for both women and men. Post-cancer treatment fertility evaluation and monitoring was a major area of deficiency in Hong Kong. More structured post-cancer treatment fertility follow-up is needed.