Volume 11, Issue 3 (5-2013)                   IJRM 2013, 11(3): 243-0 | Back to browse issues page

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Azargoon A, Bahrami M, Alavy Toussy J. Comparing clomiphen citrate plus HMG with clomiphen citrate plus rFSH in IUI cycles in couples with unexplained ormale factor infertility: A prospective randomized study. IJRM. 2013; 11 (3) :243-0
URL: http://journals.ssu.ac.ir/ijrmnew/article-1-396-en.html
1- Department of Infertility, Amir-AL-Momenin Hospital, Semnan University of Medical Sciences, Semnan, Iran , azarmona2003@yahoo.com
2- Department of Infertility, Amir-AL-Momenin Hospital, Semnan University of Medical Sciences, Semnan, Iran
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Homologous intra uterine insemination (IUI) preceded by controlled ovarian hyperstimulation (COH) is a less expensive and invasive treatment than other assisted reproductive techniques. It is the best first line treatment and the most effective procedure for unexplained and male factor subfertility (1). Several studies suggest that IUI cycles with ovarian stimulation improves the probability of conception in couples with unexplained infertility but the main concern is the efficacy of the agent which has been used for stimulation (2-7). Hyper stimulation with clomiphen citrate (CC) was shown to be the cost-effective treatment for unexplained infertility, although the use of gonadotropin seemed to be a more efficatious option in IUI treatment (8).
Although several drugs with different hormone content and characteristics were available, there was no clear evidence for a superior effect according to the type of gonadotropine used in IUI cycles (9). During the past decade the production of rFSH has been considered as a milestone in the endocrine research, particularly in the field of human reproduction. The urinary preparations of gonadotropins have been progressively replaced by recombinant products which have many advantages including; independency from urine collection, ensuring a constant supply and guaranteeing batch-to-batch consistency but they had higher medical costs (10). A few investigations have prospectively compared recombinant FSH with HMG or uFSH with or without GnRH-agonist down regulation for ovarian stimulation in IUI cycles (10-13).
On the other hand, the choice of using gonadotropin is authority- based, and the best gonadotropin regimen that achieves the highest pregnancy rates in IUI cycles is also controversial (11). Considering the fact that controlled ovarian stimulation (COS) with CC plus HMG is routinely used in many infertility centres in Iran for ovarian stimulation in IUI cycles, while recombinant FSH is currently considered by many investigators as superior to human derived gonadotropins; we decided to do the first comparative study of the outcomes of CC plus rFSH protocol versus CC plus HMG protocol among a group of Iranian patients with unexplained or male factor infertility in IUI cycles.
Materials and methods
One hundred fifty women were eligible but 6 women refused to participate in the study, so we recruited 144 women with unexplained or male factor infertility undergoing IUI cycles. The selected patients allocated to case and control groups by using systematic randomization. The first patient selected as case by chance using EpiInfo software (WHO and CDC, version 6.4) and the second one to the control group and this approach continued for the rest of patients. Finally 72 patients were allocated to group 1 (CC plus rFSH group) and 72 patients to group 2 (CC plus HMG group) (figure1). The study designed as a single blind clinical trial (the research personels were not informed of the study-group assignment). The study was performed in Amir-Al-Momenin university hospital from October 2006 to June 2010. Ethical committee approval was obtained from the Research Ethics Committee of Semnan University of Medical Sciences before starting the research. All patients provided written informed consent after the methods were fully explained by a nurse.
Patients were included in the study if they satisfied the following criteria: history of infertility of more than 1 year, women’s age between 20 and 40 years old with their first IUI cycle at the time of study, documentation of normal ovulatory cycles, normal TSH and prolactin level, normal reproductive hormones in the early follicular phase, having patent tubes shown by HSG or laparoscopy and having a normal sperm count, motility and morphology according to the World Health Organization (WHO 1992) criteria for unexplained infertility and the total motile sperm count being more than 1 million in male factor infertility.
Patients with a history of renal or liver failure, cardiovascular disease and diabetes were excluded. Patients were then randomly assigned to two groups; group 1 received CC plus rFSH (Gonal F, Serono, Turkey; costing $17 per 75 IU ampoule) and group 2 received CC plus HMG (Merional, HP, Serono, Turkey; costing $10 per 75 IU ampoule). Ovarian cycle stimulation was started on the 3rd day of menstruation after the basal transvaginal ultrasound (TV-US) with 100 mg CC for 5 consecutive days. The gonadotropin regimens adopted in each group were rFSH 75 IU for group 1, subcutaneous, daily and HMG 75 IU for group 2, intramuscular, daily from day 7 of menstrual cycle (150 IU for woman≥35 years old).
TV-US was started from day 9 of menstrual cycle every other day for follicular size tracing. The gonadotropin dose was continued until the occurrence of at least one dominant follicle (ovarian follicule ≥16 mm in diameter), then HCG (Profasi, Serono, Turkey) 10'000 IU was administered intramuscularly to trigger final follicular maturation and IUI with a sperm swim-up procedure was performed 35-36 hours later. For the prevention of ovarian hyperstimulation syndrome (OHSS), ovulation was induced by busereline acetate (0.5 mg subcutaneously) if there were ≥5 follicles with a diameter of ≥16 mm on the day of HCG administration. The luteal phase was supported by 400 mg of vaginal progesterone suppository (Cyclogest, Actavis, UK) administered twice a day from the day of IUI for two weeks.
A blood sample for beta human chorionic gonadotropin (βhCG) was obtained two weeks after IUI for pregnancy confirmation. A clinical pregnancy was determined by the visualization of an embryo with cardiac activity at 7 weeks of gestation in TV-US. In case of pregnancy progesterone was continued till 12 weeks of gestation. The primary outcome measures were clinical and ongoing pregnancy rates. The total rFSH and HMG
doses, the number of treatment days, the number of mature follicles, the mean size of mature follicles and the endometrial thickness on the day of HCG administration were secondary outcomes.
Statistical analysis
We used PASW (Version 18, © IBM SPSS Inc.) for entering data, calculating descriptive results and performing statistical