May 2011 eNews
PGD for Genetic Disease: Reproductive Options for Couples At-Risk for Children with Hereditary Genetic Disorders
by Harvey J. Stern, MD, PhD, Director of Reproductive Genetics
Couples who are at-risk for having children with inherited genetic diseases face difficult reproductive decisions regarding their own families. They can avoid all risk by not having children or by adopting, or they can significantly reduce the risk by using a gamete (egg or sperm) donor. For those who wish to have children using their own gametes, the option of conception followed by prenatal diagnosis is available. This last option, however, can result in having to make the difficult and painful decision of whether or not to interrupt an ongoing pregnancy should a fetus be found on prenatal testing to be affected with a genetic disease. For some, this option is not acceptable due to personal moral or religious beliefs.
Many people feel that unless there are already people in their family who have a genetic condition, then it is unlikely that they are “carriers” of any such diseases. This reassurance is false. Studies have suggested that all of us carry genes for approximately seven significant recessive genetic disorders where both parents contribute an abnormal gene which they “carry” to the fetus. We all have two copies of our genes (one copy each from Mom and Dad). For recessive conditions, both genes a fetus inherits are abnormal, but the parents who have a normal gene and “carry” an abnormal gene are clinically normal. This is why recessive genes can be carried for generations in families without being known.
Some couples find out that they are carriers of a genetic disorder when a sibling or other relative gives birth to a child who is diagnosed with a genetic condition such as cystic fibrosis (CF). This information will often lead siblings or cousins to be tested to see if they are also carriers of CF. In other cases, people are at higher risk for carrying certain genetic diseases due to their ethnicity such as sickle cell disease in African-Americans or Tay Sachs disease in Ashkenazi Jews. The American College of Medical Genetics and The American College of Obstetrics and Gynecology have published recommendations for prenatal genetic screening for cystic fibrosis, Jewish genetic diseases, and inherited blood disorders. Finally, due to advancements in DNA technology, it is now possible to carry out screening for over 100 different genetic diseases simultaneously. This screening can be done before conception and at reasonable cost. This could result in more couples being aware of certain genetic risks before starting their families.
Preimplantation Genetic Diagnosis (PGD) was first developed for clinical use in 1990. PGD represents a specialized form of prenatal diagnosis in which the testing is performed on embryos created by In Vitro Fertilization (IVF) prior to implantation in the uterus. During an IVF/PGD cycle, a single cell is removed from each embryo on the third day of embryonic development. Each cell undergoes genetic testing to identify which embryos are and are not affected with a genetic condition such as cystic fibrosis or spinal muscular atrophy. In this way, only healthy embryos are returned to the uterus on the fifth day of development. If a pregnancy occurs, the resulting child has a very high (99%) chance of not having the disease. This likelihood is increased by creating multiple embryos through the IVF process.
At the current time, PGD can be performed for any genetic disorder where the gene sequence or the gene location of the disease-causing mutation is known. The main difference between PGD and genetic testing of blood or amniotic fluid is that in the latter there are millions of copies of DNA in the sample, but there is only one molecule of DNA in the single cell removed from the embryo. The laboratory staff who handle the samples take extraordinary precaution to avoid contaminating the samples with outside DNA. Otherwise, the test would yield the wrong result. In the early days of PGD such errors did occur. Today, the testing has improved by including linked DNA markers to the testing protocol. These are areas of DNA where the same sequence of 4 or 5 base pairs (either A, T, G, or C) are repeated in tandem up to hundreds of times. The actual number of repeats varies in different people; with most having two different sized repeats on the chromosomes inherited from their mother or father respectively. Most non-related individuals have different combinations of repeats associated with different areas of the chromosomes. In the laboratory, known repeats located very close to the gene of interest (for example the CF gene on chromosome 7) are identified from computer databases. DNA from the couple and other family members (such as an affected child) is analyzed. The critical disease-causing mutation is inherited from the parents along with a specific pattern of the linked repeats that is specific for each individual family. This DNA “haplotype” helps to unambiguously identify the chromosomes carrying the disease-producing genes as well as the chromosome carrying the normal gene.
From this information, the laboratory develops a test specific for the current patient containing a test for their actual disease-producing mutation along with the best two to three linked markers for that mutation. The development and validation of such a test often takes three months or more. The accuracy of current genetic PGD testing is approximately 99%. This truly amazing kind of science is made possible by the combined efforts of multiple talented and dedicated individuals in the embryology and molecular genetics laboratories.
