By I. Lane Wong, M. D., F.A.C.O.G., Reproductive Partners Medical Group, Fountain Valley and Long Beach, California
Introduction: A key step in the high tech Assisted Reproductive Technologies (ART) such as In Vitro Fertilization (IVF) and Gamete IntraFallopian Transfer (GIFT) is the recruitment and development of several follicles that will yield a cohort of eggs.
This process is called Controlled Ovarian Hyperstimulation (COH). The usual goal is to recruit a cohort of around 5-12 follicles that will produce a similar number of eggs. In a natural cycle, several follicles are recruited and initiate development. However, as estrogen levels increase, negative feedback occurs and the brain (anterior pituitary gland) releases less Follicle Stimulating Hormone (FSH). This causes all but the strongest follicle to cease maturation. Thus, in a natural cycle, generally only the one “dominant” follicle ovulates, releasing one egg. COH is accomplished by administering injections of gonadotropins, either FSH and Luteinizing Hormone (LH), or FSH alone. This prevents the drop in FSH levels allowing not just a single follicle, but a cohort of follicles to continue to develop. The result is the availability of several eggs for ART.
With IVF, the eggs are then taken back to the laboratory where fertilization occurs “in vitro” by adding sperm or by Intracytoplasmic Sperm Injection (ICSI). With GIFT, the eggs are combined with sperm and placed in the fallopian tube to allow fertilization in the natural location.
Unfortunately, one may undergo a cycle with the hopes of undergoing IVF, IVF with ICSI, or GIFT only to discover that a “poor response” is occurring and a sub-optimal number of follicles / eggs are developing. The purpose of this article is to address the problem of poor response to COH and outline possible solutions.
Definition: There isn’t a universally accepted definition to “poor response” or “poor responder.” Research papers studying this problem have used various definitions including those based on early follicular phase follicle stimulating hormone (FSH) levels, number of mature follicles, maximum estradiol levels, total gonadotropin dose used for stimulation, or number of mature eggs retrieved. In clinical terms, a practical definition is the inability to achieve the maturation of more than 4 follicles / eggs.
Background: Before describing strategies and their rationale for overcoming sub-optimal COH, an understanding of the usual COH protocol also known as the “Long Protocol” is needed for comparison. The “Long Protocol” involves several steps (Figures 1, 2):
