M. Camus

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).

Neonatal outcome of 937 children born after transfer of cryopreserved embryos obtained by ICSI and IVF and comparison with outcome data of fresh ICSI and IVF cycles

BACKGROUND To evaluate the safety of cryopreservation in combination with IVF and ICSI, prenatal diagnosis and neonatal outcome were investigated in children conceived from frozen-thawed ICSI embryos (cryo ICSI) and frozen-thawed IVF embryos (cryo IVF). Data were also compared with earlier published results from fresh ICSI and IVF embryos. METHODS Questionnaire data and results of physical examination at 2 months of 547 cryo ICSI children and 390 cryo IVF children were compared, and these were also compared with those of infants born after transfer of fresh embryos. RESULTS Birth characteristics were comparable for cryo ICSI and cryo IVF infants. Cryo singletons showed a trend towards higher mean birthweight compared with fresh singletons, in ICSI and IVF, reaching significance when all cryo (ICSI plus IVF) singletons were considered. Low birthweight rate according to multiplicity was comparable between the fresh and the cryo groups, in ICSI and IVF. Non-statistically significantly increased rates of de novo chromosomal anomalies (3.2%) were found in cryo ICSI fetuses/children compared with the fresh ICSI group (1.7%) (OR 1.96; 95% CI 0.92-4.14). Major malformations were more frequently observed in cryo ICSI live borns (6.4%) than in cryo IVF live borns (3.1%) (OR 2.15; 95% CI 1.10-4.20) and fresh ICSI live borns (3.4%) (OR 1.96; 95% CI 1.31-2.91). CONCLUSIONS In cryo ICSI compared with cryo IVF, prenatal and neonatal outcome results were comparable, except for a higher major malformation rate in the cryo ICSI group. In the total cryo group compared with the total fresh group, we found a higher mean birthweight in singletons and a higher major malformation rate in live borns.

Clomiphene citrate versus letrozole for ovarian stimulation: A pilot study

The purpose of this pilot study was to compare the endocrinological environment of cycles stimulated with clomiphene citrate (CC) or letrozole. Fifteen patients undergoing intrauterine insemination (IUI) received from day 3 to day 7 of the cycle either letrozole 2.5 mg/day (n = 7) or clomiphene citrate 100 mg/day (n = 8). IUI was performed one day after the detection of LH peak. No luteal support was administered. Significantly lower serum oestradiol concentrations were present in the follicular phase on days 9, 13 and 15 of the cycle and in the luteal phase on days 3 and 6 post-IUI in the letrozole group compared with those in the CC group. Progesterone concentrations and oestradiol concentrations were significantly lower in the letrozole group than in the CC group on the day of LH peak. Significantly more follicles developed in patients in the CC group compared with those in the letrozole group. In conclusion, significantly lower oestradiol concentrations and fewer follicles are observed in cycles stimulated with 2.5 mg letrozole compared with cycles stimulated with 100 mg CC from day 3 to day 7 of the cycle.

Early pregnancy loss is significantly higher after day 3 single embryo transfer than after day 5 single blastocyst transfer in GnRH antagonist stimulated IVF cycles

The current study aimed to investigate whether single day-3 embryo transfer (SET) results in higher early pregnancy loss (EPL) than single blastocyst transfer (SBET). A total of 896 patients underwent 1103 IVF cycles with a gonadotrophin-releasing hormone (GnRH) antagonist protocol. In 603 cycles (D3 group) a single embryo on day 3 of the embryo culture was transferred, whereas in the remaining 500 cycles a single blastocyst was transferred on day 5 (D5 group). Multifollicular ovarian stimulation was performed with a GnRH antagonist protocol starting on day 6. SET resulted in 209 pregnancies (34.7%), compared with 221 pregnancies (44.2%) for SBET. Early pregnancy loss rate was significantly higher with SET compared with SBET (26.8% versus 17.2%, P = 0.017) and ongoing implantation rate was also significantly higher with day 5 compared with day-3 embryo transfer (OR:1.68, 95% confidence interval:1.31-2.18). Sub-optimal embryo selection for transfer on day 3, in addition to asynchronization between altered endometrium and early exposure of cleavage-stage embryos, might explain the above difference. Nevertheless, the higher implantation potential of the blastocyst questions the rationale behind performing single embryo transfer on day 3 of embryo culture in women under 36 years old.

Cryopreserved embryo transfer in an artificial cycle: is GnRH agonist down-regulation necessary?

