Clinical Review

FERTILITY

OBG Manag. 2007 February;19(2):37-76

References

1. Practice Committee. American Society for Reproductive Medicine. Definition of “infertility.” Fertil Steril. 2006;86(Suppl 4):S228.-

2. Practice Committee, American Society for Reproductive Medicine. Aging and infertility in women. Fertil Steril. 2006;86(Suppl 4):S248-252.

3. Practice Committee, American Society for Reproductive Medicine. Optimal evaluation of the infertile female. Fertil Steril. 2006;86(Suppl 4):S264-267.

4. Practice Committee, American Society for Reproductive Medicine. Smoking and infertility. Fertil Steril. 2006;86(Suppl 4):S172-177.

5. Practice committee, American Society for Reproductive Medicine. Use of clomiphene citrate in women. Fertil Steril. 2006;86(Suppl 4):S187-193.

6. Male Infertility Best Practice Committee, American Urological Association, and Practice Committee, American Society for Reproductive Medicine. Report on optimal evaluation of the infertile male. Fertil Steril. 2006;86(Suppl 4):S202-209.

7. Christiansen OB, Andersen A-MN, Bosch E, et al. Evidence-based investigations and treatments of recurrent pregnancy loss. Fertil Steril. 2005;83:821-839.

8. Jauniauz E, Farquharson RG, Christiansen OB, et al. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum Reprod. 2006;21:2216-2222.

9. Practice Committee, American Society for Reproductive Medicine. Intravenous immunoglobulin (IVIG) and recurrent spontaneous pregnancy loss. Fertil Steril. 2006;86(Suppl 4):S226-227.

10. Practice committee, American Society for Reproductive Medicine. Multiple pregnancy associated with infertility therapy. Fertil Steril. 2006;86(Suppl 4):S106-110.

11. Practice Committee, Society for Assisted Reproductive Technology and the Practice Committee of the American Society for Reproductive Medicine. Guidelines on number of embryos transferred. Fertil Steril. 2006;86(Suppl 4):S51-52.

12. Practice Committee of the American Society for Reproductive Medicine and the Practice Committee of the Society for Assisted Reproductive Technology. Preimplantation genetic diagnosis. Fertil Steril. 2006;86(Suppl 4):S257-258.

13. Practice Committee of the American Society for Reproductive Medicine and the Practice Committee of the Society for Assisted Reproductive Technology. Ovarian tissue and oocyte cryopreservation. Fertil Steril. 2006;86(Suppl 4):S142-147.

14. Ethics Committee of the American Society for Reproductive Medicine. Fertility preservation and reproduction in cancer patients. Fertil Steril. 2005;83:1622-1628.

Dr. Adamson reports no financial relationships with any company whose products are mentioned in this article. He receives grant/research support from IBSA, Serono, and ViaCell and is a consultant to ViaCell.

What the future holds

We can expect more elective single-embryo or single-blastocyst transfers as we gain further expertise in this area. However, this practice should be implemented carefully in selected patients to maintain adequate pregnancy rates while reducing multiple gestations.

The United States has the highest ART success rates in the world (approximately 40% higher than in Europe) despite a reduction in the number of triplet or higher-order pregnancies resulting in live births after ART—from 7.0% in 1996 to 2.4% in 2004. The twin rate has remained stable at approximately 30%, but should decrease as 1- and 2-embryo transfers become more common.¹¹

Preimplantation genetic diagnosis now has multiple applications

Preimplantation genetic diagnosis (PGD) is over 15 years old, and at least 1,000 babies worldwide have been born after its use, with no reports of increased fetal malformation or other problems.¹²

Two basic techniques are employed to analyze the genomic status of the 1 or 2 blastomeres usually removed from the 8-cell embryo on day 3 after fertilization:

Polymerase chain reaction (PCR) is used to amplify a specific DNA sequence harboring a mutation. A mismatch (eg, due to a genetic deletion) leads to differential migration on the gel, thus permitting diagnosis. The error rate, primarily due to allelic dropout, in which 1 of the 2 alleles selectively amplifies and thus contributes to diagnostic errors, is approximately 0.3% to 5.6%.
Fluorescent in situ hybridization (FISH) allows determination of the ploidy of a blastomere. Labeled probes bind to chromosomes and are viewed under a fluorescent microscope. The error rate is 1% to 10% for a variety of technical reasons.¹² Testing takes about 1 day while the embryos are developing to blastocysts, at which time those that are viable and tested to be normal are transferred back into the uterus.

Not just for gender determination

PGD initially was used to determine gender (by FISH) as an indirect method of avoiding X-linked genetic diseases such as hemophilia. The error rate for gender determination is less than 1%. Since then, single-gene-defect disorders have been diagnosed using PCR and heteroduplex formation or restriction endonuclease digestion, both of which distinguish normal from mutant alleles. PGD has been performed broadly to diagnose Tay-Sachs, Huntington’s disease, and hundreds of other diseases.

Testing for translocation by PGD has been especially useful and may reduce the risk of spontaneous abortion from as much as 95% to 13% if one of the parents is a known translocation carrier.

Still under investigation is the routine use of FISH to detect aneuploidy in cases of recurrent pregnancy loss. The use of FISH for gender selection for family balancing is not recommended by the ASRM.

More young women seek to preserve their fertility

Fertility preservation through ovarian tissue or oocyte cryopreservation or vitrification has recently been popularized by cancer survival consumer groups, the media, and other interests. In addition to cancer patients planning to undergo chemotherapy or radiotherapy, candidates for fertility preservation include women undergoing bone marrow or stem cell transplantation or oophorectomy (for a benign tumor, endometriosis, or prophylaxis) and patients with severe autoimmune disease needing chemotherapy.

In cancer patients, fertility is preserved using one of several methods:

shielding or moving the ovaries to a different anatomic site during radiation
use of gonadotropin-releasing hormone analogs or oral contraceptives during chemotherapy (unproven)
changes to chemotherapy regimen
IVF cycle followed by cryopreservation of embryos if the patient has a male partner or is prepared to use donor sperm (provided the oncologist confirms that ovarian stimulation and high estradiol levels are acceptable and there is time to undergo an IVF cycle before cancer treatment begins).

Unresolved issues

Concerns about cryopreservation of ovarian tissue in cancer patients^13,14 include the possibility of reseeding tumor cells after ovarian transplantation, malignant transformation of transplanted ovarian tissue, and the possibility of congenital abnormalities as a result of cryopreservation—although no increase has been found in the patients studied so far.

The pregnancy rate is low

For cancer patients, the preservation of ovarian tissue or oocytes yields pregnancy rates significantly lower than those observed with standard IVF procedures. For cancer patients facing chemotherapy, however, oocyte cryopreservation may be one of the few options available and is acceptable in experimental protocols approved by the institutional review board.

Physicians should inform cancer patients about the options for fertility preservation prior to treatment.¹⁴ We lack data to recommend ovarian tissue or oocyte cryopreservation for the sole purpose of circumventing reproductive aging in healthy women.¹³