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Irisin is a novel myokine and adipokine which induces an increase in total body energy expenditure, improving insulin sensitivity and glucose tolerance in experimental animals. In the present study, serum irisin concentration was measured by an enzyme immunoassay in 130 women with gestational diabetes mellitus (GDM) and 140 BMI-matched patients with normal glucose tolerance (NGT). Median irisin level was significantly lower in the patients with GDM than in the NGT subjects (1703.3 [1354.8-2097.9 ng/ml] versus 1873.8 [1519.8-2294.8 ng/ml], p = 0.01); however, 3 months after childbirth its concentrations did not differ markedly between the two groups (1165.9 [872.1-1497.5] ng/ml versus 1139.0 [984.0-1376.7] ng/ml). In the whole group, irisin concentration correlated negatively with 2 h glucose level (R = -0.14, p = 0.03). In the women with NGT, irisin concentration correlated positively with IS(OGTT) (R = 0.22, p = 0.04) and the disposition index (DI(120)) (R = 0.24, p = 0.03), as well as negatively with 2 h insulin level (R = -0.23, p = 0.03) and HOMA-IR (R = -0.24, p = 0.02). Multiple regression analysis revealed that 2 h glucose and DI(120) were the only variables significantly influencing serum irisin (β = 0.158, p = 0.03 and β = 0.159, p = 0.02, respectively). Our results suggest that serum irisin concentration increases markedly in pregnant women, but this increase seems to be significantly lower in patients with GDM.

One hundred and twelve severely overstimulated in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) patients were treated with coasting when estradiol concentration was3000 pg/ml and the leading follicles had attainedor = 18 mm in diameter. Gonadotropin withholding was offered to them as a promising method for the prevention of both cycle cancellation and complications associated with severe ovarian hyperstimulation syndrome (OHSS). The duration of prolonged coasting prior to human chorionic gonadotropin (hCG) administration ranged from 2 to 9 days (mean 3.5). hCG was administered when the serum estradiol dropped to3000 pg/ml and at least three growing folliclesor = 20 mm in diameter were present. Fertilization failure was noted in six couples and in another 10 cases freezing of all embryos was decided, therefore embryo transfer was performed on 96 patients. There were 31 clinical pregnancies (five twins) giving a pregnancy rate per patient and per embryo transfer of 30.4% and 32.3%, respectively, with an implantation rate of 18.1%. With regard to all 112 coasted patients, six developed moderate and two severe OHSS. This study shows that withholding gonadotropin administration in high-risk IVF patients results in a good cycle outcome and a very low risk of severe OHSS, and also demonstrates the importance of both the timing of coasting initiation and the timing of hCG administration.

In a prospective study, we compared two protocols of ovulation stimulation, the clomiphene citrate and human menopausal gonadotropin (hMG) versus D-triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist and hMG in 324 couples having their first in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) program, in terms of pregnancy rates and cost-effectiveness of drugs used. The GnRH agonist/hMG group was characterized by a greater mean number of ampoules of hMG used (31.7 versus 10.2), a larger number of oocytes collected (10.4 versus 4.2), and a larger number of embryos obtained (5.8 versus 2.9). With the policy of transferring only two of the best quality embryos, the mean number of embryos replaced were comparable (1.8 in clomiphene citrate/hMG and 1.9 in GnRH agonist/hMG group). The percentage of patients reaching embryo transfer was lower in the clomiphene citrate/hMG than in the GnRH agonist/hMG group (84.1% versus 93.1%, respectively). However, the combined results of the IVF and ICSI procedure in terms of pregnancy rate, both per patient and per embryo transfer were better, though not significantly in the clomiphene citrate/hMG than in GnRH agonist/hMG group (25.0% and 29.7% versus 23.7% and 25.5%, respectively). Similarly, the implantation rate was better (19.0% versus 13.5%, respectively). With the use of clomiphene citrate/hMG, a fivefold less costly drug regimen, we obtained pregnancy rates equivalent to those gained using GnRH agonist/hMG in our IVF/ICSI program.

Age is often a dominant factor for women wanting to conceive. The objective of this study was to examine the outcome of an in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) program in relation to a woman's age. Between January 1995 and June 1997 we stimulated 2511 cycles. The mean age of the women was 34 years, with 21.9% under 30, 45.9% between 30 and 35, 24.5% between 36 and 39, and 7.7% over 39 years. All patients agedor = 40 years had day 3 serum follicle-stimulating hormone (FSH) concentrations20 IU/l. The stimulation regimen consisted of 150-450 IU of human menopausal gonadotropin (hMG) or FSH combined with either clomiphene citrate (CC) or gonadotropin-releasing hormone agonist (GnRHa) in a short or long protocol. Age had a significantly negative effect on the stimulation and fertilization failure rates. The clinical pregnancy rate per transfer and the embryo implantation rate declined significantly from 29.4% and 18.9% in women30 years to 19.8% and 14.3% in patients between 30 and 35 years, 17.1% and 9.0% between 36 and 39 years and to 12.8% and 7.4% in those agedor = 40 years. The spontaneous abortion rate was 14.9%, 16.5%, 22.4% and 33.2%, respectively. The clinical pregnancy rate per transfer reflected only imperfectly the performance of the older women because the discharge rate during stimulation and spontaneous abortions reduced the 'take home baby' rate to about 7% per cycle in patients agedor = 40 years. It is very important in fertility practice to recognize the major impact of advancing maternal age.