PGD has been accomplished for several hundred different genetic diseases. Worldwide, over 6,000 PGD cycles for genetic disease identification have been performed. The most common indications for PGD testing include; cystic fibrosis, beta-thalassemia, Huntington disease, myotonic dystrophy, spinal muscular atrophy, and fragile X syndrome. Here at GIVF, we have successfully performed several hundred PGD cycles for genetic disease prevention that have resulted in many healthy children being born free of the genetic disease.
Couples interested in PGD for genetic disease prevention first meet with our genetics specialists to review their medical history and begin the DNA analysis of the couple's family members. They also meet with our Reproductive Endocrinologists (infertility specialists) prior to initiation of an IVF cycle. Both groups of specialists then work together as the IVF cycle starts in order to provide comprehensive and continuous care throughout the PGD process and beyond. If you are interested in learning more about our PDG program, please call 703.698.7355 or click here.
Dr. Stern is the Director of Reproductive Genetics and the Fetal Diagnostic Center at GIVF. To learn more about Genetic Services at GIVF, click here.
25th Annual Baby Reunion
On Saturday, May 7, 2011, GIVF will host the 25th Annual Baby Reunion. The reunion is always a heartwarming event for our many patients, their families, and our dedicated staff. It is a joyous occasion that patients and staff alike look forward to each year. In fact, the very first baby born as a result of GIVF will be in attendance this year!
Helping Children Worldwide
The Genetics & IVF Institute is a proud supporter of Helping Children Worldwide a local non-profit in Herndon, VA. Helping Children Worldwide is 501 (c) 3 non-profit that works to transform the lives of impoverished children through partnerships and programs of excellence. Helping Children Worldwide supports nearly 250 children in Sierra Leone through the Child Rescue Centre, 10,000 patients a year at Mercy Hospital in Sierra Leone, and one non-profit center Connections for Hope, in Herndon, VA. Click here to watch a video about Connection for Hope.
Connections For Hope opened on March 15, 2010 and successfully operates as a partnership of non-profits and county agencies working collaboratively under one roof to provide individuals and families in need with access to an integrated array of services. Helping Children Worldwide underwrites two-thirds of the cost to run the center, including underwriting a portion of the rent for each of the organizations. This makes it possible for the partners to be involved and provides the shared space that all organizations use in serving their clients. It is a center that was developed by the community, for the community, in the community. The money saved by the organizations because of lower rental costs can be invested in improved and additional services. There is a growing need in our community, 12.5% of Fairfax County residents have incomes under 200% of the poverty level ($44,100 per year for a family of four) and 25% of the Fairfax County Public Schools children are on the Free and Reduced Lunch Program. Connections for Hope was developed in response to these growing needs and continues to build partnerships to create a stronger community.
Connections for Hope is a hospitable center where people are truly working together for the betterment of our community, a place clients feel comfortable coming for services. Services available include medical care, language training, homework assistance, legal counseling, homelessness prevention, and mental health services. The Jeanie Schmidt Free Clinic (JSFC) is a free medical clinic offering care for any child in Fairfax County that qualifies as living below 200% of the poverty level, and provides healthcare for adults with hypertension and diabetes. Before the JSFC moved to Connections for Hope they were treating patients behind curtains on gurneys. Since JSFC opened at Connections for Hope they treat patients in six exam rooms, just like you would find at your doctor’s office, and have seen nearly 1,800 patients in over 7,000 appointments, with less than 10 full time employees and over 300 volunteers. Once patients are in the door at JSFC they have access to a whole network of physicians! The JSFC and the other partner organizations work together to provide clients with multiple services in one location.
Connections for Hope is located at 13525 Dulles Technology Drive, Suite 103 in Herndon, VA. For more information, please contact Sarah Newman, Director at 703-793-9521 or email@example.com.
Infertility Can Cause Significant Male Sexual Problems
by Ash Kshirsagar, MD
An estimated two to six million US couples have infertility issues. The medical community has recognized that infertility causes significant psychological stress on couples that can manifest as anxiety, depression, and even sexual dysfunction. A significant challenge to infertile couples is that infertility is not fully acknowledged as a medical problem by some in the lay public as well as certain insurance companies, despite a US Supreme Court opinion which considers some infertility as a disease. Unfortunately, the lack of validation of infertility as a medical struggle increases the stress on couples. Furthermore, couples often assume the burden of infertility in isolation. With such a large number of couples facing infertility in the US, the Centers for Disease Control (CDC) is now looking at infertility as a public health issue.
