Comparison Between Oral Estradiol 8 mg Versus 12 mg for Endometrial Preparation in Programmed Frozen Embryo Transfer Cycles on Clinical Pregnancy Rate: A Double-Blind Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 850
- 试验地点
- 2
- 主要终点
- clinical pregnancy rate
研究概览
简要总结
The goal of this clinical trial is to learn whether 12 mg or 8 mg of oral estradiol valerate is better for preparing the endometrium in women undergoing hormone replacement frozen embryo transfer (HRT-FET) cycles. It also aims to assess how these two doses affect pregnancy outcomes and cycle success.
The main questions it aims to answer are:
Does oral estradiol 12 mg/day improve the clinical pregnancy rate compared with 8 mg/day? Do the two doses differ in endometrial thickness, cycle cancellation, miscarriage, and embryo transfer outcomes?
Researchers will compare oral estradiol valerate 12 mg/day with oral estradiol valerate 8 mg/day to see whether the higher dose leads to better endometrial preparation and higher clinical pregnancy rates.
Participants will:
Be randomly assigned to receive either oral estradiol 8 mg/day or 12 mg/day Undergo endometrial preparation before frozen embryo transfer Have endometrial thickness assessed before starting progesterone Undergo embryo transfer and follow-up to assess clinical pregnancy and other outcomes
详细描述
Study Methods 7.1 Study population Women undergoing assisted reproductive technology and scheduled for their first autologous programmed HRT-FET cycle will be screened for eligibility. Randomization will occur at the start of the FET cycle; ovarian stimulation, oocyte retrieval, fertilization, embryo culture, and vitrification from the antecedent IVF/ICSI cycle will have occurred before trial entry and will not constitute part of the randomized intervention.
7.2 Inclusion criteria
- Women aged 18-40 years.
- Body mass index <30 kg/m².
- First autologous programmed HRT-FET cycle.
- Endometrial preparation planned using oral estradiol valerate only.
- Vitrified embryos derived from a previous autologous IVF or ICSI cycle.
- Planned transfer of vitrified-warmed day-5 blastocyst(s).
- Normal uterine cavity documented within the preceding 12 months.
- Baseline transvaginal ultrasonography on cycle day 2 or 3 showing no ovarian cyst, dominant follicle, or intracavitary pathology.
- Ability and willingness to provide written informed consent.
- Ovulatory-factor infertility, including polycystic ovary syndrome, will be eligible provided all other criteria are fulfilled.
7.3 Exclusion criteria
- Contraindication to estrogen treatment, including current or previous breast cancer or endometrial cancer, deep venous thrombosis, pulmonary embolism, stroke, or allergy to the study medication.
- Irregular unexplained vaginal bleeding.
- Untreated thyroid disorder or hyperprolactinemia.
- Uncontrolled diabetes mellitus or hypertension.
- Significant renal, hepatic, or severe systemic disease.
- Uterine abnormality, untreated hydrosalpinx, or untreated intracavitary uterine pathology detected by ultrasonography or hysteroscopy.
- Donor-oocyte, donor-embryo, gestational-carrier, or PGT-A cycle.
- Natural or modified-natural FET cycle; transdermal, vaginal, or mixed-estrogen regimen; or use of letrozole, gonadotropins, or GnRH agonists for endometrial preparation.
- Premature ovarian insufficiency.
- Stage III-IV endometriosis.
- Recurrent implantation failure or recurrent miscarriage.
- Abnormal parental karyotype.
- Active smoking.
- Anticipated or documented difficult embryo transfer.
- Refusal or withdrawal of consent. 7.4 Baseline assessment Before treatment initiation, all eligible participants will undergo standardized personal, menstrual, obstetric, infertility, medical, surgical, and family history taking, followed by general and gynecological examination. Routine investigations will be obtained according to unit practice. Serum thyroid-stimulating hormone and prolactin will be assessed to exclude relevant endocrine disorders. Baseline transvaginal ultrasonography will be performed on cycle day 2 or 3 to document endometrial thickness and exclude ovarian cysts, a dominant follicle, or uterine-cavity pathology.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, treating physicians, sonographers, embryologists, outcome assessors, and statisticians remained blinded to group assignment throughout the study. Participants were randomized in a 1:1 ratio to oral estradiol valerate 8 or 12 mg/day. Randomization was stratified by study center using separate computer-generated permuted-block sequences prepared by an independent statistician who had no role in participant enrollment, treatment, outcome assessment, or data analysis. Allocation was concealed using sequentially numbered, opaque, sealed envelopes prepared and retained by personnel independent of recruitment and clinical care. After eligibility confirmation and informed consent, the study coordinator opened the next envelope and dispensed the corresponding sequentially numbered medication pack. Participants, treating physicians, sonographers, embryologists, outcome assessors, and statisticians remained unaware of treatment allocation. No emergency unblinding occurred. Serum est
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria
- •Women aged 18-40 years.
