Paul Devroey

Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte

Intracytoplasmic sperm injection (ICSI) is a promising assisted-fertilisation technique that may benefit women who have not become pregnant by in-vitro fertilisation (IVF) or subzonal insemination (SUZI) of oocytes. We have used ICSI to treat couples with infertility because of severely impaired sperm characteristics, and in whom IVF and SUZI had failed. Direct injection of a single spermatozoon into the ooplasm was done in 47 metaphase-II oocytes: 38 oocytes remained intact after injection, 31 became fertilised, and 15 embryos were replaced in utero. Four pregnancies occurred after eight treatment cycles--two singleton and one twin pregnancy, and a preclinical abortion. Two healthy boys have been delivered from the singleton pregnancies and a healthy boy and girl from the twin pregnancy.

Pregnancies after testicular sperm extraction and intracytoplasmic sperm injection in non-obstructive azoospermia

In this study (May 1 until August 31, 1994) a total of 15 azoospermic patients suffering from testicular failure were treated with a combination of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI). Spermatozoa were available for ICSI in 13 of the patients. Out of 182 metaphase II injected oocytes, two-pronuclear fertilization was observed in 87 (47.80%); 57 embryos (65.51%) were obtained for either transfer or cryopreservation. Three ongoing pregnancies out of 12 replacements (25%) were established, including one singleton, one twin and one triplet gestation. The ongoing implantation rate was 18% (six fetal hearts out of 32 embryos replaced).

Consensus on infertility treatment related to polycystic ovary syndrome

The treatment of infertile women with polycystic ovary syndrome (PCOS) is surrounded by many controversies. This paper describes, on the basis of the currently available evidence, the consensus reached by a group of experts regarding the therapeutic challenges raised in these women. Before any intervention is initiated, preconceptional counselling should be provided emphasizing the importance of life style, especially weight reduction and exercise in overweight women, smoking and alcohol consumption. The recommended first-line treatment for ovulation induction remains the anti-estrogen clomiphene citrate (CC). Recommended second-line intervention, should CC fail to result in pregnancy, is either exogenous gonadotrophins or laparoscopic ovarian surgery (LOS). The use of exogenous gonadotrophins is associated with increased chances for multiple pregnancy and, therefore, intense monitoring of ovarian response is required. LOS alone is usually effective in <50% of women and additional ovulation induction medication is required under those circumstances. Overall, ovulation induction (representing the CC, gonadotrophin paradigm) is reported to be highly effective with a cumulative singleton live birth rate of 72%. Recommended third-line treatment is in vitro fertilization. More patient-tailored approaches should be developed for ovulation induction based on initial screening characteristics of women with PCOS. Such approaches may result in deviation from the above mentioned first-, second- or third-line ovulation strategies in well-defined subsets of patients. Metformin use in PCOS should be restricted to women with glucose intolerance. Based on recent data available in the literature, the routine use of this drug in ovulation induction is not recommended. Insufficient evidence is currently available to recommend the clinical use of aromatase inhibitors for routine ovulation induction. Even singleton pregnancies in PCOS are associated with increased health risk for both the mother and the fetus.

Sperm characteristics and outcome of human assisted fertilization by subzonal insemination and intracytoplasmic sperm injection

Objective To investigate the influence of sperm characteristics on the treatment by subzonal insemination (SUZI) and intracytoplasmic sperm injection of couples with severe male infertility. Design A retrospective analysis of 300 consecutive cycles of assisted fertilization concerning 202 infertile couples was performed. One hundred fifty-three couples underwent 362 unsuccessful IVF cycles, whereas on 49 couples IVF was not performed because of poor sperm characteristics. Setting Procedures were performed in an institutional research environment. Patients, Participants Couples in which the male partner was the presumed cause of repeated failure to achieve conception by IVF or in which seminal parameters were unacceptable for IVF. Interventions Three hundred transvaginal oocyte retrievals were performed after superovulation by GnRH agonist and gonadotropins. Main Outcome Measures After SUZI and intracytoplasmic sperm injection the following parameters were evaluated: fertilization, cleavage, pregnancy, and implantation rates in relation to the sperm parameters and the proportion of acrosome-free spermatozoa after different treatments. Results Normal fertilization occurred in 18% of the oocytes treated by SUZI and in 44% after intracytoplasmic sperm injection. Only the treatment by electroporation showed a positive correlation with the fertilization rate. Fourteen pregnancies were obtained after SUZI, 8 pregnancies after intracytoplasmic sperm injection, and 8 pregnancies after a combination of the two procedures. A score calculated from the sperm parameters after selection correlated with the fertilization obtained after SUZI, whereas a score calculated from the parameters before sperm selection correlated with the pregnancy rate. Sperm morphology influenced the implantation rate of the embryos obtained with these two procedures. Conclusions Intracytoplasmic sperm injection and SUZI can successfully treat couples who fail IVF or who cannot benefit from IVF. Different treatments can be applied to semen samples to increase the number of acrosome-reacted spermatozoa. The few significant relations found between sperm characteristics and the outcome of assisted fertilization cannot predict the outcome.

