Intrauterine insemination (IUI) is a common treatment for couples with subfertility with lower costs compared to in vitro fertilization (IVF). Clomiphene citrate, gonadotropins, and letrozole are used for ovulation induction in IUI cycles. Patients undergo controlled ovarian stimulation with these agents before the procedure in an attempt to increase the number of oocytes and eliminate ovulation disorders. Luteal phase is defined as the period between ovulation and the end of the menstrual cycle marked by either onset of the menstruation or onset of pregnancy. Following ovulation, the luteal phase of a natural cycle is characterized by the formation of a corpus luteum (CL) which secretes steroid hormones including progesterone (P) and estradiol (E2). If conception and implantation occurs, the developing blastocyst secretes human chorionic gonadotropin (hCG) for the maintenance of CL and its secretions. P is required for endometrial receptivity and its secretory transformation. Fertility treatments may interfere with the luteal phase via several mechanisms. Disruptions in the hypothalamic pituitary-gonadal axis as a consequence of supraphysiologic E2 levels caused by controlled ovarian stimulation lead to a shortened luteal phase with low concentrations of P. Therefore, in assisted reproductive technology (ART), ovarian stimulation with gonadotropins is associated with luteal phase deficiency which can be compensated with the luteal phase support.

Supraphysiologic E2 levels are often associated with multifollicular development during assisted reproductive technology (ART). Yet, during ovulation induction in IUI, only one to two dominant follicles may be achieved which makes the influence of mild ovarian stimulation on the corpus luteum function questionable. As a result, luteal phase support in IUI cycles has become a debatable issue with controversial findings in many different studies. The aim of this prospective controlled study by Mu¨ge Keskin and Rus¸en Aytaç was to assess the effect of luteal phase vaginal progesterone supplementation on β-hCG positivity and clinical pregnancy rates in women undergoing ovarian stimulation and IUI.
This prospective controlled randomised study was conducted at the Ankara University School of Medicine Infertility Center, a tertiary infertility center, from August 2014 to January 2015. 87 patients with unexplained infertility or male subfertility who were treated with ovarian stimulation and IUI using gonadotropins were enrolled.
Patients in the study group (n = 44) received luteal phase vaginal progesterone supplementation. Patients in the control group (n = 43) did not receive any luteal phase support.

After the evaluation of serum FSH, LH, estradiol, PRL, and TSH levels on the third day of the menstrual cycle. Ovarian response was assessed with transvaginal ultrasound (TV-US) from day 8 of each cycle. Cycles were triggered with 10.000 IU hCG when at least one dominant follicle had reached 17 mm in diameter. The IUI was performed 36 h after hCG administration. In the study group, luteal phase support was provided via vaginal administration of micronized progesterone capsules twice a day beginning on the day of insemination until the monitorizaton of fetal heart rates on TV-US. Patients in the control group did not receive any luteal phase support. Primary outcomes were β-hCG positivity and clinical pregnancy rates. β-hCG positivity was defined as increased serum hCG levels. Clinical pregnancy was determined as the presence of a gestational sac with embryonic viability on TV-US.
87 couples either with unexplained infertility or male subfertility were included in the study. There was no difference in duration of stimulation, total amount of gonadotropins, number of follicles with a diameter ≥17 mm, and endometrial thickness on the day of hCG between two groups. Types of gonadotropins used for stimulation were also comparable for follitropin α, follitropin β, and menotrophin between the two groups. hpHMG use was significantly higher in the control group. There was no statistical difference between control and study groups in terms of β-hCG positivity and clinical pregnancy rates.
In this prospective randomised controlled study, it was shown that in patients having ovarian stimulation with gonadotropins for IUI due to unexplained infertility or male subfertility, luteal phase support with vaginal progesterone is not associated with higher β-hCG positivity and clinical pregnancy rates compared with patients without luteal phase support.
In conclusion, it is well proven that stimulated IVF cycles require luteal phase support. Although luteal phase support in IUI cycles stimulated with gonadotropins is widely adopted, there is a lack of robust evidence. Study findings do not show any beneficial effect of luteal phase support in IUI cycles stimulated with gonadotropins. Further randomised trials with larger groups are required to examine the necessity of luteal phase support in IUI cycles.
Source: Mu¨ge Keskin and Rus¸en Aytaç; Hindawi Obstetrics and Gynecology International Volume 2020
https://doi.org/10.1155/2020/6234070