- •Body mass index <30 kg/m².
- •First autologous programmed HRT-FET cycle.
- •Endometrial preparation planned using oral estradiol valerate only.
- •Vitrified embryos derived from a previous autologous IVF or ICSI cycle.
- •Planned transfer of vitrified-warmed day-5 blastocyst(s).
- •Normal uterine cavity documented within the preceding 12 months.
- •Baseline transvaginal ultrasonography on cycle day 2 or 3 showing no ovarian cyst, dominant follicle, or intracavitary pathology.
- •Ability and willingness to provide written informed consent.
- •Ovulatory-factor infertility, including polycystic ovary syndrome, will be eligible provided all other criteria are fulfilled.
排除标准
- •Contraindication to estrogen treatment
- •History of breast cancer or endometrial cancer
- •History of deep venous thrombosis, pulmonary embolism, or stroke
- •Allergy to the study medication
- •Irregular vaginal bleeding
- •Thyroid disorder
- •Hyperprolactinemia
- •Uncontrolled diabetes mellitus
- •Uncontrolled hypertension
- •Significant liver disease
- •Significant kidney disease
- •Severe systemic illness
- •Uterine abnormality
- •Untreated hydrosalpinx
- •Untreated pathology inside the uterine cavity
- •Donor-oocyte cycle
- •Donor-embryo cycle
- •Gestational-carrier cycle
- •Preimplantation genetic testing for aneuploidy (PGT-A) cycle
- •Natural cycle or modified natural cycle for endometrial preparation
- •Use of transdermal, vaginal, or mixed estrogen regimens
- •Use of letrozole, gonadotropins, or GnRH agonists for endometrial preparation
- •Premature ovarian insufficiency
- •Stage III or IV endometriosis
- •Recurrent implantation failure
- •Recurrent miscarriage
- •Abnormal parental karyotype
- •Active smoking
- •Difficult embryo transfer
- •Refusal to participate
研究组 & 干预措施
Group A: received 8 mg daily oral estradiol valerate daily.
Women in the 8 mg group received four active 2 mg estradiol valerate tablets plus two matched placebo tablets.
干预措施: Progynova® (Drug)
Group B: received 12 mg daily oral estradiol valerate daily.
women in the 12 mg group received six active 2 mg estradiol valerate tablets
干预措施: Progynova® (Drug)
结局指标
主要结局
clinical pregnancy rate
时间窗: 6 to 8 weeks after embryo transfer
Clinical pregnancy rate is defined as the proportion of participants with one or more gestational sacs detected by transvaginal ultrasound after frozen embryo transfer.
次要结局
- Cycle cancellation rate(From treatment initiation until cycle cancellation before embryo transfer or embryo transfer if the cycle continued, assessed up to 8 weeks per treatment cycle.)
- Live birth rate(At delivery after 24 completed weeks of gestation)
- Endometrial thickness on the day of progesterone initiation(On the day of progesterone initiation, approximately cycle day 10-18)
- Serum estradiol concentration on the day of progesterone initiation(On the day of progesterone initiation, approximately cycle day 10-18)
- Biochemical pregnancy rate(14 days after embryo transfer)
- Implantation rate(Approximately 5-7 weeks of gestation)
- Ongoing pregnancy rate(At ≥12 completed weeks of gestation)
- Miscarriage rate(From confirmation of clinical pregnancy through <24 completed weeks of gestation)
- Multiple pregnancy rate(At first pregnancy ultrasonography, approximately 5-7 weeks of gestation)
- Birth plurality(At delivery, up to approximately 42 weeks of gestation)
- Treatment-related symptoms(From initiation of estradiol treatment until embryo transfer or cycle cancellation, approximately 2-4 weeks)
研究者
ahmed nagy shaker ramadan
lecturer of obstetrics and gynecology
Cairo University