Simon Fishel

Modelling a risk classification of aneuploidy in human embryos using non-invasive morphokinetics

This study determined whether morphokinetic variables between aneuploid and euploid embryos differ as a potential aid to select euploid embryos for transfer. Following insemination, EmbryoScope time-lapse images from 98 blastocysts were collected and analysed blinded to ploidy. The morphokinetic variables were retrospectively compared with ploidy, which was determined following trophectoderm biopsy and analysis by array comparative genomic hybridization or single-nucleotide polymorphic array. Multiple aneuploid embryos were delayed at the initiation of compaction (tSC; median 85.1 hours post insemination (hpi); P=0.02) and the time to reach full blastocyst stage (tB; median 110.9hpi, P=0.01) compared with euploid embryos (tSC median 79.7 hpi, tB median 105.9 hpi). Embryos having single or multiple aneuploidy (median 103.4 hpi, P=0.004 and 101.9 hpi, P=0.006, respectively) had delayed initiation of blastulation compared with euploid embryos (median 95.1hpi). No significant differences were observed in first or second cell-cycle length, synchrony of the second or third cell cycles, duration of blastulation, multinucleation at the 2-cell stage and irregular division patterns between euploid and aneuploid embryos. This non-invasive model for ploidy classification may be used to avoid selecting embryos with high risk of aneuploidy while selecting those with reduced risk.

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.

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.

Use of recombinant FSH and recombinant LH in multiple follicular stimulation for IVF: a preliminary study

Twelve patients (17 cycles) who needed >3000 IU of recombinant FSH (rFSH) on previous follicular stimulation attempts for IVF using rFSH (group A) underwent further attempts (a total of 12 cycles) using rFSH supplemented with rLH from day 7 of stimulation (group B). There was no significant difference in the total quantitative administration of rFSH (mean: 4759 versus 4800 IU rFSH), days of stimulation (14.0 versus 12.6), number of M2 oocytes per patient (3.76 versus 4.17) or embryo morphology between group A and group B respectively. However, there was a significant increase in the incidence of fertilization (60.9 versus 86.0%; P = 0.006) and clinical (ongoing) pregnancies (1 versus 6; P = 0.022). The higher incidence of fertilization increased the mean number of embryos transferred per patient, although in this small group the data was not significant (1.75 versus 2.71). This preliminary clinical trial suggests that in poor responders superimposing rLH upon a down-regulated cycle stimulated with rFSH improves relevant outcome data; and this preliminary trial has encouraged the need for a larger and more detailed study.

γ-Aminobutyric acid (GABA) a and b receptors mediate the stimulatory effects of GABA on the human sperm acrosome reaction: interaction with progesterone

OBJECTIVE To evaluate which gamma-aminobutyric acid (GABA) receptor mediates the stimulatory effects of this neurotransmitter on the human sperm acrosome reaction, and to examine the interaction of progesterone, a physiologic inducer of the acrosome reaction, with the GABA(A) receptor. DESIGN Prospective study. SETTING A university clinic of andrology. PATIENT(S) Men with normal sperm analysis parameters. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) The acrosome reaction of motile spermatozoa. RESULT(S) The acrosome reaction was stimulated by GABA in a dose-dependent manner. This effect was inhibited completely by bicuculline, a GABA(A) receptor antagonist, and only partially by saclofen, a GABA(B) receptor antagonist. Accordingly, muscimol, a GABA(A) receptor agonist, stimulated the acrosome reaction to the same extent as GABA, whereas baclofen, a GABA(B) receptor agonist, was less effective. Preincubation with progesterone followed by the addition of GABA resulted in a significant increase in the percentage of acrosome-reacted spermatozoa compared with progesterone alone. However, this increase was less than a simple addition of effects, suggesting that GABA and progesterone act through the same receptor and/or use the same mechanism of action. To test this hypothesis, the ability of progesterone to induce acrosome reaction was tested in the presence of bicuculline, which suppressed the stimulatory effects of progesterone. Given that the GABA(A) receptor is linked to the chloride channel, we tested whether picrotoxin, a blocker of this channel, could modulate the effects of progesterone or GABA. Picrotoxin completely suppressed the acrosome reaction induced by progesterone and only partially suppressed that caused by GABA. CONCLUSION(S) gamma-Aminobutyric acid stimulated the acrosome reaction in human spermatozoa, acting mainly through the GABA(A) receptor and to a lesser extent through the GABA(B) receptor. Progesterone interacted with the GABA(A) receptor to induce the acrosome reaction, and the functional integrity of the chloride channel was vital for this effect.

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.

General anesthesia for intrauterine placement of human conceptuses after in vitro fertilization

General anesthesia has been used for the replacement of human conceptuses after in vitro fertilization (IVF). Two adjuvants, enflurane and halothane, have been compared. Halothane significantly reduced the incidence of implantation compared to enflurane. In 356 replacements, the incidence of implantation for enflurane and halothane was 34 and 17%, respectively (P=0.005). Sixty-four percent of all replacements had three conceptuses; the incidence of implantation for enflurane and halothane in this group was 43 and 19%, respectively (P =0.002). The incidence of multiple pregnancy was similar for both anesthetic agents (20%) and the demise of implantation sacs 5 weeks postovulation was 11% for enflurane and 12% for halothane.

Current Trends of Reproductive Immunology Practices in In Vitro fertilization (IVF) - A First World Survey Using IVF-Worldwide.com

Reproductive immunology has evolved from basic research studies to clinical applications. In this study, we aim to investigate the actual application of reproductive immunology concepts and findings in clinical reproductive medicine such as recurrent pregnancy losses (RPL), repeated implantation failures (RIF), and failed in vitro fertilization (IVF) cycles.

Evaluation of high vaginal insemination at oocyte recovery in patients undergoing in vitro fertilization

The value of high vaginal insemination at the time of oocyte recovery for in vitro fertilization (IVF) has been assessed. A previous study reported a dramatic increase in the incidence of pregnancy in women after high vaginal insemination (53%) compared with those without insemination (23%). Of 306 patients undergoing IVF, 97 (32%) became pregnant and 20 (21%) miscarried. Those patients with tubal damage numbered 187. Sixty (33%) became pregnant and 10 (17%) miscarried. The data were assessed according to the numbers of conceptuses replaced, the age of the patient, and whether a spontaneous luteinzing hormone surge or human chorionic gonadotropin was a trigger for ovulation, each with a significant effect on the outcome of treatment. No significant effect of the use of high vaginal insemination was found.

Comparison of second trimester biometry in singleton and twin pregnancies conceived with assisted reproductive techniques.

The objective of this study was to investigate the size of singleton vs twin pregnancies at the time of a second trimester dating scan. The analysis included 86 infants from 63 pregnancies achieved with assisted reproductive techniques, comprising 40 singletons and 46 twins. Measurements of second trimester biparietal diameter (n= 85) and femur length (n= 74) were plotted against the precisely known gestational age. A common regression line was calculated for each parameter and the residuals for singletons and twins were compared. Gestational age and weight at birth were also analysed for each group. There was no significant difference between singletons and twins in biparietal diameter or femur length in second trimester. In contrast, twins had a lower mean birthweight, gestational age at birth, and weight‐for‐gestational age centile compared with singletons. Singleton babies from these pregnancies had an average birthweight centile of 49.8% (i.e. close to the median for spontaneously conceived pregnancies in our population). We concluded that the same pregnancy dating charts can be used for singletons and twins. At corresponding gestational age, twins are smaller than singletons at birth because of slower growth in the third trimester.