Peter Platteau

The influence of body weight on response to ovulation induction with gonadotrophins in 335 women with World Health Organization group II anovulatory infertility.

Objective  To assess the influence of body weight on the outcome of ovulation induction in women with World Health Organization (WHO) group II anovulatory infertility.

Live delivery rates in subfertile women with Asherman's syndrome after hysteroscopic adhesiolysis using the resectoscope or the Versapoint system

The purpose of this study was to report on a 10-year experience in the treatment of subfertile women with intrauterine adhesions using the resectoscope or the Versapoint system. Forty-six subfertile women with stage I (n = 6), stage II (n = 25) and stage III (n = 15) intrauterine adhesions underwent adhesiolysis with the use of the resectoscope (n = 21) or the Versapoint system (n = 26). Synechiolysis was successful in 43 women (93.5%) after the first attempt. In 13 out of 14 women (92.9%) with oligo/amenorrhoea at presentation, restoration of menses was reported after adhesiolysis (Versapoint: 9/9, resectoscope: 4/5). Overall live delivery rates according to stage of intrauterine adhesions were 33.3, 44.4 and 46.7% for stages I, II and III respectively. Similar cumulative delivery rates were achieved in patients with no additional infertility factors who attempted to conceive naturally after adhesiolysis using the Versapoint (71.7%) or the resectoscope (60%). Ten gestations ended in preterm delivery (50%), while in two of the women who delivered, a hysterectomy was performed due to placenta accreta. In conclusion, hysteroscopic adhesiolysis offers a real chance of parenthood in a substantial proportion of infertile couples either by using the Versapoint system or the resectoscope.

PGD in the lab for triplet repeat diseases — myotonic dystrophy, Huntington's disease and Fragile-X syndrome

Myotonic dystrophy (DM), Huntingtons disease (HD) and Fragile X syndrome (FRAXA) are three monogenic disease which are caused by so-called dynamic mutations. These mutations are caused by triplet repeats inside or in the vicinity of the gene which have the tendency to expand beyond the normal range thus disrupting the normal functioning of the gene. We describe here our experiences from 1995 to May 2000 with PGD for these three triplet repeat diseases.

Preimplantation genetic diagnosis for Huntington's disease with exclusion testing

Huntingtons disease is an autosomal dominant, late-onset disorder, for which the gene and the causative mutation have been known since 1993. Some at-risk patients choose for presymptomatic testing and can make reproductive choices accordingly. Others however, prefer not to know their carrier status, but may still wish to prevent the birth of a carrier child. For these patients, exclusion testing after prenatal sampling has been an option for many years. A disadvantage of this test is that unaffected pregnancies may be terminated if the parent at risk (50%) has not inherited the grandparental Huntington gene, leading to serious moral and ethical objections. As an alternative, preimplantation genetic diagnosis (PGD) on embryos obtained in vitro may be proposed, after which only embryos free of risk are replaced. Embryos can then be selected, either by the amplification of the CAG repeat in the embryos without communicating results to the patients (ie non-disclosure testing), which brings its own practical and moral problems, or exclusion testing. We describe here the first PGD cycles for exclusion testing for Huntingtons disease in five couples. Three couples have had at least one PGD cycle so far. One pregnancy ensued and a healthy female baby was delivered.

Clinical validation of a closed vitrification system in an oocyte-donation programme

Controversy exists about the risk of microbiological contamination from direct contact with unsterile liquid nitrogen during oocyte vitrification. The aim of this observational study was to evaluate the effectiveness of oocyte vitrification using a high-security closed vitrification system in a donation programme. Oocyte vitrification was performed using CBS High Security closed straws (Cryo Bio System) with DMSO/ethylene glycol/sucrose as the cryoprotectant (Irvine Scientific freeze kit). A total of 123 vitrified metaphase-II oocytes were warmed in 20 recipient cycles (6.2 warmed oocytes per recipient); of these, 111 oocytes (90.2%) survived vitrification and warming. All surviving oocytes were microinjected and 86 (77.5%) were normally fertilized, of which 53 (61.6%) developed up to good-quality day 3. Ten embryo transfers resulted in a clinical pregnancy (50.0%) and an ongoing clinical pregnancy rate of 45%. Five revitrified embryos were warmed in three warming cycles (survival rate 100%). These transfers resulted in an additional ongoing twin pregnancy, leading to a cumulative ongoing pregnancy rate per patient of 50% (10/20). The ongoing implantation rate per warmed oocyte and per injected oocyte was 10.6% (13/123) and 11.7% (13/111). The present data demonstrate that oocyte vitrification using a closed vitrification device yields excellent oocyte survival, fertilization and embryo development.

First live birth after ovarian stimulation using a chimeric long-acting human recombinant follicle-stimulating hormone (FSH) agonist (recFSH-CTP) for in vitro fertilization ☆

OBJECTIVE To report the first pregnancy and live birth after ovarian stimulation using a chimeric long-acting human recombinant FSH agonist (recFSH-CTP) for IVF. DESIGN Case report. SETTING Tertiary fertility center. PATIENT(S) A 32-year-old woman with a 7-year history of primary infertility. INTERVENTION(S) Ovarian stimulation with a single SC injection of 180 microg recFSH-CTP on cycle day 3, followed by daily injections of 150 IU recFSH from cycle day 10 onward, combined with daily GnRH antagonist 0.25 mg SC to prevent a premature LH rise. Final oocyte maturation was induced by 10,000 IU hCG. MAIN OUTCOME MEASURE(S) First ongoing pregnancy obtained with recFSH-CTP. RESULT(S) Twelve oocytes were retrieved. Ten oocytes were fertilized in vitro by intracytoplasmic sperm injection, and from these 10 oocytes, two embryos were subsequently transferred after 3 days of culture. A pregnancy test 2 weeks after ET was positive, and ultrasound investigation revealed an intact, intrauterine, singleton pregnancy after 12 weeks. CONCLUSION(S) The first pregnancy and live birth was achieved after ovarian stimulation using recFSH-CTP for IVF.

