Estella Yl Lau

Live birth rate, multiple pregnancy rate, and obstetric outcomes of elective single and double embryo transfers: Hong Kong experience.

OBJECTIVE To compare the live birth rate, multiple pregnancy rate, and obstetric outcomes of elective single and double embryo transfers. DESIGN Case series with internal comparisons. SETTING University affiliated hospital, Hong Kong. PARTICIPANTS Between October 2009 and December 2011, 206 women underwent their first in-vitro fertilisation cycle. Elective single embryo transfer was offered to women who were aged 35 years or below, and had endometrial thickness of 8 mm or more and at least two embryos of good quality. MAIN OUTCOME MEASURES Live birth rate, multiple birth rate, and obstetric outcomes. RESULTS Among the 206 eligible women, 74 underwent an elective single embryo transfer and 132 a double embryo transfer. The live birth rate was comparable in the two groups, being 39.2% in the elective single embryo transfer group and 43.2% in the double embryo transfer group, while the multiple pregnancy rate was significantly lower in the elective single embryo transfer group than the double embryo transfer group (6.9% vs 40.4%; P<0.001). Gestational ages and birth weights were comparable in the two groups. There was no significant difference between the two groups with respect to the rate of preterm delivery and antenatal complications (27.6% vs 43.9%, respectively; P>0.05). CONCLUSION In this selected population, an elective single embryo transfer policy decreases the multiple pregnancy rate without compromising the live birth rate. The non-significant difference in antenatal complications may be related to the small sample size.

Role of baseline antral follicle count and anti-Mullerian hormone in the index stimulation cycle of IVF treatment in predicting outcome of subsequent frozen-thawed embryo transfers

Abstract This retrospective cohort study aims at determining whether baseline antral follicle count (AFC) and serum anti-Mullerian hormone (AMH) level in the index stimulation cycle predict live-birth outcome in subsequent frozen-thawed embryo transfer (FET) cycles. We studied 500 women undergoing the first IVF cycle who had embryo(s) cryopreserved. The main outcome measures were live-birth in the first FET cycle and cumulative live-birth in all the FETs combined after the same stimulation cycle. Our results showed that baseline AFC and AMH level on the day before ovarian stimulation showed significant correlation. In the first FET cycle, AFC and AMH level were significantly higher in subjects attaining live-birth in the first FET cycle or cumulative live-birth from all FETs than those who did not. Both AMH and AFC were insignificant predictors of live-birth in the first FET cycle or cumulative live-birth after adjusting for age. The areas under the ROC curves for AMH, AFC and age were 0.654, 0.625 and 0.628, respectively, for predicting cumulative live-birth. In conclusion, we reported for the first time that baseline AFC and AMH in the index stimulation cycle have only modest predictive performance on cumulative live-birth in subsequent FET cycles.

Preimplantation genetic diagnosis and screening by array comparative genomic hybridisation: experience of more than 100 cases in a single centre

INTRODUCTION Preimplantation genetic screening has been proposed to improve the in-vitro fertilisation outcome by screening for aneuploid embryos or blastocysts. This study aimed to report the outcome of 133 cycles of preimplantation genetic diagnosis and screening by array comparative genomic hybridisation. METHODS This study of case series was conducted in a tertiary assisted reproductive centre in Hong Kong. Patients who underwent preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening between 1 April 2012 and 30 June 2015 were included. They underwent in-vitro fertilisation and intracytoplasmic sperm injection. An embryo biopsy was performed on day-3 embryos and the blastomere was subject to array comparative genomic hybridisation. Embryos with normal copy numbers were replaced. The ongoing pregnancy rate, implantation rate, and miscarriage rate were studied. RESULTS During the study period, 133 cycles of preimplantation genetic diagnosis for chromosomal abnormalities or preimplantation genetic screening were initiated in 94 patients. Overall, 112 cycles proceeded to embryo biopsy and 65 cycles had embryo transfer. The ongoing pregnancy rate per transfer cycle after preimplantation genetic screening was 50.0% and that after preimplantation genetic diagnosis was 34.9%. The implantation rates after preimplantation genetic screening and diagnosis were 45.7% and 41.1%, respectively and the miscarriage rates were 8.3% and 28.6%, respectively. There were 26 frozen-thawed embryo transfer cycles, in which vitrified and biopsied genetically transferrable embryos were replaced, resulting in an ongoing pregnancy rate of 36.4% in the screening group and 60.0% in the diagnosis group. CONCLUSIONS The clinical outcomes of preimplantation genetic diagnosis and screening using comparative genomic hybridisation in our unit were comparable to those reported internationally. Genetically transferrable embryos replaced in a natural cycle may improve the ongoing pregnancy rate and implantation rate when compared with transfer in a stimulated cycle.

Experience of more than 100 preimplantation genetic diagnosis cycles for monogenetic diseases using whole genome amplification and linkage analysis in a single centre.