Multiple birth resulting from ovarian stimulation for subfertility treatment

Assisted reproductive technologies (ARTs) aim to increase a womans chances of becoming pregnant by bringing many female and male gametes into close proximity. Techniques to achieve this objective include ovarian hyperstimulation by maturation of several oocytes, intrauterine insemination (IUI) of concentrated sperm, or in-vitro fertilisation (IVF) by bringing gametes together outside the female body. The very nature of ovarian hyperstimulation--with or without IUI--enhances the risk of multiple pregnancy (eg, two or more babies). In most IVF cycles, more than one embryo is transferred, again resulting in an increased chance of multiple pregnancy. Developed societies have witnessed a large rise in prevalence of twin, triplet, and higher order multiple births, mainly resulting from ARTs. The primary aim of this Review is to increase awareness of the many implications of the present iatrogenic epidemic of multiple births. The background of ovarian hyperstimulation, trends supporting current practice, and strategies to reduce the chance of multiple pregnancy are highlighted.

Microsurgical epididymal sperm aspiration and intracytoplasmic sperm injection : a new effective approach to infertility as a result of congenital bilateral absence of the vas deferens

OBJECTIVE To present and assess the efficacy of a new approach for the treatment of infertility due to congenital bilateral absence of the vas deferens. DESIGN A retrospective study of consecutive trials. SETTING Centre for Reproductive Medicine, which is a tertiary referral institution. PATIENTS Twelve couples suffering from infertility because of congenital bilateral absence of the vas deferens. INTERVENTIONS A microsurgical epididymal sperm aspiration procedure was performed in the husbands, followed by intracytoplasmic sperm injection of oocytes recovered from the wives. Cleaving embryos were transferred to the uterine cavity 48 hours after the intracytoplasmic sperm injection procedure. MAIN OUTCOME MEASURES Sperm parameters after microsurgical epididymal sperm aspiration, fertilization, cleavage, and pregnancy rates. RESULTS In all 14 microsurgical epididymal sperm aspiration procedures, sperm was retrieved. Notwithstanding the poor quality of this epididymal sperm, a fertilization rate of 58% was achieved after intracytoplasmic sperm injection. On 10 occasions, embryos were transferred and five patients became pregnant, i.e., an overall pregnancy rate of 35.7% per started trial and 50.0% per transfer. Another two patients became pregnant after replacement of frozen-thawed embryos, which increases the pregnancy rate to 50.0% per microsurgical epididymal sperm aspiration procedure. Early pregnancy wastage was 57%, limiting the ongoing pregnancy rate to 21.4% per microsurgical epididymal sperm aspiration procedure. CONCLUSION This study shows the combined microsurgical epididymal sperm aspiration-intracytoplasmic sperm injection procedure to be highly efficient in achieving fertilization in vitro, even after recovery of grossly impaired epididymal sperm.

Primary ovarian insufficiency

Primary ovarian insufficiency is a subclass of ovarian dysfunction in which the cause is within the ovary. In most cases, an unknown mechanism leads to premature exhaustion of the resting pool of primordial follicles. Primary ovarian insufficiency might also result from genetic defects, chemotherapy, radiotherapy, or surgery. The main symptom is absence of regular menstrual cycles, and the diagnosis is confirmed by detection of raised follicle-stimulating hormone and declined oestradiol concentrations in the serum, suggesting a primary ovarian defect. The disorder usually leads to sterility, and has a large effect on reproductive health when it arises at a young age. Fertility-preservation options can be offered to some patients with cancer and those at risk of early menopause, such as those with familial cases of primary ovarian insufficiency. Long-term deprivation of oestrogen has serious implications for female health in general; and for bone density, cardiovascular and neurological systems, wellbeing, and sexual health in particular.

