Oral Contraceptive Pill Pretreatment in Polycystic Ovary Syndrome Patients Undergoing IVF/ICSI Using the Gonadotrophin Releasing Hormone Antagonist Protocol (A Randomized Controlled Trial)
试验速览
- 阶段
- 1 期
- 入组人数
- 740
- 试验地点
- 1
- 主要终点
- Ongoing pregnancy rate
研究概览
简要总结
373 women with PCOS undergoing a trial of IVF/ICSI will receive OCP from day 2 of the preceding cycle for 21 days followed by GnRH antagonist COH.
Another 373 women with PCOS undergoing a trial of IVF/ICSI will start GnRH antagonist COH directly without OCP pretreatment.
Both groups will be followed up for effect on ongoing pregnancy rate.
详细描述
The study will include 740 women with polycystic ovary syndrome undergoing IVF/ICSI cycle using flexible antagonist protocol.
Randomization:
Patients fulfilling the inclusion criteria will be randomized to two groups.
Study Group:
This group will include 373 women with PCOS undergoing a trial of IVF/ICSI. This group will receive OCP from day 2 of the preceding cycle for 21 days followed by GnRH antagonist COH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 39 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age 18-39 years of age.
- •BMI 18-29 Kg/m2
- •Polycystic ovary syndrome, diagnosed - according to the revised 2003 consensus on diagnostic criteria of polycystic ovary syndrome by the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group - by the presence of two of the following three diagnostic features:
- •Oligo- or anovulation [defined as fewer than eight episodes of menstrual bleeding per year or menses that occur at intervals greater than 35 days].
- •Clinical hyperandrogenism [defined by the presence of hirsutism (assessed by a modified Ferriman-Gallwey score ≥ 8), acne or androgenic alopecia] and/or biochemical signs of hyperandrogenism [defined by elevated free androgen index]
- •Polycystic ovaries [defined as presence of 12 or more follicles in each ovary measuring 2 - 9 mm in diameter, and/or increased ovarian volume > 10 mL) in the early follicular phase (cycle days 3 - 5) in regularly menstruating women. Oligo-/amenorrhoeic women should be scanned either at random or between days 3 and 5 after a progestin-induced withdrawal bleeding. This definition does not apply to women taking oral contraceptive pills, since their use modifies ovarian morphology in normal women and putatively in women with PCO.
- •After exclusion of other etiologies (congenital adrenal hyperplasia, androgen secreting tumors, Cushing's syndrome, hypothyroidism and hyperprolactinemia).
- •Normal transvaginal ultrasonography apart from polycystic ovaries (see before).
- •Normal office hysteroscopy.
- •Normal hysterosalpingography.
- •Absence of any structural pathological findings in laparoscopy apart from enlarged sclerotic polycystic ovaries.
- •Normal hormonal profile (apart from hormonal abnormalities associated with PCOS), e.g. normal thyroid function tests
- •Normal parameters of male semen analysis according to WHO criteria
- •First trial IVF/ICSI.
- •Written and signed informed consent by the patient to participate in the study.
排除标准
- •Age more than 39 years.
- •BMI more than 29 Kg/m2
- •Abnormal ultrasonographic finding, e.g. endometrial polyps, fibroids or ovarian cysts.
- •Abnormal hysteroscopic finding, e.g. endometrial polyps, endometrial hyperplasia or fibroid.
- •Abnormal hysterosalpingographic finding, e.g. hydrosalpinx or peritoneal adhesions.
- •Abnormal male or female karyotyping.
- •Abnormal endocrinological profile during ovarian stimulation not attributed to PCOS, e.g. hypothyroidism, FSH > 12 mIU/mL on day
- •Previous trials of IVF/ICSI.
- •Positive anticardiolipin antibodies or lupus anticoagulant.
- •Positive thrombophilia screen.
- •Abnormal semen analysis parameters according to WHO criteria
- •Any hormonal treatment within the last 3 months.
- •Any treatment for insulin resistance within the last 3 months, e.g. metformin or leptin.
- •Any chronic medical disorder, e.g. hypertension, autoimmune disorders, ... etc.
- •Any category 4 medical condition that contraindicates the usage of OCP according to the WHO Medical eligibility criteria, 2015:
- •Smoking with age ≥ 35 years and cigarettes ≥ 15 /day.
- •Hypertension (systolic ≥ 160 mmHg or diastolic ≥ 90 mmHg).
- •Hypertension with vascular disease.
- •Previous history or acute DVT/PE.
- •Any known thrombogenic mutations.
- •Complicated valvular heart disease.
- •Systemic lupus erythematosus with positive or unkown antiphospholipid antibodies.
- •Migraine with aura.
- •Diabetes with nephropathy/neuropathy/retinopathy.
- •Diabetes > 20 years.
- •Acute hepatitis, severe cirrhosis or liver tumors.
- •Mental condition rendering the patients unable to understand the nature, scope and possible consequences of the study.
研究组 & 干预措施
OCP Group
This group will include 373 women with PCOS undergoing a trial of IVF/ICSI. This group will receive 0.075mg gestodene/0.03mg ethinylestradiol (Gynera®, Bayer Schering Pharma AG, Germany) from day 2 of the preceding cycle for 21 days followed by GnRH antagonist COH.
干预措施: 0.075mg gestodene/0.03mg ethinylestradiol (Drug)
结局指标
主要结局
Ongoing pregnancy rate
时间窗: 20 gestational weeks
Number of pregnancies completing ≥20 weeks gestational age expressed per 100 embryo transfer cycles
次要结局
- Chemical pregnancy rate(6 gestational weeks)
- Clinical pregnancy rate(6 gestational weeks)
- Live birth rate(38 gestational weeks)
研究者
Khaled Afifi
Assistant lecturer of O&G
Ain Shams University