Assessment of the value of ultrasound monitoring and doubling of insemination in clomiphene citrate stimulated IUI cycles

Objective: To compare the results of controlled ovarian stimulation and intra-uterine insemination using 4 protocols. Design: Prospective non randomized study. Setting: An assisted reproduction unit in a private hospital. Materials and methods: 91 couples with unexplained infertility and 79 couples with male subfertility. All women received clomiphene citrate 50 mg twice daily starting from the 3rd day of cycle for 5 days. Patients were classified into 4 groups. The 1st group (45 patients, 125 cycles) was monitored by transvaginal sonography. HCG was given when at least one follicle reaches a diameter of 17 mm or more. IUI was scheduled 36 hours after the HCG shot. The 2nd group (43 patients, 118 cycles) was also monitored by ultrasound and HCG was given as before, double insemination was done 20 hours and 40 hours after the HCG shot. In the 3rd group (42 patients, 112 cycles), monitoring of ovulation was done using commercial urinary LH detection kit, IUI was scheduled 24 hours after detection of LH. In the 4th group (40 patients, 108 cycles), monitoring of ovulation was done by urinary LH detection kit, double insemination was done 12 and 24 hours after detection of LH. Main Outcome measure: Clinical pregnancy rate (PR). Results: A total of 170 patients underwent 463 cycles with an average of 2.72 cycles per patient. The total number of pregnancies was 31 with an overall PR of 18% per patient and 7% per cycle. The overall pregnancies for groups I, II, III, and IV were 8 (18% per patient, 6% per cycle), 9 (21% per patient, 8% per cycle), 7 (17% per patient, 6% per cycle), and 7 (18% per patient, 6% per cycle), respectively. There was no statistically significant difference between any two groups. Patients with unexplained infertility and patients with infertility duration of less than 4 years had significantly higher PR than patients with male subfertility and patients of infertility duration more than 4 years respectively. Conclusion: Clomiphene citrate (CC) stimulated IUI cycles, self monitored by urinary LH kits and employing single insemination, appear to be a simple, relatively effective and inexpensive initial management for couples with unexplained infertility or mild male factor subfertility of less than 4 years duration. Controlled ovarian stimulation together with intrauterine insemination (COS/IUI) is a widely used practice for the management of infertility, particularly for couples with unexplained infertility, male factor infertility, or endometriosis (1-3). COS Consultant of obstetrics and gynecology SGH-Aseer, Lecturer of obstetrics and gynecology, Kasr El-Ini, Cairo University. Consultant of clinical pathology SGH-Aseer, Assistant Professor of clinical pathology, Ain Shams University. plus IUI has been found to be more effective for treatment of infertility than either treatment alone (2, 4). Several studies documented that COS/IUI treatment is cost effective for subfertile couples before proceeding to the more invasive and expensive IVF procedures (1, 5). COS using clomiphene citrate (CC) is relatively simple, inexpensive, and safe. The PR per cycle in CC/IUI cycles varies from 6-26% (2, 3, 6). CC has been found to be as effective as gonadotropins for COS Middle East Fertility Society Journal Vol. 9, No. 1, 2004 Copyright © Middle East Fertility Society Vol. 9, No. 1, 2004 Azab and Afify U/S monitoring and doubling of insemination in CC stimulated IUI cycles 31 Table 1. Summary of patients' characteristics. Group I Group II Group III Group IV Statistics Number of patients 45 43 42 40 Number of Cycles Mean (SD) Range 125 2.78(0.56) 2-4 118 2.74(0.54) 2-4 112 2.67(0.53) 2-4 108 2.70(0.52) 2-4 NS Age (years) Mean (SD) Range 29(2.5) 25-36 28.3(2.1) 24-35 28.2(2.3) 24-34 29.1(2.8) 25-37 NS Infertility Duration Mean (SD) Range 4(1.2) 2-6 3.9(1.2) 2-6 3.8(1.1) 2-5 4(1.3) 2-7 NS Infertility Etiology Unexplained Infertility Male subfertility 23 22 23 20 24 18 21 19 NS NS (Non Significant) in certain population of patients (7). In this study, we are trying to reach a simple and