Using ejaculated, fresh, and frozen-thawed epididymal and testicular spermatozoa gives rise to comparable results after intracytoplasmic sperm injection*

OBJECTIVE To describe the preparation of fresh or frozen-thawed epididymal and testicular sperm for intracytoplasmic single sperm injection and to compare the fertilization, embryo quality, and pregnancy rates (PRs) obtained after using these spermatozoa to the results when freshly ejaculated sperm was used for microinjection. DESIGN Retrospective analysis of 1,034 consecutive microinjection cycles. Ejaculated (965 cycles), fresh epididymal (43 cycles), frozen-thawed epididymal (9 cycles), and testicular sperm (17 cycles) was used for intracytoplasmic sperm injection. SETTING Procedures were performed in a tertiary IVF center coupled with an institutional research environment. MAIN OUTCOME MEASURES Semen density and motility were judged by the World Health Organization criteria and sperm morphology was evaluated by the Tygerbergs strict criteria. After microinjection, oocyte intactness, fertilization, embryo cleavage, transfer, and PRs were evaluated and compared. RESULTS The median values of total sperm count, total motility and normal morphology were 17.85 x 10(6), 37%, 8% for freshly ejaculated sperm; 46.20 x 10(6), 12%, 9% for fresh epididymal sperm; 0.15 x 10(6), 0%, 0% for frozen-thawed epididymal sperm; and 0.54 x 10(6), 0% for testicular sperm (morphology was not determined). The percentage of intact oocytes after microinjection ranged from 84% to 90%. Normal fertilization rates were high when fresh or frozen-thawed epididymal and testicular spermatozoa were used for the injection (56%, 56%, 48%, respectively) but were significantly lower than for ejaculated sperm (70%). There was a higher proportion of transferable embryos obtained after ejaculated sperm injection than after testicular sperm injection. Forty percent, 58%, 33%, and 46% of cycles had positive serum hCG using ejaculated, fresh, or frozen-thawed epididymal and testicular sperm. Initial pregnancy loss occurred in 26.3% of the conception cycles. CONCLUSION Intracytoplasmic sperm injection can provide high normal fertilization, cleavage, and PRs when fresh or frozen-thawed epididymal and testicular spermatozoa are used, but normal fertilization rates are significantly lower than after microinjection with ejaculated sperm.

Effect of ovarian stimulation with recombinant follicle-stimulating hormone, gonadotropin releasing hormone antagonists, and human chorionic gonadotropin on endometrial maturation on the day of oocyte pick-up

OBJECTIVE To assess the effect of ovarian stimulation with recombinant FSH, GnRH antagonists, and hCG on endometrial maturation on the day of oocyte pick-up. DESIGN Prospective study. SETTING Tertiary referral center. PATIENT(S) Fifty-five women undergoing controlled ovarian hyperstimulation for IVF/intracytoplasmic sperm injection (ICSI). INTERVENTION(S) [1] Ovarian stimulation with recombinant FSH, starting on day 2 of the cycle and GnRH antagonist, starting after a median of 6 days of recombinant FSH stimulation (range, 5-12 days); [2] hCG administration for ovulation induction; and [3] aspirational biopsy of endometrium at oocyte pick-up. MAIN OUTCOME MEASURE(S) Endometrial histology at oocyte pick-up by Noyes criteria. RESULT(S) Advancement of endometrial maturation (2.5 +/- 0.1 days) as compared to the expected chronological date was observed in all antagonist cycles at oocyte retrieval. Endometrial advancement at oocyte pick-up increased in line with values of LH at initiation of stimulation and the duration of recombinant FSH treatment before the antagonist was started. CONCLUSION(S) The higher the values of LH at initiation of stimulation and the longer the duration of recombinant FSH treatment before the antagonist is started, the more advanced the endometrial maturation at oocyte pick-up.

Comparison of different doses of gonadotropin-releasing hormone antagonist Cetrorelix during controlled ovarian hyperstimulation

OBJECTIVE To assess the minimal effective dose of a GnRH antagonist (Cetrorelix; Asta Medical; Frankfurt, Germany) to prevent premature LH surge in patients undergoing controlled ovarian hyperstimulation (COH) for assisted reproductive technologies. DESIGN In 69 patients COH was carried out with the association of hMG, starting on day 2 of the menstrual cycle, and a GnRH antagonist (Cetrorelix) was administered from day 6 of the hMG treatment (day 7 of the menstrual cycle) every day up to and including the last day of the hMG injection. In 32 and 30 patients, 0.5 mg and 0.25 mg of Cetrorelix were administered, respectively. Seven patients received 0.1 mg of Cetrorelix. SETTING Tertiary referral center. RESULT(S) No premature endogenous LH surge occurred in patients treated with 0.5 and 0.25 mg of Cetrorelix, and serum LH concentrations were maintained constantly low during the entire follicular phase in both groups. Follicle-stimulating hormone, LH, E2, and P expressed as area under the curve were similar in both groups. A premature LH surge (18 mIU/mL; conversion factor to SI unit, 1.00) with a concomitant P rise (1.7 micrograms/L; conversion factor to SI unit, 3.180) occurred in one of the seven patients treated with 0.1 mg Cetrorelix; therefore, treatment with this dose was discontinued. CONCLUSION(S) The minimal effective dose of Cetrorelix able to prevent premature LH surge in COH cycles is 0.25 mg administered daily.