Gender Selection- Keith L Blauer, MD
Gender selection is becoming more common for many couples. Many of us know someone who would desperately like to have a girl, or a boy. Perhaps a couple has several children of one gender already and would like to have another child --- but would only consider doing so if the 50/50 odds could be shifted in favor of the other gender. Or, perhaps a couple is seeking infertility treatment, already has one child, and would prefer to employ gender selection for the next child. Yet another couple may want to use the technology to avoid passing one of the more than 500 gender-linked genetic diseases to their child. 
I received emails and telephone calls from couples around the country who were interested in gender selection technology while I was the Director of the MicroSort program at Genetics & IVF Institute in Virginia.
One call was from a couple who lived in Salt Lake City. Susan (not her actual name), the wife, a 24 year old, was interested in sex selection technology. She had researched the options and was aware that MicroSort and preimplantation genetic diagnosis were the only scientifically verifiable methods for increasing the odds of a particular sex.
Gender selection can dramatically reduce the chances of transmitting a sex linked disease to a child, especially when PGD is used. Susan was a known carrier of a gene for retinitis pigmentosa (RP) and knew that if she and her husband had a boy that their son would have a 50% chance of having the disease. Retinitis pigmentosa is a progressive degeneration of the retina (part of the eye). It affects night and peripheral vision. The hallmark of the disease is the presence of dark pigmented spots on the retina. The condition usually eventually leads to blindness.
Gender selection could greatly decrease the chance of transmitting the disease to her child. Susan had male family members that were affected with RP. Signs and symptoms may appear in childhood but severe visual problems usually do not develop until early adulthood.
We communicated about gender selection in her case several times by email and by phone discussing the options including the use of MicroSort sorting technology or preimplantation genetic diagnosis for gender selection. After numerous discussions, she and her husband chose to employ Microsort and had her husband’s sperm sorted at the Laguna Hills MicroSort lab. The sorted sample had a purity of 92% for X (female) bearing sperm.
She then underwent in-vitro fertilization at Reproductive Care Center with Dr. James S. Heiner using the sorted sperm to fertilize the eggs. Two embryos were transferred into the uterus and she subsequently became pregnant with twin girls. She and her husband were very grateful that the technology was available to help them have healthy baby girls.
Men determine the gender of their offspring. When a sperm with a Y chromosome fertilizes an egg, it makes a boy. When an X chromosome bearing sperm fertilizes, it makes a girl. Any given sperm sample contains an even (50/50) amount of X (female) and Y (male) bearing sperm.
Gender selection would be used frequently if success could be guaranteed. Couples have sought to influence the sex of their children for hundreds of years. In ancient Greece, men believed that lying on their right side during intercourse increased the likelihood of a male child. A Chinese birth calendar buried over 700 years ago in a tomb outside Beijing is said to predict sex by when conception occurred. In 18th century France, men would tie off or remove one of their testicles to ‘guarantee’ a boy.
Gender selection today in America has employed several methods such as timing of intercourse in relation to ovulation, length of abstinence, sexual positions, or spinning live sperm in an albumin gradient. According to the American Society of Reproductive Medicine, none of these methods has been shown to be effective. Only MicroSort technology and PGD have documented effectiveness in sex selection.
Gender selection technology has been investigated by The Genetics & IVF Institute (GIVF) in Fairfax, Virginia since the early 1990s. In 2001, the FDA approved an ongoing clinical trial for GIVF's proprietary preconception gender selection process, called MicroSort®. As the only scientifically verifiable method of pre-conception gender selection, MicroSort is now likely to be discussed as couples consider sex selection in future pregnancies. Especially helpful for families with x-linked diseases, MicroSort significantly lowers the risk of having an affected child from approximately 25% to 5%.
Gender selection employing MicroSort uses a machine called a flow cytometer to sort sperm such that the sorted sperm population is enriched in either X (female) or Y (male) bearing sperm depending on the desired gender. The separation of male and female sperm is based on the measurable difference in the quantity of genetic material (DNA) they contain. The sperm absorbs a dye, which attaches temporarily to the DNA, or genetic material, inside the individual sperm. When exposed to laser light, the dye fluoresces. Since the X chromosome is larger than the Y, there is more DNA for the dye to attach to and, consequently, the sperm with the X chromosomes will fluoresce more brightly than those with Y chromosomes. The flow cytometer is able to pick up these differences in brightness and separate the sperm as they move through the machine one at a time.
