Candido Tomás

Elective single embryo transfer with cryopreservation improves the outcome and diminishes the costs of IVF/ICSI

BACKGROUND Although elective single embryo transfer (eSET) minimizes the multiple birth rate after in vitro fertilization (IVF)/intra cytoplasmic sperm injection (ICSI), there remain concerns in many countries that it is less effective and more expensive than conventional double embryo transfer (DET). METHODS We compared the clinical outcome achieved in the years 1995-1999, in which eSET was rarely used (4.2% of women, DET period) with that of the years 2000-2004, in which eSET was more widely used (46.2%, eSET period). In the DET period, 826 women had 1359 fresh embryo cycles followed by 589 frozen-thawed embryo transfer (FET) cycles. In the eSET period, 684 women had 1027 fresh and 683 FET cycles. The cumulative term live birth rate/woman was the primary clinical outcome measure. An incremental cost-effectiveness ratio of a term live birth was also calculated based on hospital charges and medication prices of IVF/ICSI treatment. RESULTS The cumulative pregnancy rate/oocytes pickup (38.2 versus 33.1%, P = 0.01), cumulative live birth rate/oocytes pickup (28.0 versus 22.5%, P = 0.002) and cumulative live birth rate/woman (41.7 versus 36.6%, P = 0.04) were all higher in the eSET period than in the DET period. The cumulative multiple birth rate was significantly lower in the eSET period than in the DET period (8.9 versus 19.6%, P < 0.0001). A term live birth in the eSET period was 19 889 euros less expensive than in the DET period. CONCLUSIONS This study shows that eSET with cryopreservation is more effective and less expensive than DET and should be adopted as a treatment of choice.

Improving the patient's experience of IVF/ICSI: a proposal for an ovarian stimulation protocol with GnRH antagonist co-treatment

Patients undergoing IVF/ICSI frequently experience substantial treatment burden, risk and psychological distress. These three related elements contribute to a negative patient experience that can lead to treatment discontinuation if pregnancy is not achieved. One approach to minimize these factors is the use of protocols designed to achieve high term, singleton birth rates per IVF treatment started, while improving the patients welfare. Gonadotrophin-releasing hormone (GnRH) antagonists may be suitable for inclusion in such a protocol. In clinical trial data and meta-analyses, treatment with these agents is associated with similar live birth rates but reduced treatment burden (duration and side effects) and less risk of ovarian stimulation syndrome, compared with GnRH agonist long protocols. GnRH antagonists may also be associated with reduced psychological distress compared with agonists, but so far, the evidence for this is inconclusive. To facilitate the implementation of treatments that optimize the patients experience, a simple GnRH antagonist protocol for use in predicted normal responders is proposed.

High and low BMI increase the risk of miscarriage after IVF/ICSI and FET

BACKGROUND The extremes of BMI are associated with an increased risk of miscarriage both in spontaneously conceived pregnancies and after fertility treatment. The aim of the present study was to study the effect of BMI on miscarriage rate (MR) in fresh IVF/ICSI, and in spontaneous and hormonally substituted frozen-thawed embryo (FET) cycles. METHODS Analysis was carried out on 3330 first pregnancy cycles, performed during the years 1999-2004, of which 2198 were fresh, 666 were spontaneous and 466 were hormonally substituted FET cycles. A categorical, a linear and a quadratic models of the effect of BMI on miscarriage were studied by logistic regression. Factors related to patient characteristics, protocol and embryo parameters were also examined. RESULTS MR was higher in hormonally substituted FET (23.0%), compared with the fresh cycles (13.8%) and spontaneous FET (11.4%, P < 0.0001). Multivariate logistic regression revealed that the relationship between BMI and the risk of miscarriage is not linear but quadratic (U-shaped) (P = 0.01), indicating a higher risk of miscarriage in underweight and obese women. Hormonal substitution for FET was also associated with a 1.7-fold higher MR, compared with the fresh cycles (P = 0.002, 95% confidence interval 1.2-2.3). CONCLUSIONS Obese and underweight women have an increased risk of miscarriage, and hormonally substituted FET is associated with an even higher MR.

