Simon Thornton

Retrospective analysis of outcomes after IVF using an aneuploidy risk model derived from time-lapse imaging without PGS

Time-lapse imaging of human preimplantation IVF embryos has enabled objective algorithms based on novel observations of development (morphokinetics) to be used for clinical selection of embryos. Embryo aneuploidy, a major cause of IVF failure, has been correlated with specific morphokinetic variables used previously to develop an aneuploidy risk classification model. The purpose of this study was to evaluate the effectiveness and potential impact of this model for unselected IVF patients without biopsy and preimplantation genetic screening (PGS). Embryo outcomes - no implantation, fetal heart beat (FHB) and live birth (LB) - of 88 transferred blastocysts were compared according to calculated aneuploidy risk classes (low, medium, high). A significant difference was seen for FHB (P<0.0001) and LB (P<0.01) rates between embryos classified as low and medium risk. Within the low-risk class, relative increases of 74% and 56%, compared with rates for all blastocysts, were observed for FHB and LB respectively. The area under the receiver operating characteristic curve was 0.75 for FHB and 0.74 for LB. This study demonstrates the clinical relevance of the aneuploidy risk classification model and introduces a novel, non-invasive method of embryo selection to yield higher implantation and live birth rates without PGS.

Children born after intracytoplasmic sperm injection: population control study

Intracytoplasmic sperm injection is often successful for treatment of male infertility; over 20 000 children have been born as a result.1 This bypassing of natural barriers to sperm selection has raised concerns about the children conceived.2 We report a population control study of children born in the United Kingdom as a result of this treatment. Children between 12 and 24 months old who had been singleton births were identified from a list of couples who had received the treatment and their parents were invited to participate; 123 of 137 families (90%) agreed. Control children, conceived naturally, were recruited from associated nurseries (105/123) or were social peers of cases (18/123). Altogether, 123 children born after intracytoplasmic sperm injection (study children) and 123 control children were seen. Children were matched for social class, maternal educational level, region, sex, and race but not maternal age. Multiple births were excluded to avoid confounding factors. Primary outcome measures were developmental scoring on the Griffiths scales of mental development3 and rates of congenital abnormalities. The Griffiths scales are an objective method of assessing development which uses five subscales. All subscales …

Live birth after polar body array comparative genomic hybridization prediction of embryo ploidy—the future of IVF?

OBJECTIVE To ascertain meiotic aneuploidy of the human egg using array comparative genomic hybridization to evaluate the 23-paired chromosome copy number of first polar body as an objective prognosticator of embryo viability for embryo transfer in the same cycle. DESIGN Case report. SETTING Independent-sector IVF program. PATIENT(S) A 41-year-old woman with a history of 13 failed cycles of IVF. INTERVENTION(S) Polar body biopsy of metaphase II eggs. MAIN OUTCOME MEASURE(S) Birth. RESULT(S) Two of the nine eggs were euploid, and the resulting embryos, although morphologically inferior to sibling embryos, were selected for transfer to the uterus, resulting in the birth of a normal healthy baby. CONCLUSION(S) Selection of euploid eggs, as an objective parameter of subsequent embryo viability and with the opportunity to transfer embryos in the same cycle could maximise the opportunity for live birth after IVF even in cases with poor prognosis.

A retrospective case-control study of developmental and other outcomes in a cohort of Australian children conceived by intracytoplasmic sperm injection compared with a similar group in the United Kingdom

OBJECTIVE To investigate the possibility that children born after ICSI were at increased risk for neurodevelopmental delay. DESIGN Retrospective case-control study. SETTING IVF clinic. PATIENT(S) Fifty-eight singleton children born after ICSI and 38 normally conceived singleton children (controls), matched for relevant sociodemographic characteristics, from Australia and 208 case-patients and 221 controls from the United Kingdom. MAIN OUTCOME MEASURE(S) Antenatal and perinatal, and sociodemographic characteristics; physical health, including congenital abnormalities; and neurodevelopment by using the Griffiths scales of mental development. RESULT(S) Eighty-five percent of case-patients and 96% controls were assessed at a mean age of 13 months. Neurodevelopmental scores were similar in all children. Perinatal outcome was similar, apart from more caesarean sections in the case-patients. Rates of congenital anomalies were similar (5.6% among case-patients vs. 5.7% among controls). Children from fathers with oligozoospermia showed no extra problems. Children born after ICSI in the United Kingdom and Australia were similar. CONCLUSION(S) Children conceived after ICSI did not differ from their naturally conceived peers in physical health or development at ages up to 15 months.

Thyroid autoimmunity and its association with cellular and humoral immunity in women with reproductive failures.

