Indications for ART
As mentioned previously, in vitro fertilization is the most common assisted reproductive technology procedure performed. Although in vitro fertilization was originally designed to treat tubal disease, it is now utilized as a treatment for many causes of infertility. In addition to tubal factor infertility, other indications include endometriosis, male factor infertility, ovulatory disorders, unexplained infertility, ovarian failure, and a history of inheritable disease.
Tubal disease accounts for approximately 13.6% of indications for assisted reproductive technology procedures in the US. Some patients with mild distal tubal obstruction may benefit from reconstructive surgery prior to proceeding with vitro fertilization. However, the pregnancy rates in general are lower than with vitro fertilization, and the risk of ectopic pregnancy is greater. In vitro fertilization is the recommended treatment for women who remain infertile after one year following reconstructive surgery. For women with severe distal tubal disease, in vitro fertilization is the primary treatment. There is substantial evidence that pregnancy rates are improved in women who have surgical removal of hydrosalpinges prior to undergoing vitro fertilization. In one meta-analysis of three randomized controlled trials, the odds of pregnancy (OR = 1.75, CI 1.07-2.86) and of ongoing pregnancy and live birth (OR= 2.13, CI 1.24-3.65) were increased with laparoscopic salpingectomy for hydrosalpinges prior to vitro fertilization. The mechanism of this effect is not well understood, but fluid from the hydrosalpinges is inflammatory and may have a toxic effect on the embryo or the endometrium.
Proximal or mid-tubal obstruction is also an indication for in vitro fertilization. The most common reason for proximal obstruction is previous tubal sterilization. Microsurgical tubal reanastomosis can be effective in select candidates, although in vitro fertilization may be a better choice for women who are poor surgical candidates and those who only desire one additional pregnancy.
Endometriosis accounts for approximately 6.7% of indications for assisted reproductive technology in the US. Mild, moderate, and severe endometriosis has been shown to decrease fertility rates in women undergoing both intrauterine insemination and in vitro fertilization Pregnancy rates in patients with endometriosis have been demonstrated to have an approximate 45% reduction in pregnancy rates with vitro fertilization. Women with moderate and severe disease have a worse prognosis than those with mild and minimal disease. The proposed mechanisms include distorted anatomy (adhesive disease), abnormalities with oocyte development, and diminished endometrial receptivity. Although surgical management is an option for infertility treatment in women, in vitro fertilization is often the treatment of choice in women who are older, those with other infertility diagnoses, or previous treatment failures.
Male Factor Infertility
Male factor infertility as a single reason accounts for approximately 18.8% of indications for assisted reproductive technology in the US. Male factors can contribute to infertility in up to 35% of couples. The vast majority of sperm problems can be detected by a simple semen analysis. In men with mild semen abnormalities, intrauterine insemination with washed and concentrated sperm may be effective. In patients who fail to conceive after intrauterine inseminations with ovulation induction, the next step in treatment is vitro fertilization. In vitro fertilization allows an assessment of whether fertilization occurs. In cases of no fertilization, intracytoplasmic sperm injection (intracytoplasmic sperm injection) is then indicated. In men with severe abnormalities (references vary), poor fertilization is often expected. In this instance in vitro fertilization is indicated as a first line therapy with the addition of intracytoplasmic sperm injection. The indications for intracytoplasmic sperm injection remain controversial but often include the following parameters:
• Total motile sperm count <1 million
• <4 % normal morphology
• Previous in vitro fertilization cycle with no or poor fertilization
• Epididymal or testicular spermatozoa
Because the manipulation with intracytoplasmic sperm injection overrides potential natural protection to prevent fertilization by sperm with damaged DNA, there is the potential that children born after intracytoplasmic sperm injection might be at increased risk for congenital birth defects and/or chromosomal abnormalities. However, most studies to date have failed to identify any increased incidence of major malformations above baseline in children born after intracytoplasmic sperm injection.
