Clinical Management of In Vitro Fertilization With Preimplantation Genetic Diagnosis

Ilan Tur-Kaspa, M.D.


Semin Reprod Med. 2012;30(4):309-322. 

In This Article

Abstract and Introduction


Patients who undergo in vitro fertilization (IVF) because of preimplantation genetic diagnosis (PGD) require different clinical management than those who come in because of infertility alone. PGD adds a "fourth dimension" to the emotional aspect of a patients' assisted reproductive technology treatment. It significantly decreases the number of embryos available for transfer by 25 to 81%, and therefore ovarian stimulation for IVF with PGD should be tailored individually, taking into account patients' safety and estimated ovarian reserve. Recent studies showed that with increased number of oocytes retrieved, the higher the chance to have an embryo transfer and normal cryopreserved blastocysts. With adequate ovarian stimulation, there is no cutoff for the numbers of oocytes/embryos needed to start PGD with, especially for younger patients. Patient-friendly protocols, such as those based on gonadotropin-releasing hormone antagonist and vaginal progesterone support may be used. Elective single embryo transfer and blastocysts cryopreservation to avoid multiple pregnancies may be offered with PGD. The benefit of adding preimplantation genetic screening to IVF treatment is still controversial, and evidence-based data on 24-chromosome testing of polar bodies or trophectoderm is needed before it may be implemented into routine patient care.
This review discusses the clinical management of IVF with PGD based on the best available data and my personal clinical experience as a reproductive specialist with >1000 IVF/intracytoplasmic sperm injection-PGD cycles. The information provided here will assist reproductive specialists, nurses, geneticists, genetic counselors, and embryologists to better counsel and treat couples who wish to conceive with a healthy child through IVF with PGD. It is time for PGD to be viewed as a modern modality of preventive medicine. As such, it should be incorporated into national health-care systems and be covered by medical insurance.


The use of genetic technology to avoid the birth of a child with a genetic disorder is in accordance with the ethical principles associated with physicians' therapeutic role.[1] Preimplantation genetic diagnosis (PGD) using in vitro fertilization (IVF) represents a major scientific advance for couples at risk of having children with heritable and debilitating genetic diseases.[2–5] PGD for couples who carry a balanced chromosomal translocation significantly decreases the risk of spontaneous miscarriage (up to <20%) and significantly increases live-birth rates.[2,6–10] The practice committees of the Society for Assisted Reproductive Technology and of the American Society for Reproductive Medicine published their opinion on PGD in 2008 and stated that "because the birth of the healthy child validates the efficacy of PGD, randomized controlled trials are not necessary."[2] At the same time it is highly recommended both in Europe and North America that couples be informed with detailed counseling on IVF/intracytoplasmic sperm injection (ICSI) procedures and risks, as well as the technical limitations of PGD. They should also be provided with realistic expectations for the number of the embryos they will have available for transfer and/or cryopreservation, as well as their chance to conceive and deliver a healthy infant.[2,3,11–13]

Several reproductive options are available for a high-risk couple to prevent passing on a genetic disorder to their offspring, so it is very important to examine how many couples would prefer PGD over other alternatives. It is clear now that most couples who carry a serious genetic disorder prefer to conceive with healthy embryos tested in vitro before implantation and thus avoid the very difficult dilemma of whether or not to terminate a pregnancy or deliver a sick child.[3] Musters et al[14] recently investigated the attitude of 960 couples with different genetic disorders toward PGD. Of the couples who wished to conceive, and if PGD would be performed without any significant delay, 80% preferred PGD over natural conception and prenatal testing. Even when delay in treatment of up to 1 to 2 years may occur (as may often may happen in Europe), because of lack of resources and time needed for PGD genetic setup, 74% of them still preferred to use PGD.

Most women would also prefer preimplantation genetic screening (PGS) as an alternative to prenatal testing for Down syndrome.[17] The benefit of adding PGS to IVF treatment is still controversial, and evidence-based data on 24-chromosome testing (of polar bodies or trophectoderm) is needed before it may be implemented into routine patient care.[2,12,14–16,18–28]

Since PGD was introduced in 1990 by Verlinsky et al[15] in Chicago with polar body biopsy and in London by Handyside et al that same year[16] with blastomere biopsy, its indications have expanded rapidly. Nevertheless, there are still questions to be answered regarding its clinical practice. This article discusses the safety of PGD procedures and children's outcome and reviews how to optimize ovarian stimulation and PGD success. The daily routine of clinical management of IVF for PGD, as well as special clinical dilemmas and protocols such as nondisclosure PGD, are examined.

The information provided here will assist reproductive specialists, nurses,[29] geneticists, genetic counselors, and embryologists to better counsel and treat couples who wish to conceive a healthy child through IVF with PGD. The potential for PGD to become a modern modality of preventive medicine is advocated.


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