Citation Kim NY, Cho HJ, Kim HY, Yang KM, Ahn HK, Thornton S, Park JC, Beaman K, Gilman‐Sachs A, Kwak‐Kim J. Thyroid autoimmunity and its association with cellular and humoral immunity in women with reproductive failures. Am J Reprod Immunol 2011; 65: 78–87

Severe ovarian hyperstimulation syndrome: is it really preventable by prophylactic intravenous albumin?

OBJECTIVE To evaluate the effectiveness of i.v. albumin in preventing severe ovarian hyperstimulation syndrome (OHSS) in patients at risk. DESIGN Retrospective review and data analysis. SETTING University-based tertiary referral center for assisted reproductive technologies (ART). PATIENT(S) Sixty women at high risk of developing severe OHSS after superovulation for ART. INTERVENTION(S) One liter of albumin (4.5%) administered i.v. during oocyte retrieval and immediately afterward. RESULT(S) Of the 60 women who had prophylactic i.v. albumin, 5 (8%) developed severe OHSS, which led to hospitalization. Eight (13%) developed moderate OHSS. Forty-seven (78%) did not develop any symptoms. Four of the 5 women who developed severe OHSS had ET and 3 of them (75%) were pregnant (1 twin and 2 singletons). CONCLUSION(S) Intravenous albumin administered at oocyte retrieval does not prevent the occurrence of severe OHSS, especially in cases associated with pregnancy. It is important that clinicians are not lured into a false sense of security by the early report, full of promise, on the use of i.v. albumin to prevent severe OHSS.

Computer image sperm selection as a novel approach to subzonal insemination in the human

Utilizing real-time computer image analysis, individual spermatozoa were selected using microaspiration. Selection criteria were based on potential hyperactivation motility characteristics; the amplitude of lateral head displacement > 7.5 microns, curvilinear velocity > 70 microns/s and linearity of < 30%. For this pilot study, 16 patients (eight in each group) were recruited. Using subzonal insemination (SUZI), up to five (mean = 4.4 +/- 0.3) spermatozoa selected using computer-image sperm selection (CISS) were micro-injected, or up to 15 (mean = 12.8 +/- 1.3 SD) unselected spermatozoa. In the group which utilized CISS, 28 out of 49 (57%) oocytes were fertilized compared with 13 out of 52 (25%) utilizing conventional SUZI (P < 0.04); polyspermy was 20% (n = 10) and 2% (n = 1) respectively. CISS with SUZI showed increased efficiency in achieving fertilization and is a novel approach to studying individual sperm function in a sperm egg bioassay where gamete ratios are close to unity.

Low Plasma Levels of hCG After 10,000-IU hCG Injection Do Not Reduce the Number or Maturation of Oocytes Recovered in Patients Undergoing Assisted Reproduction

Purpose:Our purpose was to determine whether there is a correlation between human chorionic gonadotropin (hCG) blood levels and oocyte maturation.Methods:Three samples of blood were obtained at different times from hCG administration as follows: 12 hr, 36 hr, during oocyte recovery, and at 84 hr, when the patient comes for embryo transfer.Results:A total of 5036 oocytes was retrieved from 404 patients prospectively recruited between April 1996 and March 1997. The percentage of metaphase-II oocytes at different blood levels ranged from 84 to 88%. The general trend does not show any significant increase in percentage of metaphase-II oocytes in association with an increasing serum hCG concentration.Conclusions:The results of this study suggest that at 12, 36, and 84 hr after hCG administration, levels as low as 50, 45, and 9 IU/L of hCG, respectively, are equally potent as higher levels at initiating maximal oocyte maturity.

Assisted Reproduction Techniques for Managing Infertility

Artificial Insemination using donor sperm (AID or DI) This treatment is offered to couples where the male partner is azoospermic and involves the placement of donor sperm at the cervix or of washed donor sperm directly into the uterine cavity. Donor sperm can also be used if there is a serious risk of the male partner passing on an inherited disorder. The procedure is continued for several months and up to 50% of couples attending for DI can be successful after 6 months of treatment. Donor insemination requires careful consideration and couples are offered counselling to discuss all the implications of treatment detailed in the Code of Practice of the Human Fertilisation and Embryology Authority (HFEA). In accordance with the guidelines of the 32%

A new era of PGS for IVF - will it yield the anticipated improved efficiency?

At the outset it is necessary to establish the acronyms that geographically have a different meaning. In the UK and elsewhere it is customary to separate out the screening of chromosomes (Preimplantation Genetic Screening - PGS) from diagnosing a single gene disorder - Preimplantation Genetic Diagnosis (PGD). In some regions, notably the US, both processes PGS and PGD are often included in the over-arching term, PGD. This short article deals only with PGS (perhaps better described as Chromosome Screening). However, it should be noted that with some platforms it is becoming increasingly easier to deliver information on not only the full complement of chromosome information, including a translocation, but also the diagnosis of a monogenic diseased state as well as HLA matching, from a single cell [1] - an exciting prospect indeed.