* Adenomyosis is a benign gynecological disease in which the endometrial stroma invades the uterine myometrium. Adenomyosis affects approximately 10% of women of reproductive age. There are several hypothetical mechanisms in adenomyosis-associated infertility, including dysregulations of the myometrial architecture and function, chronic inflammation, presence of local oxygen, and altered endometrial function, which can cause implantation failure. The abnormal presence of endometrial tissue composed of glands and stroma impacts uterine smooth muscle's regular contractile function and peristalsis, resulting in menometrorrhagia, infertility, and adverse obstetric consequences. There is currently no consensus on the optimal protocol for endometrial preparation in this population, and a lack of data on this issue. Current protocols include routine protocols with or without the pre-treatment of GnRH agonist. However, it is still controversial whether GnRH agonist down-regulation can help patients with adenomyosis have better reproductive outcomes. To our knowledge, there have not been any randomized controlled trials to investigate the effectiveness of the protocols used for endometrial preparation in women with adenomyosis undergoing frozen embryo transfer.
* This will be a superiority-designed randomized clinical trial.
* This trial will be conducted at My Duc Hospital, Ho Chi Minh City, Vietnam. Potentially eligible women will be provided information about the trial as long as their stimulation cycles are initiated.
* Screening for eligibility will be performed by treating physicians on days 2nd - 4th of the menstrual cycle in the subsequent frozen embryo transfer cycles. Patients will be provided a copy of the informed consent documents. Written informed consent will be obtained from all women by the investigator before enrollment.
* Women will be randomized (1:1) to either AC (artificial cycle) or GnRHa+AI - AC (Down-Regulation with GnRH agonist and Letrozole combined with artificial cycle) protocols using block randomization with a variable block size of 4, 6, using HOPE Epi with a computer-generated random list.
* Artificial cycle (AC): the endometrium will be prepared using oral estradiol valerate (Valiera; Abbott) 6 mg/day starting from the second or fourth day of the menstrual cycle (5). The endometrial thickness will be monitored from the tenth day of estradiol-priming onwards, and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day will be initiated when endometrial thickness reaches 7 mm or more and received oestradiol valerate for at least nine days.
Embryo transfer will be scheduled by the time of the initiation of progesterone and embryo stages. Hormonal support will consist of oral estradiol valerate 4 mg/day and vaginal progesterone (Cyclogest®; Actavis) 400 mg twice times a day until the 7th week of gestation. Subsequently, progesterone alone (Cyclogest®; Actavis) at 400 mg twice times a day will be continued for luteal phase support until the 12th week of gestation.
\- GnRH agonist + Letrozole - Artificial cycle protocol (GnRHa+AI - AC):
* Pre-treatment with GnRH agonist: GnRHa (Triptorelin - Diphereline®, Ipsen, France) will be injected at a dose of 3.75 mg on days 2nd - 4th of menstruation. In addition to GnRHa administration duration, the patients will be indicated letrozole 2.5 mg daily (Femara®, Novartis, Switzerland) to prevent the estradiol flare-up effect from the day of GnRH agonist injection. Repeat the same regimen for the second time 28 days after the first injection of GnRH agonist.
* After 55 days of Down Regulation with GnRH agonist, before starting the artificial cycle protocol for endometrial preparation, estradiol serum level will be tested before endometrial preparation.
* Endometrial preparation with AC protocol will be started 28 days after the second injection of GnRH agonist, as described previously
Frozen embryo transfer:
A maximum of 2 cleavage-stage embryos or 1 blastocyst will be thawed on the day of embryo transfer, three or five days after the start of progesterone. Two hours after thawing, surviving embryos will be transferred into the uterus under ultrasound guidance using a soft uterine catheter (Gynétics®, Belgium).
\- Future babies' health evaluation and cost-effectiveness analysis will also be performed separately.
