Frozen embryo transfer (FET) is increasingly adopted strategy in modern IVF. Among the many factors that have contributed to such change, the pursuit of an ovarian hyperstimulation syndrome free clinic has been strongly required. Improvements in the vitrification and warming processes and the excellent cryo-survival rates have turned FET in our main tool for preventing this complication. Moreover, a freeze all strategy has proven to provide excellent or even better pregnancy rates (PRs), not only in high but also in normal responders.

While ART have rapidly evolved in the areas of embryo culture, vitrification and understanding of the embryo development, little progress has been achieved regarding endometrial preparation for FET. Undoubtedly, correct implantation requires a good quality embryo and a suitable decidualized endometrium. Artificial cycles require hormone replacement treatment (HRT) with estradiol and progesterone (P4). However, there is not a single standardized treatment described for optimal endometrial preparation and no protocol has proven superiority in terms of reproductive outcomes.(5, 6) Although artificial preparation is the most convenient method to schedule FET cycles, recent reports have highlighted a potentially detrimental effect of low P4 levels prior to FET on miscarriage and live birth rates (LBRs). These results have been observed both in homologous and oocyte recipient FET cycles(7, 8), but also in FET cycles of embryos that had undergone PGT for aneuploidies (PGT-A).(9) Additional P4 supplementation may be a way to improve reproductive outcomes in these patients.

Our open labelled randomized control study aims to investigate whether patients with low serum P4 levels the day before FET under standard HRT can benefit in terms of clinical and ongoing pregnancy and implantation rates from an individualized luteal phase support consisting in the addition of oral dydrogesterone supplementation or daily subcutaneous P4 injection.

A randomized control trial which will be conducted at El-Shatby University Maternity Hospital and private two private ART centres in Alexandria, Egypt.

120 patients in which HRT-FET cycles with low serum progesterone levels will divided into two groups :

• Group A: 60 patients will be given oral 10 mg dydrogesterone (Duphaston®, Abbott) twice daily or,
• Group B: 60 patients will be given subcutaneous injection 25mg daily (Prolutex®, IBSA).

METHODS Investigation Basal hormonal profile before initiation of treatment, a basal hormonal profile will be performed in all patients (basal FSH, LH, and estradiol levels) Pelvic ultrasound using a transvaginal probe, to assess ovaries, tubes and document uterine size, shape and endometrial thickness.

Endometrial preparation:

A transvaginal scan will be performed on the second day of the menstrual cycle to document baseline endometrial thickness.

HRT preparation of endometrium will be started day two of the cycle by administration of estradiol valerate at dose 8 mg daily.

The endometrial thickness and pattern will be assessed starting from day 10 of estradiol supplementation. If the endometrial thickness is less than 7 mm, oestradiol valerate administration will be continued and reassessed every 3 days up to 21days and if no improvement the cycle will be cancelled.

When the endometrial thickness reaches a minimum of 7 mm with a triple-line appearance, patients will start progesterone supplementation. Vaginal progesterone at a daily dose of 800 mg will administered (cyclogest suppository 400mg. twice daily). Blastocyst transfer will be done after 5 complete days of progesterone administration.

A morning serum progesterone level will be measured 24 hours before embryo transfer. If the serum progesterone level is bellow <10 ng/mL (1) rescue progesterone dose will be started before blastocyst transfer.

Patients with low serum progesterone will be randomized to receive extra progesterone supplementation in the form of either:

• Group A: oral 10 mg dydrogesterone (Duphaston®, Abbott) twice daily or,
• Group B: subcutaneous injection 25mg daily (Prolutex®, IBSA). The serum progesterone will be measured again on the day of embryo transfer and the day after.

The HRT will be continued until a pregnancy test is performed, and in cases of a positive pregnancy test, estradiol valerate and progesterone will be continued till week 10 of gestation.

III. Measuring the level of beta HCG:

The level of HCG will be measured for diagnosis of pregnancy 14 days after embryo transfer.

IV. Detection of Clinical pregnancy rate:

Transvaginal ultrasonography will be used to detect the appearance of the gestational sac with a fetal pole in the uterus two weeks after positive pregnancy test.

Cases will be followed up till the end of first trimester to detect abortion rate.

Inclusion Criteria:

1. Patient prepared for frozen blastocyst transfer.
2. Maternal age ranges from less than 40 years.
3. BMI < 35kg/m2.
4. Normal uterine cavity.

Exclusion Criteria:

1. Uncorrected endometrial, uterine or pelvic pathology.
2. Recurrent implantation failure cases.
3. Patients suffering from recurrent miscarriages.
4. Male factor infertility due to azoospermia