inexpensive protocol as an initial management of infertile couples. We are investigating the value of monitoring of ovulation using vaginal ultrasound versus self monitoring using urinary LH detection kits, at the same time we are checking the value of double insemination versus single insemination. MATERIALS AND METHODS Ninety one couples with unexplained infertility and 79 couples with male subfertility participated in this study during the period from April 2001 until December 2002. The hospital review board approved the protocol of the study. An informed consent was taken from the couples. The age of female partners ranged from 24-37 years with a mean of 28.5 years. All couples had at least 2 years duration of infertility. They had undergone the basic infertility evaluation including history, clinical examination, mid luteal phase progesterone, prolactin assay, and semen analysis. Tubal patency was confirmed by either hysterography or laparoscopy. Women with tubal abnormality were excluded from the study. Unexplained infertility was considered if the results of basic infertility evaluation were normal. Male factor infertility was defined as sperm count < 20 millions/ml, normal morphology < 30 %, or progressive motility < 50 % before sperm preparation. Subjects' characteristics are summarized in Table 1. All women received CC 50 mg tablets twice daily for 5 days starting from the 3rd day of cycle. Women were classified into 4 groups. There was no significant difference among the 4 groups regarding, the age, the duration of infertility, the number of cycles per patient, or the distribution of patients with unexplained infertility and male infertility. In the 1st group monitoring of ovulation was done using transvaginal sonography (TVS) starting from the 10th day of cycle. HCG 10,000 IU was given when the mean diameter of at least one follicle is ≥ 17 mm. Single insemination was then done 36 hours after the HCG shot. The 2nd group was also monitored by TVS and HCG was given as before. Two inseminations were done 20 and 40 hours after the HCG shot. In the 3rd group monitoring of ovulation was done using urinary LH detection kits (Clear Plan) starting from the 10th day of cycle, single insemination was done 24 hours after detection of LH surge. The 4th group was monitored by LH detection kit and double insemination was done 12 and 24 hours after detection of LH surge. The choice of treatment for each couple was based on their 32 Azab and Afify U/S monitoring and doubling of insemination in CC stimulated IUI cycles MEFSJ Table 2. PR according to cause of infertility Unexplained infertility Male subfertility Chi square P value PR/Patient 21/91 (23%) 10/79 (13%) 2.33 0.13(NS) PR/Cycle 21/245 (9%) 10/218 (5%) (NS) Non Significant preference. The same method was used if the couple had more than one cycle of treatment. Male partners were instructed to collect semen by masturbation after 2-4 days of sexual abstinence. After liquefaction and initial semen analysis, suitable samples were prepared using the density gradient method. SupraSperm system from Medi-Cult (Copenhagen, Denmark) was used. 2 ml of the 55% SupraSperm were dispensed in a centrifuge tube, and then 2 ml of the 80% supraSperm were dispensed beneath the 1st solution. 1 ml of semen sample was added to the prepared gradient. The tube was then centrifuged for 20 minutes at 300g. The supernatant was carefully removed leaving the sperm pellet. The pellet is suspended in 2 ml sperm preparation medium (Medi-Cult) and Centrifuged for 10 minutes at 200g The supernatant was removed and the wash process was repeated. The pellet is then suspended in 0.5 ml of sperm preparation medium. If the count of motile sperms after preparation was less than 5 millions, these couples were excluded from the study and referred to either IVF or ICSI. IUI was done using Wallace (Wallace, Kent, U.K.) IUI catheters, with 1 or 2 ml syringe. With the patient in lithotomy position a speculum was inserted in the vagina. The cervix was cleaned by cotton swab. The IUI catheter was gently passed through the cervical canal. 0.5-2 ml of sperm Table 3. PR according to infertility duration