Frozen Embryo Transfer in Natural and Hormonal Replacement Cycles

Comparison of Pregnancy Outcomes in Frozen Embryo Transfer in Natural and Hormonal Replacement Cycles: a Randomized Controlled Trial

This study is a prospective randomized controlled trial to compare the pregnancy outcomes of frozen embryo transfer in natural and hormonal replacement cycles. The study population consisted of all infertile women with regular menstrual cycles who will undergo IVF/ICSI and frozen embryo transfer in Reproductive Biomedicine Research Center, Royan institute, Tehran Iran.

In this study all patients who will undergo frozen embryo transfer are randomly allocated to be prepared for transfer by using either natural cycle (with or without hCG for ovulation induction) or Hormonal cycle (with or without administration of GnRH-a) In natural cycle without hCG, daily monitoring of urinary LH is started from day eight of the cycle and frozen-thawed embryo transfer is planned 3-5 days after detection of LH surge, observing mature follicles in ultrasound and endometrial thickness over 7mm for cleavage embryos. In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed 3-5 days later in cleavage stage. In group 3, injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7 days if endometrial thickness is adequate, Estradiol administration will be continued with the same dose and 100mg Progesterone is administered before embryo transfer, otherwise patients are candidates for higher dosage of Estradiol till favourable endometrial thickness is achieved. In the hormonal group without GnRH-a, endometrial preparation will be started with daily administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for 6 days. Then treatment will be continued similar to the 3rd group.

In natural cycle without hCG, daily monitoring of urinary LH is started from day eight of the cycle and frozen-thawed embryo transfer is planned 3-5 days after detection of LH surge, observing mature follicles in ultrasound and endometrial thickness over 7mm for cleavage embryos.

In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed 3-5 days later in cleavage stage.

In this group , injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7 days if endometrial thickness is adequate, Estradiol administration will be continued with the same dose and 100mg Progesterone is administered before embryo transfer, otherwise patients are candidates for higher dosage of Estradiol till favourable endometrial thickness is achieved.

In the hormonal group without GnRH-a, endometrial preparation will be started with daily administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for 6 days. Then treatment will be continued similar to the 3rd group.

In this study all patients who will undergo frozen embryo transfer are randomly allocated to be prepared for transfer by using either natural cycle (with or without hCG for ovulation induction) or Hormonal cycle (with or without administration of GnRH-a).

In natural cycle with hCG, after detection of mature follicles in ultrasound and endometrial thickness over 7mm, 10,000IU hCG is injected for ovulation and embryo transfer is performed 3-5 days later in cleavage stage.

In group 3, injection of GnRH agonist (Superfact) at a subcutaneous daily dose of 0.5 mg is started on the day 17-19 of the natural menstrual cycle. Once pituitary desensitization is confirmed, hormonal treatment is commenced with 4mg/day oral Estradiol valerate and after 7 days if endometrial thickness is adequate, Estradiol administration will be continued with the same dose and 100mg Progesterone is administered before embryo transfer, otherwise patients are candidates for higher dosage of Estradiol till favourable endometrial thickness is achieved.

In the hormonal group without GnRH-a, endometrial preparation will be started with daily administration of 6 mg Estradiol valerate from the 2nd day of the natural menstrual cycle for 6 days. Then treatment will be continued similar to the 3rd group.

Inclusion Criteria: Patients with regular mensturation cycles Age 20-37 years Patients who underwent long protocol Body mass index (BMI) ≤ 30 kg/m2 Patients who will undergo frozen embryo transfer for the first time Exclusion Criteria: Oocyte or embryo donation cycles Uterine diseases or malformations Hyper prolactinemia Thyroid disorders Tuberculosis Recurrent abortion history Severe endometriosis Ovulation disorders

Department of Endocrinology and Female Infertility at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Department of Endocrinology and Female Infertility at Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Madani T, Ramezanali F, Yahyaei A, Hasani F, Bagheri Lankarani N, Mohammadi Yeganeh L. Live birth rates after different endometrial preparation methods in frozen cleavage-stage embryo transfer cycles: a randomized controlled trial. Arch Gynecol Obstet. 2019 Apr;299(4):1185-1191. doi: 10.1007/s00404-019-05062-7. Epub 2019 Feb 1.