Polycystic ovarian syndrome (PCOS) is one of the most common causes of endocrine disorders and main reasons forinfertility due to unovulation and recurrent abortions (
This stratified cohort study was conducted over a period of one year (2009) on 38 infertile women with PCOS who were suitable candidates for the IVF program. All cases were between ages 20 to 38 years. Patients were evaluated for other causes of infertility by hysterosalpingography (HSG) and laparoscopy. Their partners' sperm analyses, according to WHO guidelines (2002) were all normal. The criteria for selection of PCOS patients were based on: i. history of amenorrhea or oligomenorrhea; ii. hyperandrogenism (i.e., hirsutism >7 according to Ferriman Gallweg score ; iii. elevated LH or LH/follicle stimulating hormone (FSH) >2; and iv. increased ovarian volume >9 ml or antral follicle count ≥10 as seen with ultrasound.
All patients underwent the long pituitary down regulation protocol. They were given low doses of oral contraceptives (OCP) on the third day of menstruation. On days 20 to 21 of their menstrual cycles (late luteal phase), a GnRH agonist (Suprefact, Hoechst, Aquila, Italy) at 500 ìg/day, sub-cutaneous injection was begun.
After two weeks of Suprefact injections, on the third day of the next menstrual cycle, serum estradiol levels were checked and a vaginal sonographic scan was performed to confirm pituitary suppression. Induction ovulation was started in cases where: i. serum estradiol levels were <50 pg/ml, ii. there was no cyst or follicle >10 mm, and iii. the endometrial thickness was <4 mm. Otherwise, GnRH agonist would be given for an extra week, for up to 21 days. On the third day of menstruation, 150-225 units of gonadotropin[rFSH (gonal-F; Serono, Aubonne, Switzerland)] was administered according to age, weight, and FSH levels. Suprefact was decreased to half of its initial dose on that day. After administrating gonal-F for 5 days, ovarian response was monitored by vaginal ultrasound; then gonal-F was regulated. When there were at least two 18 mm follicles, hCG (Profasi, Serono, Rome, Italy) at a dose of 10000 IU was injected. The progesterone level was checked on the day of hCG injection. Oocyte pickup was performed 36-38 hours later. After a period of 48 hours, embryo transfer with a Cook catheter (Cook catheter OB/GYN spencer JN) was performed. There were between 2-4 embryos that were transferred, dependent upon the embryo age and quality. Luteal phase support was carried out by progesterone injection, 100 mg per day from the oocyte retrieval day.
Subjects were selected through interviews, examinations, and lab tests. Upon receiving information, all subjects consented to participate in the study. According to serum progesterone levels on the day of hCG injection, patients were divided into 2 groups of: i. <1.2 ng/ml or ii. >1.2 ng/ml. Clinical pregnancy was defined as detection of the fetal heart by ultrasound at 6-8 weeks gestation Chemical pregnancy was defined as ß hCG levels >200 IU. The rate of pregnancy was compared between the two groups. The experimental data were then compared against Fisher’s exact test (SPSS, version 18). The level of significance was considered based on the criteria of p<0.05. This survey was conducted as an obstetrics and gynecology educational thesis at Tehran University of Medical Sciences and patients incurred no charges.
A total of 38 PCOS patients participated in this study. Of these, 30 (78.9%) had primary infertility. The mean infertility duration was 8.7 ± 3.5 years and mean age of the patients was 34.7 ± 4.5 years. Mean basal serum FSH level was 7.4 ± 2.6 mIU/ mL and E2 level was 59.2 ± 30.8 pg/mL.
The mean total dosage of gonadotropin used was 1950.8 ± 500.0 IU mean duration of induction was 13.1 ± 2.2 days. The mean number of oocytes was 10.4 ± 2.2 and mean total number of embryos was 8.2 ± 2.8.
Overall, the pregnancy rate in this study was 10 (26.3%). As stated earlier, the 38 PCOS patients considered for this study were divided into 2 groups based on progesterone levels on the day of hCG injection in IVF cycles. The findings of this experiment are summarized in table 1.
Comparison of pregnancy outcome in PCOS patients according to progesterone level
|Group / pregnancy result||Pregnancy rate||Clinical pregnancy||Chemical pregnancy|
|3 (15.8%)||1 (5.3%)||2 (10.5%)|
|7 (36.84%)||4 (21.1%)||3 (15.8%)|
This study showed that clinical and chemical pregnancy outcomes in PCOS patients with progesterone levels above 1.2 ng/ml were higher than those whose levels were less than 1.2 ng/ml. However, no significant statistical differences were found.
In two separate studies, Hoffman et al. (
It appears that the results of various studies are in fact quite different. These observations or contradictory reports are related to many factors that affect IVF outcome. Induction ovulation is one factor which influences the quality of oocytes and implantation. Therefore, evaluation of serum progesterone levels before oocyte aspiration is complicated. Age, predisposing factors for IVF, and numbers of embryos also change IVF cycle results. The level of serum progesterone selected in various studies is not unanimous and therefore may affect the results.
In conclusion, we recommend studies with more patients, taking into account the bias variable.