The possible role of natural cycle and modified natural cycle in IVF

Abstract

1. Natural cycleThe first successful pregnancy and live birth resulting fromIVF were achieved during an unstimulated natural cycle(1). Soon thereafter, natural IVF was replaced by stimulatedIVF because of the very high cancellation rates of naturalcycles, and stimulated treatment became the standard inIVF. However, ovarian stimulation is not free from negativeconsequences and risks, including ovarian hyperstimulationsyndrome. (OHSS), which affects up to 5–10% of IVF cyclesand can be life-threatening (2). Multiple pregnancies occurin approximately 30% of pregnancies in patients who under-go the COH protocol and this phenomenon is related to in-creased risks of pregnancy loss, obstetrical complications,prematurity and neonatal morbidity with long-term damage.The long-term side effects however remain largely unknown.Ovarian cancer and gestational trophoblastic disease may beassociated with the chronic use of gonadotrophins (3). Nev-ertheless, the interest in natural IVF cycle treatment hasbeen renewed in recent years because of the increased effi-ciency of IVF technology. With the increasing awarenessof side effects of ovarian stimulation and better understand-ing of ovarian physiology in relation to ovarian folliculargrowth and maturation, IVF in natural cycles has gainedgreat attention and interest for both normal responder andpoor responder patients (4).1.1. AdvantagesNatural IVF cycles are simple, inexpensive and rapid andside effects associated with ovarian stimulation are elimi-nated. Natural cycle offers a more physiological, less drug-oriented, lower risk and more patient-friendly approach(4). Natural IVF cycles might be more efficient for obtainingideal embryos. It can be repeated on a monthly basis, andthe overall chances of success are therefore higher. Some pa-tients might prefer several successive natural IVF cycles in-stead of stimulated IVF cycles, which can only be repeatedonce a month (5). It has been reported that the clinical preg-nancy rate with stimulated IVF has reached approximately25–30% (6). However, repeated stimulated cycles shouldspan over several months to allow for the ovaries to recover.Further, if stimulated IVF cycles are repeated, the pregnancyrate will obviously decrease.1.2. DisadvantagesProblems related to natural IVF cycles include an increasedrisk of untimely LH surge and the possibility that no oocyteis retrieved and no embryo is available for transfer (5). Theefficacy of natural IVF is hampered by the high incidence ofoocyte retrieval failure (16.7–71.4%) and the relatively lowpregnancy rate per embryo transfer (ET) cycle (0–23.5%)(4). Natural IVF cycles resulted in an ongoing pregnancyrate of approximately 7% per started cycle and approxi-mately 16% per ET (7).1.3. Natural cycles in poor respondersPrevious studies found that the natural cycle works at leastas well as the COH in poor responder women who failedprevious ovarian hyperstimulation (8). In poor responder pa-tients, only very few follicles can be recruited and very fewoocytes can be retrieved after stimulation despite the highdose of gonadotropins administered or repeated stimulatedcycles performed and their management remains a challengein assisted reproduction. The majority of poor responderwomen had advanced reproductive age, diminished antral