An upper limit of gonadotropin dose in patients undergoing ART should be advocated.

AIM: As no upper limit of the daily dose of gonadotropins (DD GN) used for controlled ovarian hyperstimulation (COH) in patients undergoing assisted reproductive technology (ART) has been established, we aimed to evaluate the efficacy of using different DD GN in terms of live-birth achievement. METHODS: Data of patients treated at a single university medical center during the same period was analyzed retrospectively. Four groups were analyzed according to the DD GN administered: group I ("high dose"): >225- ≤ 375 IU; Group II ("Very high dose"): 376-450 IU; group III ("extremely high dose"): 451-600 IU. Normo-responders treated with DD GN ≤250 IU served as control (C). Variables included were DD GN, total GN dose/cycle, age, FSH, BMI, gravidity, parity, cycle number, IVF/ICSI, infertility diagnosis treatment protocol and outcome parameters. RESULTS: The analysis of 1394 treatment cycles of 943 patients indicated that DD and total dose of GN correlated negatively with the number of oocytes, implantation, clinical pregnancy and live-birth rate (25.9%, 14.6%, 11.4% and 4.7% in groups C, I, II and III, respectively) The logistic regression analysis indicated that the adjusted odds ratios for LBR correlated inversely with the DD administered - independently from age, baseline FSH, BMI and previous failed cycles. CONCLUSIONS: Increasing the daily dose of GN to doses higher than 450 IU or a total dose of 3000 IU/cycle is at least questionable if not harmful.

Serum retinol-binding protein-4 levels in polycystic ovary syndrome patients undergoing controlled ovarian hyperstimulation for in-vitro fertilization cycle.

AIMS: To determine serum retinol-binding rotein 4 (RBP-4) levels in polycystic ovary syndrome (PCOS) patients undergoing controlled ovarian hyperstimulation (COH) for an in vitro fertilization-embryo transfer (IVF-ET) cycle and the possible correlation to COH variables. PATIENTS AND METHODS: 11 consecutive PCOS patients undergoing our routine IVF flexible multidose gonadotropin-releasing hormone (GnRH)-antagonist protocol. Blood was drawn three times during the COH cycle: (1) day 1 or 2 of menstruation, and prior to gonadotropin administration (Day-S) (Day-S); (2) day of or prior to human chorionic gonadotropin (hCG) administration (Day-hCG); and (3) day of ovum pick-up (Day-OPU). Levels of estradiol and serum RBP-4 were compared among the three time points. Serum RBP-4 was measured with a commercial immunoassay. RESULTS: Results showed significantly lower levels of serum RBP-4 on Day-OPU and Day-hCG than on Day-S. Though significant correlations were observed between serum RBP-4 and body mass index, fasting glucose or glucose to insulin ratio, no correlations were found between serum RBP-4 and IVF treatment variables or pregnancy rate. CONCLUSION: While serum RBP-4 decreases during COH for IVF, there is apparently no correlation of serum RBP-4 levels with IVF treatment variables or outcome.

The possible influence of increased body mass index on the clinical efficacy of standard human chorionic gonadotropin dosage.

OBJECTIVES: To evaluate whether the efficacy of standard (10,000 IU) hCG dosage is BMI dependent. PATIENTS & METHODS: During the study period, body mass index (BMI) was recorded in 261 consecutive women enrolled in our ICSI program. Women in the 90th BMI percentile were compared with those in the 10th percentile. The number and percent of mature metaphase-II (M-II) oocytes were considered as the outcome measure. RESULTS: Mean BMI of the 10th and 90th percentile groups were 18.2 +/- 0.7 kg/m2 (n = 26) and 32.8 +/- 2.2 kg/m2 (n = 27), respectively. There were no differences between the groups in mean patients age, number of gonadotropin ampoules used, mean number of oocytes retrieved or the number and percentage of mature M-II oocytes. CONCLUSIONS: Standard (10,000 IU) hCG dosage is adequate to induce final oocyte maturation in IVF patients regardless of their BMI. This may imply that this hCG dosage is much higher than the dosage that is actually required.

Early endometrial changes following successful implantation: 2 and 3-dimensional ultrasound study.

