IVF stimulation in pregnancy: lessons to be learned with implications for the luteal phase start IVF cycle

Abstract

In vitro fertilization (IVF) has been widely used to treat infertile couples. Standardly, IVF protocols start stimulation in the early follicular phase [1]. Centers routinely perform ultrasound on cycle day 2 to 3 to evaluate the endometrial lining, rule out pregnancy, and verify a lack of functional ovarian cysts before starting controlled ovarian stimulation. However, the role of early follicular start is being questioned, with random and luteal phase stimulations being investigated, particularly in centers practicing freeze all protocols to favor implantation [1][2][3]. This is done for both convenience and in cancer patients desiring pre-chemotherapy fertility preservation, who must start urgently [4,5]. In a recent study, patients were divided into three groups based on menstrual cycle phase for commencement of stimulation: the conventional early follicular, late follicular phase, and luteal phase starts. All three groups were comparable in terms of the number of mature oocytes (MII), quantity of embryos and oocytes retrieved, implantation rates, and clinical pregnancy rates [2]. Clearly, a random start for IVF stimulation is interesting in that it will minimize time to initiate stimulation, particularly if the center will perform pre-implantation genetic testing type A or for implantation benefit, freeze all embryos, a trend, which is increasing, particularly in the USA.However, when luteal phase starts, one complication that may arise is that the patient could be unknowingly pregnant. The role of pregnancy on stimulation outcomes has not been investigated. However, we would anticipate that the body has mechanisms in place to prevent double fecundation at different time periods, which would result in two pregnancies of different gestational ages developing concurrently. The role of