Treatment

The International Committee for Monitoring Assisted Reproductive Technologies (ICMART) reported an estimated 1,929,905 ART cycles in 2014 from 2746 ART centers in 76 different countries. These ART cycles resulted in the birth of 439,039 babies during the reporting period. In the United States (U.S.) alone, a total of 203,119 ART cycles were performed in 456 U.S. fertility clinics in 2018. These cycles resulted in 73,831 live births. ART contributed to 2.0% of all infants born in the United States in 2018.

Indications forART

Louise Brown, the rst IVF baby in 1978, was born to a mother who underwent laparoscopic oocyte retrieval during the natural menstrual cycle and had a history of severe tubal disease requiring at least two prior laparotomies. Since then, at least nine million babies have been born worldwide using IVF for different infertility indications. The ART Fertility Clinic and National Summary Report from the CDC lists the following indications for all ART cycles in the U.S. during 2019: diminished ovarian reserve or ovulatory dysfunction (29%), male factor (27%), unexplained infertility (27%), tubal factor (10%), and endometriosis (7%).

Accelerated Utilization of ART

Ef cient ovarian stimulation protocols, standardization of a simple outpatient oocyte retrieval technique, and successful laboratory techniques, including intracytoplasmic sperm injection (ICSI) and vitri cation have often been recognized as the main reasons for the acceleration of ART utilization.

The success of IVF depends signi cantly on an individualized approach to ovarian stimulation (Fig. 30.2).

An ef cacious ovarian stimulation protocol maximizes follicular development, improves oocyte and embryo quality, increases implantation and live birth rates, and minimizes the risks of complications such as ovarian hyperstimulation syndrome (OHSS) and multiple pregnancies. The stimulation of multiple follicles with gonadotropins is associated with supraphysiologic estradiol (E2) levels, often inducing a premature luteinizing hormone (LH) surge, which historically was associated with IVF cycle cancelation. To circumvent the problem of a premature LH surge and/or ovulation in IVF cycles, co-administration of gonadotropin-releasing hormone agonists (GnRH-a) was introduced in the late 1980s. However, GnRH-a protocols were associated with higher rates of side effects, including mood changes, hot fushes, severe headaches, short-term memory loss, and OHSS. These shortcomings of GnRH-a protocols paved the way for potent gonadotropin-releasing hormone antagonists (GnRH-ant) in the early 1990s. GnRH-ant competitively binds to the GnRH

ART Success Rates

Using data from all reporting ART clinics in the U.S. in the year 2018, the Society for Assisted Reproductive Technology (SART) reported 42,460 IVF cycle starts in women <35 years, 26,642 IVF cycle starts in women 35–37 years, 25,430 IVF cycle starts in women 38–40 years, 13,345 IVF cycle starts in women 41–42 years, and 9507 IVF cycle starts in women >42 years of age. The corresponding live birth rates in these groups were 44.6%, 31.5%, 19.9%, 9.7%, and 2.9%, respectively. Approximately 93–96% of all ART-conceived babies were singletons. This is predominantly due to the utilization of elective single embryo transfers (SET). The national SET rate among all ART cycles was 74.1% in women <35 year, 72.8 in women 35–37 years, and 66.4% in women >37 years of age. Global trends also suggest increased SET rates from 30.0% in 2010 to 40.0% in 2014. The accelerated trend in SET cycles has occurred due to the preferential transfer of blastocyst-stage embryos over cleavage-­stage embryos. A recent meta-analysis of 32 randomizedcontrolled trials (RCTs) including 5821 couples reported higher odds of live birth (1.27, con dence interval 1.06–1.51) with the blastocyst-stage transfer when compared to cleavage-stage transfer, though this evidence was of low quality.

Recent Trends in ART

The past two decades has witnessed accelerated adoption of certain aspects of ART despite limited evidence. For example, even though ICSI is typically used for the treatment of male factor infertility, a surveillance study based on U.S. data found that ICSI use in non-male factor infertility increased from 15.4% to 66.9% between 1996 and 2012. More recent data suggest ICSI utilization rates of close to 80% even though 30% of IVF cases are for male factor infertility. These trends are not supported by multiple clinical studies showing no increase in fertilization or live birth rates with the use of ICSI for non-male factor infertility. Similarly, better vitri cation techniques and improvements in culture media has resulted in the proliferation of frozen-thawed embryo transfer (FET) cycles and preimplantation genetic testing (PGT) cycles. U.S. data indicate an 82.5% increase in FET cycles between 2006 and 2012, while the number of fresh embryo transfers has increased by only 3.1%. These data indicate that many IVF centers have preferentially shifted toward FET cycles. The theorized bene ts of FET over fresh embryo transfer have been propagated by the idea that the former provides a better implantation environment. However, recent multicenter randomized-controlled trials (RCTs) have highlighted that FET-associated improvements in pregnancy and perinatal outcomes are observed in the context of robust or exaggerated ovarian stimulation, such as women with polycystic ovarian syndrome (PCOS), and not in all women undergoing IVF. Finally, PGT-A has been heralded as a universal screening test for all women