OBJECTIVE: To study of the possible role of ultrasound (US) measurements of the endometrium in the prediction of IVF outcome. PATIENTS AND METHODS: 28 infertile women underwent US measurements of endometrial thickness and volume on day of ET and two weeks later. US measurements were compared between day of ET and two weeks later, and between those who conceived and those who did not. RESULTS: While in the group of patients who conceived (n = 7) endometrial thickness and volume rose significantly between day of hCG and two weeks later, no differences were observed in patients (n = 21) who did not. CONCLUSION: The dynamic changes in endometrial volume and thickness between day of ET and two weeks later may predict IVF treatment outcome.

Luteal phase support for patients undergoing frozen-thawed embryo transfer cycles--the required progesterone dose.

OBJECTIVE: With the recent trend toward single-embryo transfer (ET), cryopreservation of extraneous embryos is becoming increasingly prevalent. Several replacement protocols for frozen-thawed ET exist, with no consensus regarding the dosage or delivery mode of progesterone. PATIENTS AND METHODS: Hormonal replacement with only estrogen and progesterone is the most frequently used protocol in women with and without functioning ovaries in our unit. Since August 2005, we have doubled the usual daily dose of progesterone for luteal support due to a high prevalence of patients experiencing withdrawal bleeding 11-13 days after ET. We compared the outcome of frozen-thawed ET cycles using different doses of progesterone for luteal support. RESULTS: While the prevalence of embryos that survived the thawing process was significantly higher in the earlier (69%) as compared to the later period (58%), positive b-hCG pregnancy rates (17.5% vs 44.8%, respectively) and clinical pregnancy rates per transfer (7.9% vs 41.4%, respectively) were significantly higher in the later period. CONCLUSION: We conclude that high-dose progesterone supplementation in the luteal phase of frozen-thawed ET cycles results in a significantly higher clinical pregnancy rate.

GnRH agonist versus GnRH antagonist in ovarian stimulation: is the emperor naked?

OBJECTIVE: The aim of the study was to evaluate the influence of type of GnRH-analog used during controlled ovarian hyperstimulation (COH) on the outcome of in vitro fertilization (IVF) cycles. PATIENTS AND METHODS: All consecutive women aged < or = 35 years admitted to our IVF unit from January 2001 to December 2004 were enrolled in the study. Only patients undergoing up to their third IVF cycle attempt were included. Ovarian stimulation characteristics, number of oocytes retrieved, number of embryos transferred, and clinical pregnancy rate were compared between women given GnRH-agonist or GnRH-antagonist during COH. RESULTS: Four hundred and eighty-seven consecutive IVF cycles were evaluated, 226 in the agonist group and 261 in the antagonist group. A clinical pregnancy was achieved in 93 patients in the agonist group (pregnancy rate 41.2% per cycle) and 66 patients in the antagonist grup (pregnancy rate 25.3%); this difference was statistically significant (p < 0.01). The agonist group also used significantly more gonadotropin ampoules, required longer stimulation, and had higher estradiol levels on the day of human chorionic gonadotropin administration. CONCLUSION: The midluteal long GhRH-agonist suppressive protocol should be the protocol of choice in young patients in their first three IVF cycle attempts.

Does pregnancy affect medical ethical decision making?

OBJECTIVE: We studied and compared the attitudes of pregnant women v new mothers in an attempt to confirm changing patterns of maternal response towards medical ethical decision making in critically ill or malformed neonates. DESIGN: Data were obtained by questionnaires divided into three sections: 1. sociodemographic; 2. Theoretical principles which might be utilised in the decision-making process; 3. Hypothetical case scenarios, each followed by possible treatment options. RESULTS: Pregnant women (n = 545) consistently requested less aggressive medical intervention for the hypothetical cases than did new mothers (n = 250) [Trisomy 18: 57% v 42%; p = 0.0004; Asphyxia: 75% v 63%; p = 0.0017; Down's syndrome 81% v 62%; p = 0.0001; LBW 85% v 75%; p = 0.004]. Significant differences were also observed in the responses to the theoretical principles, with pregnant women attributing less importance to preserving life at all cost, while being more concerned with physical and emotional pain and suffering, with financial cost, and with the infant's potential for future productivity.