Immature oocyte in-vitro maturation: clinical aspects

The development of immature oocyte collection techniques for in-vitro maturation (IVM), combined with novel culture techniques, opens new possibilities for assisted reproductive technology. Optimization of clinical management of IVM cycles will enhance pregnancy outcome, so that IVM might become an effective alternative assisted reproduction treatment for infertile patients irrespective of the cause of infertility. Parameters such as age and baseline antral follicular count are predictive of outcome and should be used as selection criteria for IVM treatment. Women with polycystic ovary disease and normo-ovulatory patients at risk of developing ovarian hyperstimulation syndrome might benefit from earlier retrieval of oocytes followed by IVM and embryo transfer. HCG priming before oocyte retrieval seems beneficial in terms of oocyte yield and maturational competence, and may increase the harvest of mature oocytes and lead to better endometrial synchronization with the developing embryo. The timing of aspiration may be crucial in IVM and selection criteria for follicle size at aspiration need defining prospectively for infertility type. Finer calibre aspiration needles and low aspiration pressure yield more oocytes. A combination of natural cycle IVF with IVM is a promising, mild and inexpensive assisted reproduction treatment, widely accessible the infertile population.

Avoidance of multiple pregnancies after ovulation induction by supernumerary preovulatory follicular reduction

OBJECTIVE To evaluate the effect of supernumerary preovulatory follicular reduction as an approach to avoid multiple pregnancies in ovulation induction or superovulation cycles. DESIGN Retrospective study. SETTING Tertiary referral center. PATIENT(S) In 26 cycles, 24 patients underwent ovulation induction or superovulation with either clomiphene citrate or hMG. INTERVENTION(S) Selective follicle aspiration was performed before hCG administration. MAIN OUTCOME MEASURE(S) Clinical pregnancy rate and numbers of multiple pregnancies. RESULT(S) A mean number of 4.5 follicles with a diameter > or =15 mm and a mean number of 4.5 follicles with a diameter < or =14 mm were observed before hCG administration. A mean number of 2.3 follicles with a diameter > or =15 mm and a mean number of 1.8 follicles with a diameter < or =14 mm were aspirated before the hCG administration. Seven singleton pregnancies (26.9% per cycle) ensued from the treatment. CONCLUSION(S) Aspiration of supernumerary follicles after ovulation induction or superovulation seems to be a valid approach to avoid multiple pregnancies without affecting pregnancy rate.

Can anti-Müllerian hormone concentrations be used to determine gonadotrophin dose and treatment protocol for ovarian stimulation?

The ability to predict the response potential of women to ovarian stimulation may allow the development of individualized ovarian stimulation protocols. This tailored approach to ovarian stimulation could reduce the incidence of ovarian hyperstimulation syndrome in women predicted to have an excessive response to stimulation or could improve pregnancy outcomes in women classed as poor responders. Namely, variation of the type of gonadotrophin-releasing hormone (GnRH) analogue or the form and dosage of gonadotrophin used for stimulation could be adjusted according to an individuals response potential. The serum concentration of anti-Müllerian hormone (AMH) is established as a reliable marker of ovarian reserve, with decreasing concentrations correlated with reduced response potential. This review examines the current evidence evaluating individualized ovarian stimulation protocols using AMH concentration as a predictive marker of ovarian response. The rationale behind why specific treatment protocols based on individual response potential may be more suitable is also discussed. Based on current evidence, it appears that the use of AMH serum concentrations to predict ovarian response and optimize treatment strategies is a promising approach for improving pregnancy outcomes in women undergoing ovarian stimulation. However, prospective randomized controlled trials evaluating this approach are needed before any firm conclusions can be drawn.

Highly purified HMG versus recombinant FSH for ovarian stimulation in IVF cycles

The objective of this study was to compare the live birth rates resulting from ovarian stimulation with highly purified human menopausal gonadotrophin (HP-HMG), which combines FSH and human chorionic gonadotrophin-driven LH activities, or recombinant FSH (rFSH) alone in women undergoing IVF cycles. An integrated analysis was performed of the raw data from two randomized controlled trials that were highly comparable in terms of eligibility criteria and post-randomization treatment regimens with either HP-HMG or rFSH for ovarian stimulation in IVF, following a long down-regulation protocol. All randomized subjects who received at least one dose of gonadotrophin in an IVF cycle (HP-HMG, n = 491; rFSH, n = 495) were included in the analysis. Subjects who underwent intracytoplasmic sperm injection cycles were excluded. The superiority of one gonadotrophin preparation over the other was tested using the likelihood ratio test in a logistic regression analysis. The live birth rate per cycle initiated was 26.5% (130/491) with HP-HMG and 20.8% (103/495) with rFSH (P = 0.041). The odds ratio in favour of HP-HMG was 1.36 (95% confidence interval: 1.01-1.83). Thus, the findings of this integrated analysis demonstrate that ovarian stimulation with HP-HMG, following a long down-regulation protocol, in IVF cycles results in significantly more live births than stimulation with rFSH alone.