Ester Vidal

Ovarian responses to recombinant FSH or HMG in normogonadotrophic women following pituitary desensitization by a depot GnRH agonist for assisted reproduction

At present, there is considerable debate about the utility of supplemental LH in assisted reproduction treatment. In order to explore this, the present authors used a depot gonadotrophin-releasing hormone agonist (GnRHa) protocol combined with recombinant human FSH (rhFSH) or human menopausal gonadotrophin (HMG) in patients undergoing intracytoplasmic sperm injection (ICSI). The response to either rhFSH (75 IU FSH/ampoule; group rhFSH, 25 patients) or HMG (75 IU FSH and 75 IU LH/ampoule; group HMG, 25 patients) was compared in normo-ovulatory women suppressed with a depot triptorelin injection and candidates for ICSI. A fixed regimen of 150 IU rhFSH or HMG was administered in the first 14 days of treatment. Treatment was monitored with transvaginal pelvic ultrasonographic scans and serum measurement of FSH, LH, oestradiol, androstenedione, testosterone, progesterone, inhibin A, inhibin B and human chorionic gonadotrophin (HCG) at 2-day intervals. Although oestradiol serum concentrations on the day of HCG injection were similar, both the duration of treatment and the per cycle gonadotrophin dose were lower in group HMG. In the initial 16 days of gonadotrophin treatment, the area under the curve (AUC) of LH, oestradiol, androstenedione and inhibin B were higher in group HMG; no differences were seen for the remaining hormones measured, including the inhibin B:inhibin A ratio. The dynamics of ovarian follicle development during gonadotrophin treatment were similar in both study groups, but there were more leading follicles (>17 mm in diameter) on the day of HCG injection in the rhFSH group. The number of oocytes, mature oocytes and good quality zygotes and embryos obtained were significantly increased in the rhFSH group. It is concluded that in IVF patients undergoing pituitary desensitization with a depot agonist preparation, supplemental LH may be required in terms of treatment duration and gonadotrophin consumption. However, both oocyte, embryo yield and quality were significantly higher with the use of rhFSH.

Outcome from consecutive assisted reproduction cycles in patients treated with recombinant follitropin alfa filled-by-bioassay and those treated with recombinant follitropin alfa filled-by-mass

Recent advances in manufacturing procedures for r-hFSH have resulted in a preparation (follitropin alfa) that is highly consistent in both isoform profile and glycan species distribution. As a result, follitropin alfa can be reliably quantified and vials can be filled by mass. This study compared the clinical results in a well-established assisted reproduction programme during the crossover from standard follitropin alfa filled-by-bioassay (FSH-bio) to follitropin alfa filled-by-mass (FSH-mass). The study included the last 125 patients treated with FSH-bio and the first 125 patients receiving FSH-mass for ovarian stimulation in their first assisted reproduction treatment cycle. Patient baseline characteristics were almost identical in the two groups. The duration of ovarian stimulation was significantly shorter in the FSH-mass group. The number of patients receiving the HCG injection and undergoing oocyte retrieval, follicular development and the serum concentration of oestradiol on the day of HCG injection were similar for the two treatment groups. The oocyte yield and the fertilization rates were similar in both groups of patients. However, embryo quality and implantation rates were significantly higher in the FSH-mass group. Accordingly, in spite of the mean number of embryos transferred being significantly lower in the FSH-mass group, there was a trend for higher clinical pregnancy rates in this group of patients. It is concluded that the new formulation of FSH-mass is more effective than the standard FSH-bio in terms of embryo quality, implantation rates, and number of days of stimulation.

Early Hormonal Markers of Pregnancy Outcome After In Vitro Fertilization and Embryo Transfer

AbstractPurpose: To investigate the relative power of HCG, estradiol, and progesterone determinations in the prediction of pregnancy outcome after IVF. These prognostic hormonal factors were studied as single and combined predictors. Methods: Serum concentrations of β-HCG, progesterone, and estradiol were measured 12–13 days after embryo transfer (study point 1) and 7 days later (study point 2) in a series of 20 consecutive infertile patients having a first-trimester spontaneous clinical abortion after an IVF-embryo transfer cycle. As a control group (n=60), the next three IVF-embryo transfer cycles resulting in an ongoing pregnancy after each miscarried IVF cycle in our assisted reproduction program was used. The discrimination attained between the two study groups (ongoing pregnancies and miscarriages) was evaluated by logistic regression and receiver operating characteristic (ROC) curve analysis. Results: Mean hormone concentrations at study points 1 and 2 were higher in the ongoing pregnancy than in the abortion group. Regarding pregnancy outcome the percentage increment of HCG serum levels (≥1321%), with an accuracy (predictive value of pregnancy outcome) of 81.2% (sensitivity 98%, specificity 50%), had the best prognostic reliability but no significant differences were found when this parameter was compared with the predictive value of HCG concentration (≥72 IU/l) at study point 1 (diagnostic accuracy 80.5%; sensitivity 70%; specificity 80%). When ROC analysis was used, the best predictor of ongoing pregnancy according to the AUCROC was HCG concentration at study point 2 but again no significant differences were found when this parameter was compared with the predictive value of HCG serum levels at study point 1. A multiple marker strategy did not help distinguish viable from nonviable pregnancies. Conclusion: A single, early (days 12–13 after embryo transfer) HCG quantitative serum measurement in IVF cycles not only is diagnostic but also has good predictive value for pregnancy outcome.