The use of GnRH agonist downregulation in artificial endometrium priming cycles for cryopreserved embryo transfer was retrospectively investigated to establish whether higher live birth rates resulted. Six hundred and ninety-nine patients underwent 1129 artificial endometrium priming cycles for the transfer of cryopreserved embryos between 1 July 2009 and 1 June 2012. Hormonal supplementation with (group A, n = 280 cycles) or without (group B, n = 849 cycles) GnRH agonist co-treatment was given. Live birth rates were comparable between the two groups per started cycle (14.9% [41/275] in group A versus 15.1% [127/839] in group B) or per embryo transfer (17.5% [41/234] in group A versus 17.6% [127/723] in group B). After logistic regression analysis, the only variables that were significantly associated with live birth rates were day of embryo transfer (OR 0.69; 95% CI 0.48 to 0.98) for day 3 versus day 5 embryos, the number of embryos transferred (OR 2.13; 95% CI 1.58 to 2.86) for two embryos versus one embryo transferred and the endometrial thickness on the day of embryo transfer (OR 1.15; 95% CI 1.05 to 1.25). Live birth rates after cryopreserved embryo transfer in artificial cycles did not increase when a GnRH agonist was administered.

Should requests for donor insemination on social grounds be expanded to transsexuals

Donor insemination may provide an answer to transsexuals with female partners who have a wish for a child. Although the follow-up on children born in the context of these families is non-existent and the follow-up on transsexuals after sex reassignment surgery (SRS) is limited, fertility centres might consider accepting the requests of transsexuals with a female partner. Between 1997 and 2001, nine couples presented themselves at the Centre for Reproductive Medicine of the Dutch-speaking Brussels Free University, of whom five couples were accepted. Nevertheless, some caution is called for because transsexualism is socially not accepted. Moreover, transsexualism is still considered to be psychiatric condition. The following recommendations should be taken in consideration. Treatment should be limited to female-to-male transsexuals with a female partner. A multidisciplinary team of specialists should carry out the diagnosis for gender identity. Developmental problems of the gender-disordered child might interfere with socio-economic, psychological and emotional stability in adulthood. The period of sex reassignment should be nearly completed.

Should an intrauterine insemination with donor semen be performed 1 or 2 days after the spontaneous LH rise? A prospective RCT

STUDY QUESTION What is the impact on pregnancy rates when intrauterine insemination (IUI) is performed 1 or 2 days after the spontaneous LH rise? SUMMARY ANSWER IUI 1 day after the spontaneous LH rise results in significantly higher clinical pregnancy rates compared with IUI performed 2 days after the LH rise. WHAT IS KNOWN ALREADY IUI is scheduled within a limited time interval during which successful conception can be expected. Data about the optimal timing of IUI are based on inseminations following ovarian stimulation. There is no available evidence regarding the correct timing of IUI in a natural menstrual cycle following the occurrence of a spontaneous LH rise. STUDY DESIGN, SIZE, DURATION A prospective RCT, including patients undergoing IUI with donor sperm in a natural menstrual cycle. IUI cycles (n = 435) were randomized between October 2010 and April 2013, of which 23 were excluded owing to protocol deviation and 412 received the allocated intervention. PARTICIPANTS/MATERIALS, SETTING, METHODS Serial serum LH concentrations were analysed in samples taken between 07:00 and 09:00 h to detect an LH rise from Day 11 of the cycle onwards. The subjects were randomized to receive insemination either 1 or 2 days after the observed LH rise. In the final analysis, there were 213 cycles in the group receiving IUI 1 day after the LH rise and 199 cycles in the group receiving IUI 2 days after the LH rise. MAIN RESULTS AND THE ROLE OF CHANCE Significantly higher clinical pregnancy rates per IUI cycle were observed in patients undergoing IUI 1 day after the LH rise when compared with patients undergoing IUI 2 days after the LH rise [19.7 (42/213) versus 11.1% (22/199), P = 0.02]. In view of the timing of sampling for LH, the inseminations were performed at 27 h (±2 h) and 51 h (±2 h) after detection of the LH rise. The risk ratio of achieving a clinical pregnancy if IUI was scheduled 1 day after the LH rise compared with 2 days was 1.78 [95% confidence interval (CI), 1.11-2.88]. This points towards a gain of one additional clinical pregnancy for every 12 cycles performed 1 day instead of 2 days after the LH rise. When analysing the results per patient, including only women who underwent their first treatment cycle of insemination, the outcome was in line with the per cycle analysis, demonstrating an 8% difference in pregnancy rate in favour of the early group (20.5 versus 12.2%), however, this difference was not significant. LIMITATIONS, REASONS FOR CAUTION Optimal monitoring for the occurrence of the LH rise involves several daily LH measurements, which is not always amenable to everyday clinical practice, however, daily sampling was sufficient to detect a significant difference in pregnancy rate. The strict inclusion of a highly selected population of patients who underwent IUI in a natural cycle may have been a limitation. IUI in a natural menstrual cycle confers lower success rates compared with IUI following ovarian stimulation and is not suitable for patients with ovulatory dysfunction. Furthermore, a similar study in a larger number of women is required to confirm the result in terms of pregnancy rate per patient. WIDER IMPLICATIONS OF THE FINDINGS This is the first RCT to show that timing of IUI in a natural menstrual cycle is important and that IUI should be performed 1 day after the LH rise, rather than 2 days post-LH rise. Daily monitoring of the rise in LH, as performed in our study, can be adopted to achieve a higher pregnancy rate per IUI cycle. STUDY FUNDING/COMPETING INTEREST(S) No funding was received for this study. All authors declare to have no conflict of interest with regard to this trial. TRIAL REGISTRATION NUMBER The trial was registered at clinicaltrials.gov (NCT01622023).

