الفهرس 
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Abstract
Polycystic ovarian syndrome (PCOS) is a prevalent endocrine condition that affects women of reproductive age. It is characterized by anovulatory cycles, which account for 70% of cases of anovulation in this population (Deans, 2019). It is distinguished by excessive levels of male hormones, irregular ovulation, and changes in the appearance of the ovaries, as described by Dumesic et al. (2015). The diagnosis of Polycystic Ovary Syndrome (PCOS) is established when an individual exhibits a minimum of two out of the three specified criteria as outlined in the Rotterdam Criteria of 2004. 1. Menstrual cycle irregularities, 2. Excessive levels of male hormones, 3. Polycystic ovary with distinct morphological features as observed through vaginal ultrasonography. Clomiphene citrate is the preferred medication for treating polycystic ovary syndrome (PCOS). Clomiphene resistance is a phrase used to describe the condition where 15% - 20% of patients are unable to ovulate even after taking the full dose of clomiphene (150 mg) daily for 5 days, commencing from the 2nd or 3rd day of their menstrual cycle, for a period of 3 – 6 months (Balen, 1999). Since 1990, Gonadotropin-releasing hormone (GnRH) antagonists have been employed to inhibit pituitary functions and avoid early increases in LH levels during controlled ovarian hyperstimulation (Hall, 1988). In addition, it has been observed that GnRH antagonists have a failure rate of around 1 - 8% in effectively suppressing premature LH surges in individuals who have a normal ovarian response (Zhang et al., 2018).
Progestin primed ovarian stimulation has demonstrated the ability to extend the follicular phase by one day and result in larger pre-ovulatory follicles compared to patients undergoing a natural cycle. The studies demonstrate that progestin therapy effectively inhibits follicular rupture and extends the timeframe for oocyte retrieval (Chen et al., 2017). This study is designed to assess the effectiveness of progestin primed ovarian stimulation compared to GnRH antagonist in patients with clomiphene resistant PCOS who are undergoing ICSI cycles. The study will focus on evaluating the impact of these two approaches on the clinical pregnancy rate and premature LH surge. This study comprised a cohort of 100 individuals who exhibited clomiphene resistance or had treatment failure for polycystic ovary syndrome (PCOS). All patients who meet the specified inclusion criteria will be enrolled in this study. These criteria include being between the ages of 20 and 40 years old. 2. The patients were diagnosed with polycystic ovary syndrome (PCOS) that did not respond to treatment with clomiphene.
All participants who participated in this trial will be randomly assigned to one of two groups:
group (I) comprises 50 patients who will undergo progestin primed ovarian stimulation protocol, whereas group (II) consists of 50 patients who will undergo GnRH antagonist protocol. On the third day of the menstrual cycle, a blood sample was taken from all patients to measure basal levels of FSH, LH, Prolactin, and TSH using a chemiluminescence assay. Additionally, we will assess the levels of LH, E2, progesterone, and endometrial thickness on the day after hCG injection. Vaginal ultrasound was used to monitor follicular growth in all patients from both groups. Once the dominant follicles reached a diameter of 18-20 mm, the final stage of oocyte maturation was induced by a subcutaneous injection of 100 µg Triptorelin (Decapeptil 0.1 mg/ml subcutaneous; Ferring Pharmaceutical company, Saint-Prex Switzerland), along with 5000 IU of HCG (Choriomon; Lyophilized human chorionic gonadotropin, given intramuscularly, IBSA Pharmaceutical company, headquartered in Lugano, Switzerland). Oocyte retrieval took place 32-36 hours after the injection.
Endometrial Preparation and Embryo Transfer:
All patients in this study will receive frozen embryo transfer, 2 -3 frozen thawed grade I embryo will be transferred intrauterine guided by ultrasound. Endometrial preparation will be done using hormonal replacement therapy (Ethinyl estrogen 25 µg three times daily will be given on day 2 -3 of the cycle till the endometrial thickness will be > 6-8 mm ( then we will add prontogest 400 mg vaginal suppository twice daily with 40 mg duphastone). Embryo transfer will be done 5 – 7 days after progesterone administration and all this medication will continue for at least three month in case of pregnancy.
Primary Outcome Measures:
1. Clinical pregnancy rate (appearance of intrauterine gestational sac with fetal pole and positive cardiac pulsation by vaginal ultrasound).
2. Premature LH surge (LH on the day of hCG injection).
Secondary Outcome Measures:
1. Number of follicles
2. Number of oocytes retrieved
3. Number of MII oocytes ( Egg quality)
4. Embryos grading
5. Ovarian hyperstimulation syndrome (OHSS)
6. Endometrial thickness
7. Fertilization rate
8. 1st trimester high risk of miscarriage
9. Incidence of multiple pregnancies
10. Cost effectiveness
This study has been shown the following results: There was no stastically significant differences regarding the basic demographic data, regarding age, type of infertility, duration of infertility, and body mass index between both groups. Meanwhile, there was no statistically significant differences in the basal hormonal levels regarding FSH, LH, Prolactin, TSH, and AMH, between both groups (p < 0.05). On the other side, There is statistically significant difference decrease in the endometrial thickness at the time of hCG injection in PPOS group (3.3 ± 1) compared to the endometrial thickness in GnRH - antagonist ( 4.9 ± 1.3) with P value < 0.001*). However, there is statistically signifant differences in the median number of injected mature oocytes MII (p = 0.004*), number of Graafian vesicles (GV, p < 0.001* ), fertilization rate (p = 0.002*), pregnancy rate, (p < 0.05*), there was no statiscically significant differences in multiple pregnancies between both groups (p > 0.05).
This study showed also no occurance of severe form of OHSS in both groups, howevere, there was less incidence of OHSS in PPOS group than GnRH-antagonist group particulary mild and moderate form. Moreover, this study has been shown that there is significantly suppressed LH level at the time of hCG administration preventing premature LH surge in PPOS group (3.2 ± 0.9) in comparison with LH level in GnRH –antagonist group (4.7 ± 1.4) with p < 0.001). In present study, the median grading of the embryos particularly grade I embryos was statistically significant higher in PPOS group (median11.5; range 6 - 16 ) than in GnRH – antagonist group ( median, 4; range, 2 – 8) with
p < 0.001.
Regarding the total Cost Effectiveness, this study showed there was a highly significant reduction in the total patient cost in PPOS (8493 ± 1649) compared to (15500 ± 2898) in GnRH – antagonist group with p < 0.001). In conclusion, PPOS is considered to be effective, acceptable because of easy oral use with higher fertilization, and clinical pregnancy rates, with less OHSS complications particularly the mild and moderate forms. In addition our results showed a positive correlation between E2 level at the time of hCG injection and OHSS in both PPOS group (r = 0.394, P = 0.005) GnRH – antagonist group (r = 0.360, p = 0.01). Howovere, there was no correlation between LH level at the time of hCG injection and pregnancy rate in both PPOS group (r = - 0.200, P = 0.164) GnRH – antagonist group ( r = 0.006, p = 0.969).