Patients' Preference for Subcutaneous or Vaginal Progesterone as Luteal Support in IVF/ICSI Cycles

Each participant will receive both treatments. During the first IVF/ICSI cycle, the luteal phase will be supplemented with subcutaneous progesterone (S) or vaginal progesterone (V). At the end of the cycle (on the day of beta-hCG), a survey for determining the level of satisfaction will be administered and filled in by the patient during the waiting time and always before the knowledge of the result. This practical organization allows the elimination of emotional biases correlated with the outcome. In case of a negative beta-hCG, the patient will be scheduled for a second IVF/ICSI cycle after a washout (W) period (between 2 and 6 months). In the second cycle, the patient will undergo, during the luteal phase, the opposite treatment (V or S). Also in this case, the survey for evaluating the level of satisfaction will be administered on the day of beta-hCG, with the same modalities of the first cycle. The domains of the surveys are focused on facility of the administration, comfort, level of complaint, side effects, overall level of satisfaction.

The sequence S-V or V-S will be randomly assigned (random assignment) with the concealment of the allocation.

In case of a negative beta-hCG also in the second cycle, a post-hoc comparison between the two treatments will be carried out through a Semantic Differential Scale, in the "follow-up" phase.

• Progesterone 25 MG subcutaneous (Drug), also known as Pleyris: A single subcutaneous administration per day from the day of oocyte retrieval
• Micronized progesterone 200 MG (Drug), also known as Prometrium: 3 vaginal administrations per day from the day of oocyte retrieval
• recombinant FSH (Drug), also known as Gonal-f: Controlled ovarian stimulation (COS)
• Cetrorelix Acetate (Drug), also known as Cetrotide: Inhibition of Luteinizing Hormone (LH) premature surge during COS

Primary outcomes

• Surveys for testing the satisfaction [Single administration at the end of each treatment cycle (an average of 28 days)]: Patient's level of satisfaction will be measured as score on 5-point likert scale + 2 qualitative response

Secondary outcomes

• Semantic Differential Scale [Single administration at the end of two treatment cycles (an average of 130 days)]: Patient's preference of treatment measured on a 7-point likert scale

Sex: Female, ages: 18 Years to 44 Years

Inclusion Criteria:

first IVF/ICSI attempt (at the enrolment), regular menstrual cycles (25-33 days), controlled ovarian stimulation performed with Gonadotropin Releasing Hormone (GnRH) antagonists and gonadotrophins (recombinant FSH)

Exclusion Criteria:

systemic diseases, chronic medical therapies, pregnancy in one of the IVF/ICSI cycles, embryo "freeze all" strategy in one of the IVF/ICSI cycles for preventing Ovarian Hyperstimulation Syndrome (OHSS)

• Beltsos AN, Sanchez MD, Doody KJ, Bush MR, Domar AD, Collins MG. Patients' administration preferences: progesterone vaginal insert (Endometrin(R)) compared to intramuscular progesterone for Luteal phase support. Reprod Health. 2014 Nov 11;11:78. doi: 10.1186/1742-4755-11-78. PMID 25385669
• van der Linden M, Buckingham K, Farquhar C, Kremer JA, Metwally M. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev. 2015 Jul 7;2015(7):CD009154. doi: 10.1002/14651858.CD009154.pub3. PMID 26148507
• Yanushpolsky E, Hurwitz S, Greenberg L, Racowsky C, Hornstein M. Crinone vaginal gel is equally effective and better tolerated than intramuscular progesterone for luteal phase support in in vitro fertilization-embryo transfer cycles: a prospective randomized study. Fertil Steril. 2010 Dec;94(7):2596-9. doi: 10.1016/j.fertnstert.2010.02.033. Epub 2010 Mar 27. PMID 20347079

• Adolfo Allegra, MD, Principal investigator, Andros Day Surgery Clinic