Modified Downregulation for Women With Adenomyosis of the Uterus Prior to Frozen-thawed Embryo Transfer.
试验速览
- 阶段
- 4 期
- 入组人数
- 162
- 试验地点
- 1
- 主要终点
- Clinical pregnancy rate
研究概览
简要总结
1 in 7 couples experience difficulty in conceiving. Many will require in vitro fertilization (IVF). IVF involves an initial period of downregulation to suppress the ovaries and prevent premature ovulation. Hormone injections are then used to stimulate a woman's ovaries to produce eggs which are removed by a minor operation. The harvested eggs are mixed with sperm to create embryos in the laboratory. These embryos are replaced in the womb a few days after they are created (fresh embryo transfer). Any remaining embryos are frozen such that they can be thawed and transferred at a later date (frozen thawed embryo transfer, FTET).
The investigators have previously shown that the presence of moderate or severe adenomyosis significantly reduces the chance of clinical pregnancy after embryo transfer. The purpose of this study is to examine whether it is possible to improve the chance of clinical pregnancy in these women by modifying the IVF protocol they undergo for FTET.
The hypothesis is that a prolonged downregulation regimen for women with adenomyosis would reduce the inflammatory reaction in the endometrium of these women and thus improve the chance of implantation after embryo transfer.
Consenting patients will be offered FTET. Those proceeding will be randomized to one of two protocols (A - standard protocol vs. B - prolonged downregulation protocol). Women will also be offered a questionnaire before and after IVF treatment to assess their adenomyosis symptoms .
The primary outcome of the study is clinical pregnancy defined as an intrauterine pregnancy with a visible heart beat older than 6 weeks gestation. Secondary outcomes include livebirth, pregnancy loss (biochemical pregnancy, miscarriage, ectopic pregnancy, stillbirth, termination of pregnancy), gestational age at delivery, birth weight, neonatal mortality, major congenital anomaly, serious medication reaction, number of frozen embryos available for transfer, number of days to achieve optimal endometrial thickness.
详细描述
Objectives:
The primary objective is to determine whether modified downregulation before embryo transfer improves the chance of clinical pregnancy after embryo transfer in women with moderate/severe adenomyosis of the uterus. A secondary objective is to evaluate the impact of IVF on adenomyosis-related symptom presence, severity and progression.
Type of trial:
A randomised, controlled, multi-site trial in women with moderate/severe adenomyosis of the uterus undergoing frozen-thawed embryo transfer.
Trial design and methods:
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
盲法说明
It will not be possible to perform blinding due to the difference in frequency of administration of medication between the two protocols, therefore an open label method will be used.
入排标准
- 年龄范围
- 18 Years 至 42 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Couples who are undergoing a cycle of IVF/ICSI, where a cycle is defined as egg collection following ovarian stimulation.
- •The female partner is ≥18 and < 42 years of age.
- •The female partner has a BMI <
- •Two out of three of the following criteria are met: AMH >5.4, FSH <8.9, antral follicle count >
- •Moderate or severe adenomyosis of the uterus diagnosed on ultrasound scan.
- •Both partners are willing and able to provide written informed consent.
排除标准
- •Concurrent and/or recent involvement in other research that is likely to interfere with the intervention within the previous 3 months of study enrolment.
- •Previous open or laparoscopic myomectomy
- •Uterine fibroids (untreated FIGO Type 0-I-II and type III-IV fibroids > 3 cm)
- •Use of GnRH analogues within previous 3 months.
- •Severe male factor infertility (sperm count < 2 x 106/ml, use of surgically retrieved spermatozoa)
- •Couples who in the opinion of the researcher by virtue of language or learning impairment would be unable to give fully informed consent to the study.
研究组 & 干预措施
Standard downregulation with GnRH analogue
Participants in this arm will be assigned to the routine IVF protocol currently being used in the investigators' IVF unit, as outlined below, with one week of downregulation. Downregulation is the suppression of the ovaries during an IVF cycle in order to perform controlled ovarian stimulation and prevent premature ovulation.