Pregnancy loss after frozen-embryo transfer—a comparison of three protocols

OBJECTIVE To compare the reproductive outcome of three protocols for frozen ET treatment. DESIGN Retrospective follow-up study. SETTING Two public clinics and one private clinic. PATIENT(S) Four thousand four hundred seventy frozen ET cycles between 2006 and 2010. INTERVENTION(S) Thawing of embryos and ET. MAIN OUTCOME MEASURE(S) Pregnancy test rate, clinical pregnancy rate, and pregnancy loss rate. RESULT(S) The natural cycle followed by P (NC + P) was used in 26% of cycles, the natural cycle with hCG (NC + hCG) in 10%, and the substituted cycle with estrogen and P (E + P) in 64% of cycles. The rate of transfers after thawing was similar in all groups (87.2%, 73.9%, and 87.2%, respectively). There was a significantly higher positive pregnancy test rate in the E + P (34.3%) and NC + hCG (35.5%) cycles as compared with the NC + P cycles (26.7%). However, the clinical pregnancy rate was similar in all groups (27.7%, 29.1%, and 24.3%, respectively). Moreover, no differences were seen between groups regarding the live-birth rate (20.1%, 23.5%, and 20.7%, respectively). A logistic regression analysis showed that the type of protocol was the only predictor of pregnancy loss, while age, irregular cycles, endometrial thickness, number, and quality of embryos transferred did not correlate to pregnancy loss. CONCLUSION(S) A higher positive pregnancy test rate was obtained in E + P frozen ET cycles in comparison with other protocols; however, due to an increased preclinical and clinical pregnancy loss, comparable clinical pregnancy, and delivery rates are reported for the three protocols.

Seasonal changes in pituitary function: amplification of midfollicular luteinizing hormone secretion during the dark season**Supported in part by grants from the Academy of Finland and the Paolo Foundation, Helsinki, Finland.

OBJECTIVE To analyze the effect of season on the pulsatility of gonadotropin secretion in women living in an area with a large annual variability in daylight length. DESIGN A prospective study. Pulse studies were carried out in each subject during both the dark and light season. SETTING The gynecologic endocrine research unit of the University Central Hospital of Oulu. PARTICIPANTS Eleven ovulatory, healthy women volunteering for the study. INTERVENTIONS Serum samples were collected at 10-minute intervals for 6 hours on days 7 to 9 of the cycle. MAIN OUTCOME MEASURES Serum LH and FSH concentrations were measured and the data were analyzed with an algorithm computer-based program. RESULTS The mean area of LH pulses analyzed was significantly higher during the dark season than the light season (49.1 +/- 3.1 versus 38.5 +/- 1.7 mIU/mL; conversion factor to SI unit, 1.00), while in the amplitude (1.9 +/- 0.1 versus 1.8 +/- 0.1 mIU/mL), number of pulses (5.2 +/- 0.3 versus 4.4 +/- 0.6), and the mean level (9.6 +/- 0.5 versus 9.4 +/- 0.9 mIU/mL) the difference did not reach statistical significance. The number (5.2 +/- 0.5 versus 5.2 +/- 0.4,), amplitude (1.0 +/- 0.05 versus 1.1 +/- 0.07 mIU/mL; conversion factor to SI unit, 1.00), area (29.9 +/- 2.4 versus 29.6 +/- 3.1 mIU/mL), and the mean level of FSH (5.4 +/- 0.6 versus 6.0 +/- 0.8 mIU/mL) during the dark and light seasons were identical, showing no seasonal variability. CONCLUSIONS The results indicate increased pituitary LH secretion in the midfollicular phase during the dark season that may be related to increased melatonin secretion and decreased ovarian activity at this time of the year.