In a recent analysis of SART, it was revealed that only 13 and 16 % of the clinics in the USA performed unstimulated IVF in 2006 and 2007, respectively, which only represented <1.5 % of the total cycles initiated at those clinics (Gordon et al. 2013).

In patients with an expected good response, the use of COH increases the risk for ovarian hyperstimulation syndrome (OHSS); on the other hand, the reduced number of ultrasounds in a natural cycle, (two or three per cycle) as well as the absence of hormonal medication, can make this procedure less expensive and emotionally easier. And when time is an important issue for the couples, in a natural cycle, there’s no need for waiting due to the recovery that the ovaries sometimes need as consequence of the hormonal stimulation, and doing the fresh transfer also provides results within that same cycle. Another issue is endometrial receptivity; one possible mechanism of impairment is advancement of the receptive phase due to the high hormonal levels achieved during COH, resulting in embryo–endometrium asynchrony (Shapiro et al. 2011), but this issue will be addressed further in this chapter.

Nargund et al. (2001) performed one of the most representative studies, in 2001, with 181 cycles and with 48 % of patients being >35 years old. It reported 81.6 % successful retrievals, with a pregnancy rate of 12.7 % per cycle and a cumulative rate after four cycles of 46 %. In patients <35 years old, more than half the initiated cycles (54 %) reached ET, with a pregnancy rate per ET of 35.9 %. The implantation rate was statistically higher in unstimulated IVF cycles compared with stimulated IVF cycle in patients between 35 and 42 years of age, and there was no significant difference in patients aged <35 years. There were no pregnancies from unstimulated IVF in those >42 years of age. For all ages, the clinical pregnancy rates per initiated cycle, retrieval, and transfer were 9.6 %, 13.5 %, and 26.1 %, respectively. Similarly, for all ages (including >42 years), the live birth rates per initiated cycle, retrieval, and transfer were 7.3 %, 10.3 %, and 19.9 %, respectively (Gordon et al. 2013).

In general, poor-responder women are the patients who, during controlled ovarian hyperstimulation for IVF, show poor follicle growth despite the high dose of medication administered and low levels of serum estradiol. The incidence of poor-responder patients is approximately 10 %, and it is often related to patient age (Schimberni et al. 2009). The management of these patients is still a challenge for many physicians, despite a number of options in protocols available.

Poor responder patients are usually refractory to stimulation protocols; although many treatment strategies have been suggested, the results remain poor, and despite the high quantity of gonadotropins administered, their chances of pregnancy remain very low (Schimberni et al. 2009). Their treatment is generally approached in different ways, either by trying different stimulation protocols using high levels of gonadotropins, changing the dosages or the use of GnRH analogs or antagonists, trying IVF in a natural cycle, or as a last resort, suggesting egg donation. However, egg donation is not an option for many patients who wish to try every option in order to have a child with their own eggs.

In a recent study, Schimberni et al. (2009), performed 500 natural cycles in 294 women considered poor responders. Oocytes were found in 391 cases of oocyte retrieval (78.1 %). After the ICSI procedure, cleaving embryos suitable for transfer were obtained in 285 cycles (57.0 %), but no fertilization or cleaving embryos were obtained in 106 cycles (21.0 %). Pregnancy was observed in 49 cases, with a pregnancy rate of 9.8 % per cycle, 17.1 % per transfer, and 16.7 % per patient.

There have been conflicting results by other groups; in 2004, Kolibianakis et.al. performed a study of 32 patients with FSH ≥12 IU/l, with discouraging results; 32.1 % of the cycles did not result in oocyte retrieval; in 16.9 % in which oocyte retrieval was performed, no oocytes were obtained, and embryo transfer was performed in 19 out of 44 cycles in which oocytes were retrieved (43.2 %), and no ongoing pregnancy was achieved in 78 modified natural cycles (MNCs) (Kolibianakis et al. 2004).

The fact that a large group of patients do not accept oocyte donation poses difficulties in generalizing the study findings, as this is a personal decision related to cultural or religious characteristics, and, ultimately, after proper counseling the decision has to be made by the patient herself.