Based on abstract publications, currently, MicroSort gender selection sperm sorting technology improves the chance of a female pregnancy to 91% percent after sorting. For a male, MicroSort improves the chance to 76% percent. MicroSort has accomplished more than 700 pregnancies and 600 births. Based on the data reviewed so far, the likelihood of having a normal, healthy baby does not appear any different from that of the general population. Since MicroSort currently is in a clinical trial, patients must be fully informed of the potential risks and benefits.
In order to qualify for the clinical trial, which is expected to continue for several more years, couples must currently be in one of two categories.
- A couple with a history of one of the more than 500 identified X-linked disease, where the woman is a known carrier, may qualify for reduced-cost treatment with MicroSort gender selection technology. Examples of such disorders include hemophilia and Duchenne muscular dystrophy.
- Qualifying couples can choose to use MicroSort for “family balancing”. Family balancing couples must: be married; the wife must be between ages 18 and 39; they must have at least one child, and they must be employing gender selection for the less represented sex of children in their family.
Once the sperm has been sorted, it can be used with various assisted reproductive techniques to achieve a pregnancy. The most common method uses the sorted sperm with intrauterine insemination (IUI). In such a procedure, the woman is monitored carefully to establish the time of ovulation. Some of this monitoring can occur with local collaborators such as the Reproductive Care Center in Utah and/or the use of ovulation predictor kits, which can be used at home. IUI is performed very close to the time of ovulation. On the day of ovulation the husband produces a semen sample, the sperm are sorted for the desired sex using MicroSort technology, and the insemination with the sorted sperm occurs later that same day.
At the current time, couples desiring gender selection must go to one of the MicroSort Laboratory sites in Fairfax, Virginia or Laguna Hills, California (in conjunction with Huntington Reproductive Center) to have their IUI procedures performed with fresh specimens. IUI is the least costly and least invasive method of treatment. Pregnancy rates per cycle are about the same as achieved through normal intercourse (15-20%).
For patients who need additional assistance to achieve pregnancy, or who seek to raise the odds of achieving a successful pregnancy, sorted sperm can be used with IVF. Fresh sperm can be used, or sperm can be sent frozen, then sorted and returned to a local IVF centers such as the Reproductive Care Center, allowing the couple to have IVF close to home.
Physicians offering gender selection in conjunction with IVF must be collaborators with the MicroSort clinical trial in order to offer this technology. Embryos from the IVF cycle are more likely to be of the preferred sex when sorted sperm is used. A list of national and international collaborators can be viewed at the MicroSort Web site (www.MicroSort.com). Several couples from Utah with X-linked disorders have achieved pregnancy at the Reproductive Care Center using MicroSort sorted sperm in conjunction with IVF.
Gender selection rates approach 100% with the use of PGD and many couples may decide that they want to use this technology. To accomplish this, embryo testing (Preimplantation Genetic Diagnosis or PGD) in conjunction with IVF can be performed and only embryos of the preferred gender will be placed in the uterus. In addition, sperm sorted using the MicroSort can be used with an IVF cycle to result in more embryos of the desired gender.
In PGD, one to two cells are removed from these early embryos, and then DNA based genetics analysis is performed in highly-specialized regional laboratories. Upon completion of the analysis, which takes about 24 hours, couples can select which embryos they will use. If pregnancy results, there is almost a 100% chance it will be of the desired gender. This method is particularly helpful for couples where the risk of having a male child with an X-linked genetic disease is significant.
One concern with PGD is the issue of what to do with embryos that are not chosen for uterine transfer. This same issue arises every day at in vitro fertilization (IVF) clinics around the world, where millions of people over the past 25 years have used IVF technology to have children who otherwise had no hope. The current options for couples who have extra embryos after completing an IVF cycle include: 1) cryopreserve the embryos for possible future use by the same couple, 2) donate the embryos to other infertile couples who are unable to produce their own embryos, 3) donate the embryos to research, 4) discard the embryos.
Use of either of these gender selection technologies by normal couples who are not at obvious risk for genetic disease transmission is of great interest to many of patients. Healthy couples who only have children of one sex may desire to use this technology to influence (MicroSort) or even determine (PGD) the gender of their next offspring.
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