Role of Triptorelin 0.1 mg as a Luteal Phase Support in Assisted Reproductive Technique After Embryo Transfer : a Randomized Controlled Trial

There is still controversy over the best LPS agent and protocol and its dose and duration as well as the time of initiation and cessation.

There are many protocols of luteal support in assisted reproductive technology (ART) cycles. Luteal phase support with progesterone is a standard approach for ART cycles .

Initial studies in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) patients have demonstrated that the use of a GnRH agonist (GnRHa) trigger, followed by fresh transfer and a standard luteal phase support (LPS) was associated with unacceptably high rates of loss in early pregnancy compared to hCG trigger, particularly in normal responder (NR) patients.

During IVF and fresh embryo transfer, the luteal function is disrupted and the success of the treatment is critically dependent on exogenous luteal phase support

During the last decade, two different modified LPS strategies have been proposed to overcome the mentioned luteal phase deficiency. One of these approaches has been called the "European approach" in which the endogenous steroid (progesterone and estradiol) production by the corpora lutea is boosted by exogenous LH activity, i.e., LH or hCG after GnRHa trigger. The other approach has been called the "American approach" in which luteal progesterone and estradiol are administered exogenously, thus, disregarding the function of the corpora lutea.

It has been subsequently concluded that this early pregnancy loss was caused by luteal phase (LP) insufficiency, despite the use of a standard LPS package of progesterone (P) and estradiol (E2). The LP defect was primarily caused by reduced early-mid-luteal luteinizing hormone (LH) activity, resulting in a significant reduction in progesterone output by the corpora lutea (CL) as no adverse effects were seen with respect to the maturity rate of oocytes, fertilization rates, embryo quality, and reproductive outcomes during the subsequent replacement of frozen embryos derived from women who had received a GnRHa trigger .

Transvaginal progesterone is commonly used for luteal phase support. Progesterone administration is initiated on the oocyte pick-up (OPU) day and continued for 12 days, until the serum beta human chorionic gonadotropin (hCG) measurement day. However, there are conflicting results regarding the dose, route of administration (oral, subcutaneous, transvaginal), duration (until the ultrasound demonstration of heartbeat in an intrauterine gestational sac, until 10 weeks of gestation, until 12 weeks of gestation), and formulations such as synthetic or micronized types of progesterone.

A bolus of GnRHa, when administered 6 days after OPU in GnRH antagonist cycles, is able to induce a surge of pituitary gonadotropins (FSH and LH), eliciting an increase in steroid production (E2 and P) by the CL.

The exact mechanism behind the presumed beneficial effect of LP GnRHa administration remains poorly defined. It has been hypothesized that GnRHa either supports CL function by inducing LH secretion by the pituitary gonadotrophic cells or stimulates the endometrial GnRH receptors.

Tesarik postulated a direct effect of GnRHa on the embryo, as suggested by an increase in β-HCG secretion.

Importantly, there are significant differences in the early-mid-LP endocrine pattern when GnRHa triggers and hCG triggers are compared, especially in terms of LH levels. From this, it could be hypothesized that the GnRHa-triggered IVF cycle could benefit more from the addition of a bolus of GnRHa to boost the circulating endogenous LH and thus, progesterone levels around the time of implantation than the hCG triggered cycle. No studies previously investigated this issue. Therefore, the aim here was to explore a possible fine-tuning of the LPS of GnRHa-triggered IVF/ICSI cycles, using the previously suggested protocol.

Significantly increased implantation rates (IRs) were previously reported in oocyte recipients as well as in patients who were triggered with hCG, if they received a single mid-luteal bolus of GnRHa in addition to standard LPS .

A beneficial effect of a single dose of GnRH agonist administration as a luteal phase supporting agent is yet to be determined because of the wide heterogeneity of data present in literature. Well-designed randomized clinical studies are required to clarify any effect of luteal GnRH agonist addition on pregnancy outcome measures with different doses, timing, and administration routes of GnRH agonists .

Administration of 0.1 mg of the GnRH agonist triptorelin on day 3 after embryo transfer led to a significant improvement in implantation rate (12.3% vs. 7.3%) and clinical pregnancy rate (25.5% vs. 10.0%) as compared with placebo.

Luteal phase support with single-dose GnRHa might be as efficient as three doses of hCG. Large prospective, randomized-controlled studies are required comparing GnRHa and hCG for luteal phase support.