OBJECTIVE To report the outcomes of more than 100 cycles of preimplantation genetic diagnosis for monogenetic diseases. DESIGN Case series. SETTING Tertiary assisted reproductive centre in Hong Kong, where patients needed to pay for the cost of preimplantation genetic diagnosis on top of standard in-vitro fertilisation charges. PATIENTS Patients undergoing preimplantation genetic diagnosis for monogenetic diseases at the Centre of Assisted Reproduction and Embryology, Queen Mary Hospital-The University of Hong Kong between 1 August 2007 and 30 April 2014 were included. INTERVENTIONS In-vitro fertilisation, intracytoplasmic sperm injection, embryo biopsy, and preimplantation genetic diagnosis. MAIN OUTCOME MEASURES Ongoing pregnancy rate and implantation rate. RESULTS Overall, 124 cycles of preimplantation genetic diagnosis were initiated in 76 patients, 101 cycles proceeded to preimplantation genetic diagnosis, and 92 cycles had embryo transfer. The ongoing pregnancy rate was 28.2% per initiated cycle and 38.0% per embryo transfer, giving an implantation rate of 35.2%. There were 16 frozen-thawed embryo transfer cycles in which, following preimplantation genetic diagnosis, cryopreserved embryos were replaced resulting in an ongoing pregnancy rate of 37.5% and implantation rate of 30.0%. The cumulative ongoing pregnancy rate was 33.1%. The most frequent indication for preimplantation genetic diagnosis was thalassaemia, followed by neurodegenerative disorder and cancer predisposition. There was no misdiagnosis. CONCLUSIONS Preimplantation genetic diagnosis is a reliable method to prevent couples conceiving fetuses severely affected by known genetic disorders, with ongoing pregnancy and implantation rates similar to those for in-vitro fertilisation for routine infertility treatment.

Live birth following double-factor pre-implantation genetic diagnosis for both reciprocal translocation and alpha- thalassaemia

We report a live birth from a couple with two genetic diseases, namely: reciprocal translocation carrier and alpha-thalassaemia trait, following pre-implantation genetic diagnostic tests. This is the first case in Hong Kong in which the technique of using one blastomere biopsy for two diseases was established, using array comparative genomic hybridisation and polymerase chain reaction.

Evaluation of preimplantation genetic testing for chromosomal structural rearrangement by a commonly used next generation sequencing workflow

OBJECTIVES To evaluate the applicability of a commonly used next generation sequencing workflow in detecting unbalanced meiotic segregation products for reciprocal translocation and inversion carriers. STUDY DESIGN All preimplantation genetic testing treatment cycles performed for reciprocal translocation or inversion carriers from 2012 to April 2017 were included. Three hundreds and forty-two archived whole genome amplified DNA, which had previously analyzed by array comparative genomic hybridization (aCGH), were retrospectively analyzed by next generation sequencing (NGS). Concordance on overall diagnosis and segmental aneuploidies related to the translocation/inversion breakpoints between aCGH and NGS were determined. RESULTS Retrospective analysis of 287 blastomere biopsies and 55 trophectoderm (TE) biopsies showed that the concordance rate on the overall diagnosis between aCGH and NGS on abnormal samples was 100% (266/266), irrespective to the type of biopsy. The concordance rates of normal biopsies were 98.4% (61/62) on blastomere and 78.6% (11/14) on TE biopsies. NGS detected a de novo segmental aneuploidy on one blastomere biopsy and three possible low level mosaic aneuploidies on 3 TE biopsies, which were previously concluded as euploid by aCGH. Using the karyotype of reciprocal translocation/inversion carriers, size of anticipated segmental aneuploidies could be calculated and be used to predict the applicability of NGS before proceeding to treatment. CONCLUSION This is the first report to evaluate the applicability of a commercial NGS-based workflow for preimplantation testing for reciprocal translocations/inversions. Our study demonstrated that NGS can diagnose unbalanced translocation/inversion products with the same efficiency as aCGH. The applicability of NGS, with respect to individual karyotype, can be predicted before proceeding to treatment.

Comparison between fluorescent in-situ hybridisation and array comparative genomic hybridisation in preimplantation genetic diagnosis in translocation carriers.

OBJECTIVES To compare the pregnancy outcome of the fluorescent in-situ hybridisation and array comparative genomic hybridisation in preimplantation genetic diagnosis of translocation carriers. DESIGN Historical cohort. SETTING A teaching hospital in Hong Kong. PATIENTS All preimplantation genetic diagnosis treatment cycles performed for translocation carriers from 2001 to 2013. RESULTS Overall, 101 treatment cycles for preimplantation genetic diagnosis in translocation were included: 77 cycles for reciprocal translocation and 24 cycles for Robertsonian translocation. Fluorescent in-situ hybridisation and array comparative genomic hybridisation were used in 78 and 11 cycles, respectively. The ongoing pregnancy rate per initiated cycle after array comparative genomic hybridisation was significantly higher than that after fluorescent in-situ hybridisation in all translocation carriers (36.4% vs 9.0%; P=0.010). The miscarriage rate was comparable with both techniques. The testing method (array comparative genomic hybridisation or fluorescent in-situ hybridisation) was the only significant factor affecting the ongoing pregnancy rate after controlling for the womens age, type of translocation, and clinical information of the preimplantation genetic diagnosis cycles by logistic regression (odds ratio=1.875; P=0.023; 95% confidence interval, 1.090-3.226). CONCLUSION This local retrospective study confirmed that comparative genomic hybridisation is associated with significantly higher pregnancy rates versus fluorescent in-situ hybridisation in translocation carriers. Array comparative genomic hybridisation should be the technique of choice in preimplantation genetic diagnosis cycles in translocation carriers.

A Prospective Randomized Control Study to Compare the Effect of Serum and a Commercial Serum Substitute (Plasmanate) on the Outcome of Assisted Reproduction Program

Objectives: To compare the effect of supplementation of serum and Plasmanate, a commercial serum substitute, to culture medium on the IVF outcome.