One aspect of infertility that is often overlooked is the impact on male sexual performance that men experience when a couple is trying to conceive. Some men will silently struggle with a form of performance anxiety and non-physiologic erectile dysfunction that occurs when men perceive a change in sex from something more recreational or an expression of love to a more goal driven activity focused on procreation. In some men, the self-imposed expectations that occur when sex changes from something previously more casual to a goal-driven activity can decrease their ability to relax. This can directly inhibit their ability to perform and can cause erectile dysfunction.
As the period of infertility increases, the level of stress can be compounding. Additionally, as some couples may not have much physical intimacy prior to attempting conception, some men are placed in a situation they have not dealt with in the past. Men, especially if they are the partner who has the infertility issue (like a low sperm count), may feel guilt or blame for the situation. This can really strike a blow to the sense of self because of the male's traditional or cultural role as the partner who provides for the family unit.
This stress can change the act of sex in some men’s psyche from something pleasurable to something stressful, with the sex act being viewed, at times as a chore. Although it may come as a surprise, some men will try to avoid sex because of how incredibly challenging it can be for them to perform in these situations. Men have related to their physicians that their female partners misinterpret their erectile dysfunction as a sign that the man is no longer in love, interested, or physically attracted to the female partner. They carry this guilt with them to the bedroom, which further adds to their stress and inability to perform.
What are the solutions? Often, men will ask their physicians for medications like Viagra™. It is unclear if using such medications is the answer. Erectile issues in this group of men usually do not result from an underlying physiologic medical condition that medications like Viagra™ are intended to treat. Like any medication, there are some uncommon but potentially serious medical side effects from medications like Viagra™. In addition, there is also the risk of psychological dependence upon these medications to such an extent that even after the fertility issues have resolved the men will feel they need these medications in order to perform. If men choose to rely on medications, then they must be aware of and prepared to take responsibility for the risks.
Other measures for addressing a male's performance issues may require a greater time investment but also may have better, longer lasting results. One of these measures includes seeking counseling from a licensed psychiatrist or clinical psychologist who specializes in sexual dysfunction. This is usually more effective when both partners undergo evaluation together, but can still be effective if only the male partner attends. Other options that may help include:
- Speaking to the female partner about the situation. Although some men may be embarrassed to do so, it may relieve the unspoken tension and clear misconceptions. The female partner may be relieved to know she is still desirable to the man and that performance issues do not imply a loss of his love or attraction.
- Trying to ensure that intercourse for procreative purposes isn’t the only physical or emotional intimacy between the couple. This can take the stress off the times when intercourse is for procreative purposes; otherwise some men may relate any intimacy to their risk of failure or inability to perform.
- Ensuring that the inability to conceive doesn’t define you as a couple or become all-consuming. Although this may be challenging, make time to do the enjoyable things that you do as a couple without the thought of having to go home and try to make a baby by night’s end. It is important to think of yourselves as a couple first, not as an infertile couple.
- Speaking to their physician: simply getting the issue, “off of their chest,” and into the open can sometimes bring a sense of relief for men. Also, the validation that they are not suffering from a physiologic abnormality can help alleviate stress.
- Confiding in a male friend. Often men think they are the only one suffering from such issues, but are often surprised and relieved to hear that the situation is more common than they thought.
- Remembering that it is a misconception to think that being able to perform is something that can be turned on or off like a switch that works 100% of the time. There are many factors that can influence the ability to perform: lack of sleep, both non-marital and marital stress, level of stimulation, and even some medical conditions/medicines. Even a professional athlete has an occasional bad day: the goal is just not to fall into a “pitcher’s slump.”
One resource men may find helpful is the book, “What He Can Expect When She’s Not Expecting,” by Marc Sedaka. You can learn more about male infertility with Dr. Kshirsagar at www.washingtonmalefertility.com or www.nationalvasectomyreversal.com.
Dr. Kshirsagar is a regular contributor to GIVF eNews and is available to see male infertility patients, click here to schedule an appointment.
The Genetics & IVF Institute (GIVF) regularly publishes an informative newsletter featuring the latest infertility news and developments. The newsletter is sent electronically via email. To subscribe, click here.