In Vitro Fertilization and Preimplantation Genetic Diagnosis

Physicians at Penn Fertility Care are using preimplantation genetic diagnosis (PGD) to determine whether embryos produced by in vitro fertilization (IVF) carry the genes for a specific genetic diseases (such as cystic fibrosis, muscular dystrophy, etc). PGD permits diagnosis to be made before embryos are transferred to the uterus for the establishment of a pregnancy, thus greatly reducing the risk that a couple will pass the disease on to their child. PGD can also be used to determine if embryos produced by IVF have chromosomal disorders that would otherwise lead to pregnancy loss or result in the birth of a child with impairment, deformity and/or mental retardation. PGD is offered at Penn primarily to couples when one or both partners are carriers for a known genetic disease or have chromosomal abnormalities, such as translocations. In all these situations, PGD reduces the risk of achieving a pregnancy that will have the chromosomal abnormality or be affected by the genetic disease. At Penn Fertility Care, the process of PGD is initiated following the in vitro fertilization of multiple ova (oocytes/eggs). Typically, one or two cells are safely removed from each embryo at an early stage of development (Figure 1). Next, the cells are analyzed using a powerful genetic amplification technique called fluorescence polymerase chain reaction (F-PCR) that has the capacity to make millions of copies of the piece of DNA of interest for a reliable diagnosis. The product from the F-PCR reaction is then tested for the presence or absence of the known parental mutation(s) using a range of genetic techniques. To detect abnormalities in chromosomal number or structure, a technique called fluorescent in situ hybridization (FISH) uses fluorescent dye probes to identify specific regions in a chromosome. The chromosomes are then analyzed under a microscope that can distinguish normal chromosomes from cells with an unbalanced translocation or an abnormal number of chromosomes. The results of the tests are reported by the morning of the day of embryo transfer (five days after oocyte retrieval). The best quality embryo(s) from those that are not affected by genetic disease are selected for transfer to the uterus. If additional good quality, unaffected embryos are available, they may be cryopreserved for a future embryo transfer.

Case Study
Mrs. R, a 39-year-old woman was referred to Penn Fertility Care for PGD to improve the likelihood that she would have a healthy child after genetic testing revealed that she and her partner were carriers of SMA (spinal muscular atrophy 1). An inherited disease that causes severe, progressive muscle weakness, SMA is untreatable; affected infants generally live for two years or less. Together, Mrs. R and her partner had one healthy child. The couple then conceived a second child who had SMA and died a few months after birth. In a subsequent pregnancy, Ms. R underwent early chorionic villus sampling (CVS) at 11 weeks gestation and found that the fetus was affected with SMA. The couple chose not to continue this pregnancy. Wanting to avoid having another child with SMA, they then consulted specialists at Penn Fertility Care for conception options, including preimplantation genetic diagnosis. The couple elected to proceed with IVF with PGD. They conceived after two cycles of IVF and had a baby girl who did not have SMA.

Additional Options at Penn Fertility Care for Couples with Heritable Disorders

Through the Division of Reproductive Genetics, Penn Fertility Care offers an array of prenatal genetic testing options for couples with a personal or family history of genetic disease. In addition to PGD, these tests include:

• Amniocentesis
• Chorionic villus sampling
• Serum Screening for down syndrome and neural tube defects
• First trimester and sequential screening for Down syndrome
• Carrier screening for inherited conditions such as cystic fibrosis
• Ultrasonography to detect fetal anomalies

The Division of Reproductive Genetics also provides comprehensive diagnostic services, medical management, counseling and follow-up care for individuals and families who are affected by or concerned about genetic disorders.

Team of Faculty
Penn Fertility Care physicians provide compassionate intervention, goal-oriented reproductive care and experience in male and female fertility diagnosis and treatment. Services include:

• In vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and other assisted reproductive technologies
• Egg Donation Program for egg recipients and donors*
• Reproductive surgery
• Penn Polycystic Ovary Syndrome (PCOS) Center
• Reproductive options for cancer patients
• Pre-implantation genetic diagnosis (PGD)
• Adolescent reproductive health
• Management of endometriosis and fibroids

With a certified, on-site laboratory, Penn Fertility Care is at the forefront of research to develop new infertility treatments and to improve patient care. The staff is renowned for their research contributions to the field.
*The egg donation program at Penn Fertility Care is under the direction of Christos Coutifaris, MD, PhD, the Nancy and Richard Wolfson Professor of Obstetrics and Gynecology and Chief of the Division of Reproductive Endocrinology and Infertility.

Performing Preimplantation Genetic Diagnosis at Penn Fertility Care
Anuja Dokras, MD, PhD Medical Director, In Vitro Fertilization Program Associate Professor of Obstetrics and Gynecology Susan Troncelleti, MSN, CRNP PGD Clinical Nurse Coordinator

Access

Penn Fertility Care
8th Florr
3701 Market Street
Philadelphia, PA 19104

Penn Fertility Care at Pennsylvania Hospital
7th Floor
801 Spruce Street Spruce
Philadelphia, PA 19107

Penn Fertility Care at Penn Health for Women
Penn Medicine Radnor
250 King of Prussia Road
Radnor, PA 19087

To refer a patient and/or consult with a physician: Call 800-789-PENN (7366) or visit: PennMedicine.org/referral

Fertility Research at Penn
Fertility research at Penn Medicine is devoted to increasing the understanding of human reproduction as it relates to fertility regulation, female and male infertility and women’s health issues with the goal of improving the health and well-being of women and their families and improving outcomes. To this end, the research conducted by the Reproductive Research Unit at Penn Fertility Care and Penn’s Women’s Health Clinical Research Center includes NIH-funded clinical trials and research on fertility, polycystic ovary syndrome, fertility preservation after cancer, and contraception.

For a complete list of active clinical trials in women’s health and reproduction, please visit pennmedicine.org/fertility/research.
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