Double Ovarian Stimulation in Cases of Preimplantation Genetic Testing: Comparison of Embryo Quantity and Embryonic Quality Using MitoScore
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 136
- 试验地点
- 1
- 主要终点
- Rate of euploid embryos per cycle
研究概览
简要总结
Since preimplantation genetic testing (PGT) is being more frequently requested from patients as women pursue infertility treatments at an advanced age with a poorer prognosis, sometimes physicians are compelled to perform several stimulation cycles to obtain more eggs and, consequently, a greater number of biopsied embryos. Hence, the idea of carrying out this study arises as an attempt to optimize each menstrual cycle to the maximum.
It is believed that the double stimulation (DuoStim) protocol could be an alternative for this group of patients, allowing to obtain a larger number of oocytes in a shorter period, thus, increasing the number of biopsied embryos and possibly decreasing the interval to achieve a successful pregnancy.
The investigators aim to evaluate the potential usefulness of the DuoStim protocol for patients desiring to obtain oocytes as soon as possible. Using PGT, the investigators will compare the rate of euploid embryos per cycle in patients undergoing DuoStim protocol versus patients undergoing two conventional controlled ovarian hyperstimulation in consecutive cycles. Patients will include women with advanced age and poor response.
This is a unicentric, prospective, randomized, non-blind, parallel-group controlled phase IV clinical study. The investigators hypothesize that the rate of euploid embryos per cycle is similar in the DuoStim group compared to the group undergoing two conventional controlled ovarian hyperstimulation in consecutive cycles.
Furthermore the investigators will evaluate if there are differences regarding the number of total oocytes obtained, the number of mature oocytes, the number of biopsied blastocysts and the MitoScore index of the available euploid embryos.
详细描述
Classically, the follicular development was thought to occur only during the follicular phase of the menstrual cycle. However, new data demonstrated several waves of cyclic development of the antral follicles within the same menstrual cycle. Some authors insist that follicles formed during the luteal phase may have a similar ovulation potential of those formed in the follicular phase, thus offering new possibilities for ovarian stimulation.
Due to the use of vitrification technique and the appearance of the gonadotropins, physicians have been allowed to innovate the protocols applied to controlled ovarian hyperstimulation and have been able to obtain more oocytes in a shorter period for patients requiring rapid intervention, such as oncologic patients. Because of the accumulated experience with these new approaches, some investigators have recently proposed a double stimulation (DuoStim) protocol. Evidence of the competence of oocytes obtained from the luteal phase have been recently defined and published. Also, it has not been related with an increased risk for congenital anomalies.
The DuoStim is a protocol consisting of two stimulations within the same menstrual cycle, one in the follicular phase starting in day 2 of the cycle and the other in the luteal phase starting 5 days after the first ovarian puncture. Trigger is always performed with GnRH agonist.
Additionally, patients demanding infertility treatments are increasingly older and the use of preimplantation genetic testing (PGT) allows for a finer embryo selection along with better reproductive outcomes. Currently, most of PGTs are carried out at the blastocysts stage, which improve the prognosis but, on the contrary, also oblige to frozen those embryos and perform a deferred transfer, lengthening the procedure.
Another innovative tool for a more accurate embryo selection which has been recently described is the MitoScore. The MitoScore is a mitochondrial biomarker index developed by Igenomix aiming to indicate the energetic status of the embryo. It intends to select those embryos with best implantation potential and, therefore, more likely to result in an ongoing pregnancy after an IVF treatment. It is calculated dividing the number of mitochondrial DNA copies by the amount of nuclear DNA. Although still controversial, it has been proved by some authors to increase success rates of implantation and ongoing pregnancies in IVF cycles and to diminish the number of multiple gestations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 35 Years 至 42 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent;
- •35-42 years of age;
- •Patients from the IVI Madrid undergoing controlled ovarian hyperstimulation cycle including PGT analysis for infertility treatment;
- •BMI 18-30 kg/m2;
- •Suspicion of suboptimal or poor response:
- •AMH < 1.5 ng/mL; AFC < 8; FSH > 10; Poor response in a previous cycle (defined as < 6 oocytes).
排除标准
- •Simultaneous participation in another clinical trial or in any other study that could result in a confounding factor.
研究组 & 干预措施
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: human menopausal gonadotropin (Drug)
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: GnRH antagonist (Drug)
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: GnRH analog (Drug)
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Trophectoderm biopsy (Procedure)
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: MitoScore (Diagnostic Test)
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Intracytoplasmic sperm injection (Procedure)
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Ovarian puncture (Procedure)
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Preimplantation genetic test (Diagnostic Test)
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Embryo transfer (Procedure)
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Pregnancy test (Diagnostic Test)
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Embryo freezing (Procedure)
DuoStim
Two controlled ovarian stimulation within the same menstrual cycle using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Embryo thawing (Procedure)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: human menopausal gonadotropin (Drug)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: GnRH antagonist (Drug)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: GnRH analog (Drug)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Trophectoderm biopsy (Procedure)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: MitoScore (Diagnostic Test)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Intracytoplasmic sperm injection (Procedure)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Ovarian puncture (Procedure)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Preimplantation genetic test (Diagnostic Test)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Embryo transfer (Procedure)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Pregnancy test (Diagnostic Test)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Embryo freezing (Procedure)
Conventional Stimulation
Two controlled ovarian stimulation in different menstrual cycles using human menopausal gonadotropin 225 IU/day subcutaneously, GnRH antagonist in a dose of 0.25 mg/day subcutaneously and 0.2 mg of GnRH analog to induce oocyte maturation. It will be followed by ovarian puncture, oocyte isolation, intracytoplasmic sperm injection and trophectoderm biopsy at the blastocyst stage. Preimplantation genetic test and MitoScore will be performed in all the embryos prior to the embryo transfer. At this step embryos will be frozen to wait for the results. Chromossomally normal embryos will be thawed and transferred to the uterus in a deferred cycle. A pregnancy test will be performed when appropriate.
干预措施: Embryo thawing (Procedure)
结局指标
主要结局
Rate of euploid embryos per cycle
时间窗: up to 9 months
Rate of chromosomally normal embryos per cycle in the DuoStim group compared to the group undergoing two controlled ovarian hyperstimulation in consecutives cycles.
次要结局
- Number of fertilized oocytes(up to 9 months)
- Number of biopsied blastocysts(up to 9 months)
- MitoScore index of the euploid embryos(up to 9 months)
- Implantation rate(up to 9 months)
- Pregnancy rate(up to 9 months)
- Number of oocytes obtained(up to 9 months)
- Abortion rate(up to 9 months)
- Time until embryo transfer(up to 9 months)