Delayed Motherhood Increases the Probability of Sons to be Infertile

AbstractPurpose: To ascertain whether advanced maternal age at birth is associated with offspring infertility. Methods: A written questionnaire was completed by infertile couples attending our clinic in the presence of a researcher. Results: Maternal age at birth (odds ratio 1.236, 95% CI 1.100–1.388) and birth order of all respondents and their respective siblings (odds ratio 0.551, 95% CI 0.351–0.865) were significant predictors of male infertility. The probability of a man being infertile increased as mothers age at birth increased (regression coefficient ± standard error 0.212 ± 0.059; P < 0.001), but decreased as birth order increased (regression coefficient ± standard error −0.596 ± 0.230; P = 0.010). Conclusions: Delayed motherhood may enhance the probability of sons to be infertile. The probability of a man being infertile would be greater if he comes from a small family than if he comes from a large family.

Increased live birth rate in twin pregnancies resulting from embryo assistance.

OBJECTIVE: To estimate why the live birth rate per implanted embryo is higher in twin than in singleton pregnancies. METHODS: Data from 1,159 singleton and 523 dichorionic twin pregnancies, obtained after assisted conception, were included. To account for the higher live birth rate observed in twin pregnancies, two possibilities were considered: embryo collaboration and assistance. To test these hypotheses, we compared the observed values for each possible outcome in twin pregnancies (double birth, single birth, double loss) with the expected values regarding as the null hypothesis that the survival of either embryo is independent from the presence of the other. The effect of maternal age was also examined. RESULTS: Live birth rate, per implanted embryo, was higher in twin than in singleton pregnancies: 83% compared with 76% (odds ratio 1.53, 95% confidence interval 1.24–1.88; P<.001). There were significant differences between the observed outcomes in twin pregnancies and those expected assuming no interaction between embryos (P<.001). The number of double births was higher than expected (71.9% observed compared with 57.7% expected), whereas single births were lower to a similar extent (22% observed compared with 36.5% expected). In contrast, observed and expected double losses were similar (6.1% observed compared with 5.8% expected). Although the overall rate of miscarriage was higher for women aged 34 years and older, the difference in live birth rate between twin and singleton pregnancies was 2.4-fold higher than in younger women. CONCLUSION: The higher live birth rate occurring in twin pregnancies can be accounted for by assistance, whereby some embryos that would fail as singletons survive in a twin pregnancy when implanted along with a fit sibling. This effect is more pronounced in older mothers. LEVEL OF EVIDENCE: III

Transmyometrial embryo transfer as a useful method to overcome difficult embryo transfers - a single-center retrospective study

Objective Pregnancy after an embryo transfer depends largely on embryo quality, endometrial receptivity, and the technique used in the embryo transfer. Embryo transfers have been reported as inevitably traumatic and difficult for 5-7% of patients in assisted reproduction treatment. In these cases, transmyometrial embryo transfer should be considered as a suitable method to overcome difficult embryo transfers. The aim of this study was to report our experience with this technique and analyze its causes, results and complications. Methods Since 1993, 39 women (40 cycles of assisted reproductive technology treatment) were submitted to transmyometrial embryo transfers in our center. The procedures were carried out as described by the Towako group. Results The enrolled female patients had a mean age of 34 years and a mean baseline FSH level of 6.89 IU/mL. The median number of retrieved oocytes was 7.50 and a mean of 2.63 embryos were transferred. Implantation rate was 9.5%. With respect to clinical results, pregnancy and miscarriage rates were 25% and 30%, respectively. Since there were two twin pregnancies, the live birth rate was 22.5% (9/40). No major complications were reported. Conclusion Transmyometrial embryo transfer can and should be an option in cases of difficult/impossible transcervical embryo transfer.