Chronic anovulation is a common cause of infertility and accounts for 6% of indications for assisted reproductive technology procedures in the US. In most women with chronic anovulation, polycystic ovarian syndrome is the cause. Polycystic ovarian syndrome is a disorder characterized by hyperandrogenism and anovulation. Many women with polycystic ovarian syndrome are also very obese and may have insulin resistance. The majority of these patients will respond to conventional ovulation induction (clomiphene or gonadotropins). In women who are obese or insulin resistant, their response to ovulation induction may be enhanced with the use of insulin sensitizing agents such as metformin. When these treatment regimens fail, in vitro fertilization is a reasonable and useful option. Although women with polycystic ovarian syndrome (polycystic ovarian syndrome) often obtain a larger number of oocytes during retrieval, there appears to be a lower fertilization rate, presumably due to the endogenous hormonal imbalance. Despite a reduced fertilization rate, in vitro fertilization pregnancy rates in women with polycystic ovarian syndrome are comparable to ovulatory women. Women with polycystic ovarian syndrome who have high estradiol levels and a large number of preovulatory follicles are particularly at risk for the development of a syndrome called ovarian hyperstimulation syndrome (OHSS) because of their exaggerated response to gonadotropins. Women with a polycystic ovarian syndrome like response to gonadotropins are also at risk. Typical symptoms of ovarian hyperstimulation syndrome include abdominal distension as a result of fluid shifts from the vascular space to body cavities, dehydration, nausea, and shortness of breath, weight gain, and pelvic pain. Depending on the severity, ovarian hyperstimulation syndrome may be treated conservatively with fluid restriction or with paracentesis (removal of fluid from the abdominal cavity).
Although the exact prevalence of unexplained infertility is unknown due to differing diagnostic criteria, it ranges from 10-30%. In 2002, unexplained infertility accounted for 11.1% of indications for assisted reproductive technology procedures in the US. The highest success rates for treatment are with in vitro fertilization (28.5%). As one might expect, the success rates decrease in all forms of treatment as maternal age increases.
Diminished Ovarian Reserve
Diminished ovarian reserve is a common diagnosis in assisted reproductive technology centers and accounts for approximately 6.7% of indications for assisted reproductive technology in the US. Diminished ovarian reserve implies that the ability to produce eggs is reduced. Causes of diminished ovarian reserve may include surgery, congenital abnormalities and advancing maternal age. Many women with diminished ovarian reserve will be diagnosed by ovarian reserve testing or after a previous stimulation cycle demonstrates production of low numbers of oocytes.
Other Indications for ART
Women who have a family history of an inheritable disease may be candidates for in vitro fertilization with preimplantation genetic diagnosis (PGD). Preimplantation genetic diagnosis is most often utilized in this scenario when there is a single-gene disorder, sex-linked disorder, autosomal recessive disorder, or balanced translocation. Preimplantation genetic diagnosis is also utilized in some women with recurrent pregnancy loss, but the data are not clear regarding improved outcomes. To perform preimplantation genetic diagnosis one or two cells are removed from the embryo. These cells may then be analyzed for the presence or absence of a single gene order or for the presence of the correct number of chromosomes. This will enable couples to preconceptually evaluate embryos so that they can preferentially transfer those embryos that are not affected with a genetic disease or that have a normal chromosomal number. Preimplantation genetic diagnosis is occasionally used for sex selection and family balancing, but this is highly controversial.
Donor oocytes are indicated when a woman has premature ovarian failure, has undergone natural menopause or if a woman has demonstrated poor oocyte recovery and embryo quality with her own eggs. The latter indication is most often seen in women of advanced maternal age.
Women who have Mullerian anomalies (congenital absence of the uterus and vagina) are often candidates for gestational carriers (surrogates). Likewise, women with severe uterine abnormalities (fibroids, adhesions) or a previous hysterectomy may also be candidates for gestational surrogacy. Because the success rates for in vitro fertilization are so high, other techniques such as GIFT (Gamete intrafallopian transfer) and ZIFT (Zygote intrafallopian transfer) are rarely used. Occasionally, GIFT is performed for religious preferences. MESA and TESE are clearly performed for severe male factor infertility and oligo- or azoospermia. Assisted hatching is controversial and is used to potentially improve implantation rates. It is most frequently utilized in couples with recurrent failed cycles or prolonged in vitro culture, when a thickened zona pellucida is suspected.