Start progesterone (Norethisterone 5mg twice daily orally) on day 14 of downregulation cycle and continue for 11 days. Start GnRH analogue (Buserelin 0.5ml subcutaneously once daily) on day 21 of downregulation cycle and reduce to 0.2ml on day 1 of bleed. Baseline scan on day 1 - 5 of bleed and start oestrogen (Progynova 2mg three times daily orally). Serial scanning from day 10 until endometrial thickness more than 8mm. Once endometrial thickness more than 8mm start progesterone (Cyclogest 400mg twice daily vaginally/rectally and Lubion 25mg twice daily subcutaneously) and proceed to embryo transfer on appropriate day for embryo age.
干预措施: GnRH analogue downregulation (Drug)
Standard downregulation with GnRH analogue
Participants in this arm will be assigned to the routine IVF protocol currently being used in the investigators' IVF unit, as outlined below, with one week of downregulation. Downregulation is the suppression of the ovaries during an IVF cycle in order to perform controlled ovarian stimulation and prevent premature ovulation.
Start progesterone (Norethisterone 5mg twice daily orally) on day 14 of downregulation cycle and continue for 11 days. Start GnRH analogue (Buserelin 0.5ml subcutaneously once daily) on day 21 of downregulation cycle and reduce to 0.2ml on day 1 of bleed. Baseline scan on day 1 - 5 of bleed and start oestrogen (Progynova 2mg three times daily orally). Serial scanning from day 10 until endometrial thickness more than 8mm. Once endometrial thickness more than 8mm start progesterone (Cyclogest 400mg twice daily vaginally/rectally and Lubion 25mg twice daily subcutaneously) and proceed to embryo transfer on appropriate day for embryo age.
干预措施: Participant questionnaire (Other)
Prolonged downregulation with GnRH analogue
Participants in this arm will be exposed to an additional five weeks of downregulation using a GnRH analogue. Downregulation is the suppression of the ovaries during an IVF cycle in order to perform controlled ovarian stimulation and prevent premature ovulation.
Baseline scan on day 1-5 of bleed and administer GnRH analogue (Leuprorelin acetate 3.75 mg subcutaneously single injection). 28 days later administer second dose of GnRH analogue (Leuprorelin acetate 1.875 mg subcutaneously), and 21 days later start oestrogen (Progynova 2 mg three times daily orally). Serial scanning from day 10 of oestrogen until endometrial thickness more than 8mm. Once endometrial thickness more than 8mm start progesterone (Cyclogest 400mg twice daily vaginally/rectally and Lubion 25mg twice daily subcutaneously) and proceed to embryo transfer on appropriate day for embryo age.
干预措施: GnRH analogue downregulation (Drug)
Prolonged downregulation with GnRH analogue
Participants in this arm will be exposed to an additional five weeks of downregulation using a GnRH analogue. Downregulation is the suppression of the ovaries during an IVF cycle in order to perform controlled ovarian stimulation and prevent premature ovulation.
Baseline scan on day 1-5 of bleed and administer GnRH analogue (Leuprorelin acetate 3.75 mg subcutaneously single injection). 28 days later administer second dose of GnRH analogue (Leuprorelin acetate 1.875 mg subcutaneously), and 21 days later start oestrogen (Progynova 2 mg three times daily orally). Serial scanning from day 10 of oestrogen until endometrial thickness more than 8mm. Once endometrial thickness more than 8mm start progesterone (Cyclogest 400mg twice daily vaginally/rectally and Lubion 25mg twice daily subcutaneously) and proceed to embryo transfer on appropriate day for embryo age.
干预措施: Participant questionnaire (Other)
结局指标
主要结局
Clinical pregnancy rate
时间窗: 6 weeks after embryo transfer
Clinical pregnancy is defined as an intrauterine pregnancy with a visible heart beat older than 6 weeks gestation.
次要结局
- Major cogenital anomaly(9 months after embryos transfer)
- Serious medication reaction(9 months after embryo transfer)
- Number of days to achieve optimal endometrial thickness(Start of endometrial preparation until day of embryo transfer)
- Neonatal mortality(9 months after embryo transfer)
- Pregnancy loss(9 months after embryo transfer)
- Gestational age at delivery(9 months after embryo transfer)
- Birthweight at delivery(9 months after embryo transfer)
- Presence and severity of adenmyosis-related symptoms(2 months after embryo transfer)
- Number of frozen embryos available for transfer(Day of embryo transfer)
- Livebirth(9 months after embryo transfer)