Assisted Reproductive Technologies (ARTs) are required when the barriers to fertility are otherwise insurmountable. These conditions may include severe tubal (pelvic) factors (irreparable nonfunctional fallopian tubes), severe male factors (fertilization must be microscopically assisted), and severe egg factors (donor egg required since ovulation induction is impossible). Recently, common indications for IVF have expanded to also include endometriosis, less severe tubal and male factor infertility, immunologic infertility, Diethylstilbestrol exposure in utero, and unexplained infertility.
Tubal factor infertility was the initial indication for IVF. Surgical success (in terms of reestablishing fertility) is generally poor after correcting severe pelvic adhesions (frozen pelvis), bilateral tubal occlusion with large (greater than 3 cm diameter) hydrosalpinges or a loss of the tubal internal architecture (rugae or fimbriae), previously failed tubal reconstructive surgery (especially if performed by an experienced fertility surgeon), prior bilateral salpingectomy (surgical removal of the fallopian tubes), and prior tubal ligation using a destructive technique (removal of fimbriae, implantation of the tubal stumps under the serosa of the uterus, extensive cautery).
If IVF is chosen for severe pelvic factor infertility, there is ample evidence that hydrosalpinges (if present) should be removed (or at least a tubal ligation performed) prior the IVF cycle to improve (implantation and) the pregnancy rates.
Severe male factor infertility can often be overcome using ARTs. When there is a low probability of fertilization using techniques that include standard microdroplet IVF (50,000 to 100,000 sperm placed in culture with one egg which has an intact zona [shell] in a small droplet of media) the microsurgical assisted fertilization techniques (PZD, SUZI, ICSI) are often suggested. In IVF centers performing ICSI routinely, fertilization (and pregnancy) rates with live mature sperm approach those of non-male factor IVF.
For men who have a limited supply of sperm (including men who have banked their sperm prior to radiation therapy or chemotherapy for malignant disease and men with outflow tract obstructions requiring microsurgical aspiration of sperm from the epididymis) IVF with assisted fertilization is also appropriately suggested. In men with few or no mature sperm available, testicular biopsy and use of immature sperm with assisted fertilization (during IVF) is now being developed with increasing success rates.
Severe egg factors that are not effectively treated with fertility medication include premature ovarian failure, menopause, and anovulation following radiation therapy or chemotherapy for malignant disease. In these situations, donor egg IVF or adoption may be appropriately considered.
Infertility associated with endometriosis can often be approached successfully with minimally invasive surgery. Aggressive surgical management of endometriosis is very time consuming and often difficult work, however, the success that can be achieved is equally rewarding. The additional time, surgical talent and responsibility (surgical risk) often required to adequately treat endometriosis surgically may be partially responsible for the frequent suggestion to (more simply) bypass the pelvic structures through IVF. However, the (out of pocket) expense of the IVF procedure, risk of a higher order multiple pregnancy, and the risk of ovarian hyperstimulation syndrome are major disadvantages with (simply moving to) IVF for all endometriosis patients.
Immunologic infertility is poorly understood. The best characterized immunologic cause of infertility relates to antisperm antibodies, which can be detected directly (expensive) using immunobeads, indirectly by the postcoital test, or inferred from a history of vasectomy reversal or significant testicular trauma. Treatment options include antibiotic treatment of a coexisting genital tract infection (if present), intrauterine inseminations, immunosuppressive therapy, and ARTs. Immunosuppressive therapy is potentially hazardous and doses (time course, etc.) have not been well established, so I discourage this option for my patients. If several cycles of IUI have failed to achieve a pregnancy then I consider COH/IUI or IVF.
Diethylstilbestrol (DES) was sometimes used (in the USA) during pregnancy until 1971, when the FDA recognized the increased risk of (otherwise rare) clear cell adenocarcinomas (of the cervix and vagina) in female offspring. The reproductive system of women exposed to DES in utero is at increased risk for fetal wastage, including recurrent miscarriage, ectopic pregnancy, incompetent cervix, and preterm labor. The IVF pregnancy rates for women exposed to DES in utero appear to be similar to women with tubal disease.
The two treatment options for women with unexplained infertility that have been shown to be clinically useful are COH/IUI and IVF. I generally suggest a few cycles of COH/IUI and if unsuccessful then IVF. The IVF success rates for these couples is equivalent to (or slightly greater than) those for tubal factor infertility.