Host Uterus (Gestational Carrier) vs Patient’s Own Uterus

The use of a host uterus or gestational carrier can be effective in situations in which the intended mother has no uterus, or there exists severe congenital anomalies, myomas, adenomyosis, intrauterine adhesions, incompetent cervix or medical problems which preclude or make very unlikely a successful outcome using their own uterus. In 1996 a total of 688 cycles were initiated and the live birth rate was 27.2% per initiated cycle. Again, careful attention to informed consent, counseling, and legal issues is mandatory.

A Practice Committee Report

Preimplantation Genetic Diagnosis

BACKGROUND

The ability to exclude embryos obtained in vitro which have diagnosed genetic deficiencies before the initiation of pregnancy offers an attractive means of preventing inheritable genetic disease. Currently couples who are carriers of genetic disease undergo chorionic villus sampling in the late first trimester, or amniocentesis in the second trimester, or post natal genetic testing to determine whether or not their offspring will be affected. The advantage to diagnosing these genetic abnormalities in the embryo avoids the 25-50% risk of a pregnancy having to be terminated. It has been 9 years since the first reported pregnancies using preimplantation genetic diagnosis have been achieved and over several hundred babies have been born world-wide using these techniques. This document reviews the literature of preimplantation genetic diagnosis, its experimental nature, the concerns about the safety of the procedure, the potential misuses of this technology, and the accuracy of the method.

SOURCES AND METHODS

There are numerous publications regarding technical aspects of preimplantation genetic diagnosis as well as specific diagnoses.¹ There are numerous manuscripts assessing accuracy and very few on safety. The information in this document represents a literature review of pertinent manuscripts describing preimplantation genetic diagnosis.

RESULTS

The clinical experience of preimplantation genetic diagnosis is worldwide but limited to few centers. However, many centers performing PGD have not reported their experience nor has there been any systematic approach to presenting errors. Therefore the literature is confined to those who choose to report and lacking in a complete experience of the technique.² Needless to say there have been enough informal reports to estimate an error rate in the 1- 10% range depending on the particular disease and assay being evaluated.

The initial experience involved gender determination of embryos as an indirect method to avoid X-linked genetic diseases such as hemophilia, muscular dystrophy, X-linked mental retardation, Lesch-Nyhan syndrome, adrenoleukodystrophy and others. These techniques utilized chromosome specific amplification using polymerase chain reaction (PCR) which is complicated by the possibility of DNA contamination and misdiagnosis. Fluorescent in situ hybridization bypasses this problem but is potentially limited by hybridization errors with subsequent misdiagnosis. Currently , it is possible to say that the error rate is quite small with these two techniques but the limited data thus far predicts a less than 1% error rate for gender determination.

Single gene defect disorders have been diagnosed use PCR and heteroduplex formation or PCR and restriction endonuclease digestion both of which distinguish normal from mutant alleles. The number and scope of the diagnoses performed is broad-examples such as cystic fibrosis, Tay Sachs, Marfan’s Syndrome, thalassaemia, muscular dystrophy , sickle cell and fanconi’s anemia.³ The concept of allelic dropout, where one of the two alleles selectively amplifies thus contributing to diagnostic errors is well described.⁴ There have been reports of this phenomenon in as much as 30% of blastomeres, although most have reported much lower numbers (0.3-5.6%). Perhaps, fluorescent PCR, which is more sensitive, may reduce this even further.

There have been more than 200 babies born by this procedure worldwide thus far. To date there are no reports of increased fetal malformation rates or other measurable, identifiable problems, however, a systematic follow up needs to be done.₅ The International Working Group is initiating such an effort but confidentiality issues and selective reporting will remain a continuing problem.

CONCLUSIONS

PGD appears to be a viable alternative to postconception diagnosis and pregnancy termination. The procedure is limited to certain genetic diseases and at centers where expertise in molecular genetics and embryology coexist. It is imperative that patients be aware of the uncertainty in diagnostic error and the unknown long-term consequences of this procedure on the fetus.

REFERENCES

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Grifo JA, Dietz HC, Tang YX, Adler A, Berkeley AS, Krey, L , et al. Preimplantation genetic diagnosis of Marfan’s syndrome using single cell PCR and restriction endonuclease digestion. J Assist Reprod Genet 1997;8:441.

Handyside AH, Lesko JG, Tarin JJ, Winston RML, Hughes MR. Birth of a normal girl after in vitro fertilization and preimplantation genetic diagnosis testing for cystic fibrosis. N Engl J Med 1992;327:594-598.

Grifo JA, Tang YX, Cohen J, Gilbert F, Sanyal MK, Rosenwaks Z. Ongoing pregnancy in a hemophilia carrier by embryo biopsy and simultaneous amplification of X and Y chromosome specific DNA from single blastomeres. JAMA 1992;6:727-729.

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