Intracytoplasmic sperm injection — ICSI

For more than a decade in vitro fertilization (IVF) has been successful in the treatment of couples with long-standing infertility due to various aetiologies such as tubal disease, male-factor infertility, unexplained infertility and endometriosis. The usual fertilization rate in IVF for nonmale infertility cases is 60–70% of the inseminated cumulus-oocyte complexes and in andrological infertility it is only 20–30%. The lower the number of normally fertilized oocytes, the less chance there is of available embryos, so that patients may have no embryos to transfer. It has been the experience of all centres for reproductive medicine, including our own, that a certain number of couples with male-factor infertility cannot be helped by standard IVF treatment. After insemination with progressively motile spermatozoa the number of two-pronuclear oocytes was either zero or less than 5%. Furthermore, a sizeable number of couples cannot be accepted for IVF if the number of progressively motile spermatozoa in the ejaculate is below a certain threshold number such as 500 000. In the past five years, assisted fertilization procedures have been developed to circumvent the barriers that prevent sperm access to the ooplasma, namely the zona pellucida and the ooplasmic membrane. Pregnancies and births have been reported after partial zona dissection (PZD) and subzonal insemination (SUZI). The success rate of PZD and SUZI has remained moderate: the normal fertilization rate (two-pronuclear oocytes) has never exceeded 20–25% of the micromanipulated oocytes; only two-thirds of the patients have had embryo transfers of, usually, a low number of embryos, resulting in a reduced pregnancy and take-home baby rate.

Inhibition of gonadotropic and ovarian function by intranasal administration of D-Ser (TBU)6-EA10-LHRH in normo-ovulatory women and patients with polycystic ovary disease

We investigated the effectiveness of D-Ser (TBU)6-EA10-LHRH (Buserelin) intranasally 600 μg/day given 6 times daily in desensitizing normal ovulatory women and patients with polycystic ovarian disease (PCOD) before initiation of ovarian stimulation for in vitro fertilization. We found that this regimen was sufficient to suppress the gonadotrophs in the normal women and in 8 out of 10 PCOD patients. In PCOD ovarian hormones became normal after Buserelin administration. Adrenal steroidogenesis was not affected by the GnRH agonist. We suggested that the frequency of administration of Buserelin was important to achieve a constant receptor binding and consequently a rapid desensitization. The choice of a monoclonal immunoradiometric assay for luteinizing hormone (LH) and follicle stimulating hormone (FSH) in association with the estradiol-benzoate provocation test were essential in evaluating desensitization.

Pregnancy outcome and neonatal data on children born after ICSI with testicular sperm in obstructive and non-obstructive azoospermia

BACKGROUND Registries on outcome of ICSI pregnancies obtained with testicular sperm do not differentiate between obstructive (OA) and non-obstructive azoospermia (NOA). We evaluated the pregnancy outcome and neonatal data on children born after ICSI using testicular sperm of men with histologically proven OA or NOA. METHODS Pregnancies obtained after ICSI using testicular sperm of men with defined NOA (n = 70) were compared with those of men with OA (n = 204). RESULTS Multiple birth rates in NOA and OA couples, respectively, were 21 versus 27% (P = NS), overall preterm delivery rates were 38 versus 26% (NS), and prematurity rates were 24 versus 13% for singletons (NS) and 86 versus 54% for twins (relative risk 1.59, 95% confidence interval 1.04-2.42). Median gestational age for singletons was 38.3 versus 39.3 weeks, respectively (P < 0.05). The low birth weight rates were 34 versus 31%, respectively (NS). The early perinatal mortality rate was 66 versus 15 per 1000 births, respectively, (NS). Major congenital malformations were observed in 4 versus 3%, respectively, of the live born babies (NS). Prenatal karyotypes showed 7% de-novo abnormalities in the NOA group versus 1% in the OA group (NS). CONCLUSIONS Our data do not show differences between NOA and OA pregnancies except for a strong tendency towards a lower gestational age in singletons and a higher percentage of premature twins in the NOA group. Although our data are based on a limited sample, the differences observed call for further analysis. Given the low pregnancy rates after ICSI with NOA, a multicentre study, differentiating NOA and OA patients, would be recommended.