P-555 Do IVF patients prefer the rectal route to the vaginal for luteal phase progesterone administration? - a cohort study
Authors: Brix Jensen M , Mikkelsen A , Kyndi M , Humaidan P , Alsbjerg B 
Published: June 2023

Abstract

Study question
How do IVF patients perceive rectal administration of progesterone for luteal phase support compared to vaginally administered progesterone?

Summary answer
Rectal administration of progesterone causes less discomfort in IVF patients, undergoing Hormone Replacement Therapy Frozen Embryo Transfer (HRT-FET) and is preferred compared to vaginal administration.

What is known already
Progesterone is essential for implantation and normal development of pregnancy in spontaneous pregnancies as well as in ART pregnancies. In IVF, progesterone is most often administered vaginally in Europe for luteal phase support, although, this route may cause cumbersome discharge, vaginal bleeding, and irritation of the vulva. For many years the vaginal route has been the gold standard, although, progesterone is well absorbed rectally and recent studies have shown that rectally administered micronized progesterone was well accepted among IVF patients. Until now, in IVF very little focus has been on patient convenience as regards luteal phase support.

Study design, size, duration
An interventional cohort study, conducted from January 2020 to November 2022 in a public fertility clinic. A total of 479 patients received a questionnaire (Q1) by e-mail during the period between the embryo transfer and the pregnancy test; A second questionnaire (Q2) was answered at the time of the first ultrasound scan in gestational week 7.

Participants/materials, setting, methods
Patients underwent an HRT-FET protocol, including vaginal progesterone (VP) (400mg/12hours). In patients with serum progesterone levels lower than 11 ng/ml on the 6th day of progesterone, additional progesterone was administered rectally (RP) (400mg/12hours) from that day until the day of pregnancy testing, and in pregnant patients until the first scan in week 7.
Side effects and patient convenience of both routes were reported in a questionnaire, including 27 questions, using a visual analog scale (0-100).

Main results and the role of chance
A total of 73% of HRT-FET patients (349/479) answered Q1 before the pregnancy test and a total of 27 % (93/349) of the cohort received progesterone both vaginally and rectally. The response rate of Q2 in gestational week 7 was 100 % (221/221) and a total of 28 % of patients (62/221) administered progesterone both vaginally and rectally.
In Q1, a total of 60% of patients (54/90) preferred RP over VP in the cohort of patients treated with both administration regimens.
In Q2, a total of 62% of patients (37/60) preferred RP over VP in the cohort of patients treated with both administration regimens.
The overall discomfort was lower in relation to RP in both questionnaires and, especially discharge was lower in RP compared to VP; median interquartile range (IQR) in Q1: 11 (3-23) vs. 50 (25-66) and Q2: 19 (9-28) vs. 47 (22-62), respectively. Changes in defecation pattern after RP were reported in Q1 as well as Q2, 48% (45/92) and 55% (34/61), however, the discomfort was reported as mild. An increased flatulence was reported by 50% (46/92) in Q1 and 63% (39/92) in Q2, however, again the discomfort was reported as mild.

Limitations, reasons for caution
Currently, it is unknown whether the present results apply to progesterone products other than the one used in the present study (Cyclogest®). The questionnaire used, although having been used in another published study with another progesterone product, was not specifically validated for this product.

Wider implications of the findings
The rectal route should be remembered for luteal phase support in IVF, and some patients might choose the rectal route over the vaginal for their luteal phase support due to less discharge.

Trial registration number
EudraCT no.: 2019-001539-29