The aim of this study was to assess the benefits of the transfer of only two of the best quality embryos, three if a woman was over 35 years of age, in terms of pregnancy rate and the incidence of multiple gestations. In 1993-94, when we were replacing three embryos when available and up to five when the woman was over 35 years of age, 217 clinical pregnancies were obtained (25% per embryo transfer). Among them there were 34 (15.6%) twins and 8 (3.7%) triplet pregnancies. Eighty-one patients had surplus embryos cryopreserved. In 1995, with the new policy of transferring only two embryos and three when the woman was over 35 years of age, 170 patients became pregnant (23.9% per embryo transfer). There were 31 (18.2%) twins and no triplet pregnancies. One hundred and forty-four patients had surplus embryos cryopreserved. Although limiting the number of transferred embryos slightly decreases the pregnancy rate, this small reduction can be considered acceptable if the social, health and financial problems associated with high-order multiple gestations are taken into account.

The objective of this study was to examine the efficacy of D-triptorelin in the long protocol and follicle-stimulating hormone (FSH) in an IVF-embryo transfer program in a group of patients with polycystic ovary syndrome (PCOS) who had earlier failed to respond or did not conceive after clomiphene citrate (CC)/human menopausal gonadotropin (hMG) or 'flare up' gonadotropin-releasing hormone agonist (GnRHa)/hMG stimulation. Eighty-nine women with PCOS (based on typical ultrasound criteria) had 1-3 treatment cycles without success. The stimulation protocol was changed to D-triptorelin given in midluteal phase and when pituitary desensitization was achieved, FSH administration was started. The clinical pregnancy rate per transfer in this 'negatively selected' group of PCOS patients was 29%. This was the same as the rate for a group of women with tubal factor, as was the spontaneous miscarriage rate. Although the use of GnRH agonists in the long protocol increases the costs of treatment, the number of cancelled cycles is reduced. The pregnancy rate increased in this group of women with PCOS.

A total of 32 patients undergoing in vitro fertilization (IVF) and 16 treated for ovulatory disturbances were stimulated with clomiphene citrate and human menopausal gonadotropin. Gonadotropin releasing hormone (GnRH) analog was used for induction of the ovulatory surge of gonadotropins, because of the risk of ovarian hyperstimulation syndrome. In four patients after IVF–embryo transfer and four patients after ovulation induction, single pregnancies were obtained. None suffered from ovarian hyperstimulation syndrome. The authors suggest that the use of GnRH analog for induction of the gonadotropin ovulatory surge prevents the development of ovarian hyperstimulation syndrome.

Gonadotropin-releasing hormone (GnRH) agonists are increasingly used in ovarian hyperstimulation protocols in in vitro fertilization (IVF) programs. From March 1992 to June 1993, 565 patients attending our Institute underwent superovulation in 1104 IVF program cycles. Of these cycles, 650 were stimulated with clomiphene citrate and gonadotropins (human menopausal gonadotropin/hMG), and 454 with the GnRH agonist buserelin and hMG in a group of patients who had earlier failed to respond or did not conceive after clomiphene citrate/hMG stimulation. The ovarian response was similar in both groups, however, with the use of buserelin more oocytes were recovered -4.9 +/- 3.2 and 3.5 +/- 2.3 oocytes, respectively. The clinical pregnancy rate per transfer in the group of patients superovulated with buserelin/hMG was twice that of the clomiphene citrate/hMG group (21.0% vs. 10.4%). The relatively high pregnancy rate with the buserelin/hMG regimen in the group of 'poor responders' may be connected with GnRH agonist-induced pharmacological hypophysectomy and the sequelae thereof: normalization of some endocrinopathies, absence of an endogenous luteinizing hormone (LH) surge and better endometrium receptivity, oocytes and embryo quality.

Uterine septum is the major intrauterine disorder associated with infertility and recurrent abortions. The aim of the study was to find out what is the effectiveness of hysteroscopic intrauterine septum resection in terms of reproductive outcome and in comparison with conventional procedure. The mean follow up period was 18 +/- 8.3 months. The pregnancy wastage before operation in study group was 79% and decreased to 45% after hysteroscopic treatment. Hysteroscopic resection of intrauterine septum is the treatment of choice for patients suffering from infertility or recurrent pregnancy wastage.