José Serna

Estradiol supplementation during the luteal phase of IVF-ICSI patients: a randomized, controlled trial

OBJECTIVE To evaluate the effectiveness of transdermal E(2) administration in the luteal phase of IVF/ICSI cycles. DESIGN Prospective, open-label, randomized clinical trial. SETTING University-affiliated assisted reproduction center. PATIENTS 1) Pilot trial to test serum E(2) behaviour during the luteal phase in women undergoing agonist as well as antagonist protocol; 2) women undergoing IVF/ICSI with good-quality embryos available. INTERVENTION(S) One hundred seventy-six patients were randomized by random number list on the day of embryo transfer to either: 1) progesterone (P) only as luteal support (200 mg bid starting the following night after oocyte retrieval); or 2) E(2) and P combined, applying E(2) patches (100 microg/day) twice per week beginning on the day of embryo transfer with P, as in the P-only group. MAIN OUTCOME MEASURE(S) The primary outcome was implantation rate per embryo transfer; secondary outcome variables were pregnancy rate per embryo transfer, early pregnancy loss, multiple pregnancy rate, and midluteal P and E(2) levels. RESULT(S) Hormonal levels did not differ between groups. There were no statistically significant differences in terms of implantation rate (34.9% [51 of 146] vs. 28.9% [41 of 142]), ongoing pregnancy rate 42% ([34 of 81] vs. 41.8% [33 of 79]), early pregnancy loss (15% [6 of 40] vs. 13.2% [5 of 38]), or multiple pregnancy rate (28.6% [12 of 42] vs. 24.4% [10/41]) in patients receiving P versus E(2) + P. CONCLUSION(S) The addition of transdermal E(2) to the luteal-phase P support of IVF cycles did not improve cycle outcomes in terms of implantation and pregnancy rates.

Effect of repeated assisted reproduction techniques on the ovarian response.

Purpose of review Despite the increasing success of assisted reproduction techniques, most couples need more than one cycle of controlled ovarian hyperstimulation to achieve a pregnancy. The effect of several cycles on the ovarian response in subsequent cycles is a concern for gynaecologists and patients. In addition, egg donors have the possible risk of an ovarian reserve decrease. In this review, we present published evidence on the effects of repeated assisted reproduction techniques on the ovarian response. Recent findings Recent available data indicate that ovarian response persists with subsequent cycles of controlled ovarian hyperstimulation in terms of oocytes being retrieved, although it is not clear whether an increased level of gonadotropins is required to achieve this response. There is a decrease in the number of oocytes retrieved in subsequent cycles due to increased female age as more cycles are needed. The oocytes retrieved in one cycle seem to come from the antral pool that otherwise would be atretic due to dominant follicle selection. Summary The mechanisms involved in the recruitment from atresia of more than one follicle are discussed and it is shown that repetitive ovarian stimulation does not appear to affect the ovarian reserve. Published evidence shows that gonadotropins alter the physiologic selection of one single dominant follicle but do not accelerate the recruitment of follicles from further cycles, confirming that there is no detrimental effect on ovarian function after repetitive controlled ovarian hyperstimulation.

Pros and cons of implementing a carrier genetic test in an infertility practice.

Purpose of review Carrier screening is promptly evolving thanks to the rapid development of new technologies and mutation knowledge. Expanded carrier screening is already being used in assisted reproduction. Medical, ethical, psychological and legal aspects appear from the general public, patients, healthcare providers and scientific societies. Pros and cons of implementing this technique are highlighted. Recent findings Recent publications show the development of wider gene screening panels with lowering cost. Human genome is continually being updated as are the number of mutations and their corresponding phenotype known. Classical criteria established to consider a genetic screening protocol are nowadays overtaken, and scientific societies are developing guidelines and criteria adapted to expanded genetic testing. There is no universal agreement on the mutations that should be included in the panel. Patients’ perceptions on carrier genetic testing seem to be positive. Counselling patients is of paramount importance stressing implications when testing positive on their clinical decision making. Gamete donor genetic testing implies a modified approach and blinded matching must be offered. Summary There are important positive aspects implementing a carrier genetic test in assisted reproductive technique, but controversial issues appear. Reproductive providers must be appropriately aware and follow the new guidelines.

Pancreatic autoimmunity: An unknown etiology on patients with assisted reproductive techniques (ART)-recurrent reproductive failure

Pancreatic Autoimmunity is defined as the presence of autoantibodies and more frequent need for insulin treatment. Affected women presenting recurrent implantation failure (RIF) or recurrent miscarriage (RM) are often misdiagnosed. The objective of thestudy was to describe clinical and metabolic profiles suggestive of Pancreatic Autoimmunity and therapeutic strategy in patients with RIF/RM. We analyzed retrospectively 735 patients, and have identified a subset (N = 20) with similar metabolic characteristics. At the same time, we included a control group (n = 39), with similar demographic characteristics and negative for pancreatic, thyroid or celiac disease autoimmunity. The patients identified with autoimmune metabolic problem (N = 20) had relatives with diabetes mellitus. At 120 minutes after Oral Glucose Tolerance Test (OGTT) low level of insulin secretion (<2 IU/ml) was found in 70% of patients. Glutamic acid decarboxylase 65 (GAD 65) antibodies, with or without other autoantibodies, were positive in80% of patients and anti-IA2 alone were positive I the rest. Since pregestational period, insulin administration was recommended for 10 patients, metformin for 4 patients and exclusively diet control in 5 of them. Significantly increased live bith rates (LBR) per cycle were observed after metabolic control (52%) compared with live birth rate (LBR) after cycles without control (7.5%) (p<0.0001). We noticed 2 cases of pre-eclampsia and 6 low-birth weights. Insulin administration was needed during the pregnancy in 68% of patients and after childbirth in 31.57% of them. In our control group, all of patients (n = 39) underwent ART (53.8% SET and 46.1% DET) with a 50% (SET) and 61.9% (DET) live birth rate (LBR) per cycle. Patients with RIF/RM, normal BMI, low insulin levels after OGTT could benefit from additional metabolic immune testing. A correct diagnosis and treatment could have a positive impact on their reproductive results and live birth rate.