Family balancing

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THE ROLE OF GENDER SELECTION: THE PRO’S & CON’S

Geoffrey Sher

Couples have for centuries sought to influence the gender of their offspring. More than seven centuries ago the ancient Chinese developed a birth calendar said to be able to predict gender on the basis of when conception occurred. Later, the ancient Greeks suggested that by lying on her right side during intercourse, a woman could improve the likelihood of having a male child. And 300 years ago, the French suggested that placing a ligature around the right testicle would improve the chance of having a male child.

More recently in the U.S., methods such as timing intercourse, assuming different positions during sex, and (relatively recently) employing rapid sperm centrifugation in an attempt to separate male chromosome-bearing sperm from female sperm prior to artificial insemination were proposed. The fact is that none of these (as well as many other) such anecdotal assertions have been shown to have any real validity.

Currently, in spite of several well described medical approaches, the indisputable fact has emerged that it is only by way of IVF that reliable sex selection can be achieved. This allows for embryos to be screened for gender through preimplantation genetic diagnosis prior to transferring the embryo(s) of the desired gender to the uterus.

Nevertheless, it is an inescapable reality that the very idea of medical sex selection challenges moral and ethical beliefs at their very foundation. Many hold that the growing popularity of gender selection solely for the convenience of altering a family’s gender balance represents an unwanted example of how assisted reproductive technology is subject to abuse…and thus it should be outlawed. They also see it as an example of a disturbing trend towards “designer babies” where genetic engineering could be used to manipulate the intellect, body configuration, build, height, and the talents of future offspring. This assertion is commonly followed by the tantalizing question as to where all this would end and whether we as a society “would really want to live in such a world.”

There is, however, one clear exception to the apparent across-the-board opposition to sex selection that is well worthy of mention. This applies in cases where sex selection is used to avoid the occurrence of a serious medical disorder that selectively affects one gender or the other (e.g., Hemophilia, a life threatening bleeding disorder that selectively affects male offspring).

EVALUATING CURRENTLY USED METHODS FOR SEX SELECTION

SPERM GRADIENT METODOLOGY (discredited because of a lack of reliability)

This is one of the simplest methods that still (unfortunately) remains in widespread use. Here sperm is rapidly spun down (centrifuged) in the hope of separating the male sperm (those with Y-chromosomes) from the female sperm (those with X-chromosomes). It relies on the assumption that the X chromosome makes sperm heavier, allowing for separation of male from female chromosome-bearing sperm. Though this method is often touted as a low cost method for sex selection, the truth is that it simply does not work!

LOW CYTOMETRIC TESTING BY THE MICROSORT METHOD (discredited because of a lack of reliability)

This method which is now somewhat discredited by the FDA  employedthe use of a fluorescent dye that adheres to genetic material within the sperm. It was based on the premise that because X-bearing sperm contain more genetic material, these sperm were supposed to pick up more dye than Y-bearing sperm. Thereupon, X and Y bearing sperm are then separated into two groups and used for intrauterine insemination (IUI) or IVF. This method was touted as yielding a 60% to 70% accuracy rate with IUI. This has not been adequately confirmed and in my personal experience its reliability in the IVF setting has been questionable to say the least. The Microsort technique is to my knowledge not presently being offered in the United States.

IVF using PREIMPLANTATION GENETIC DIAGNOSIS (PGD)

Preimplantation Genetic Diagnosis (PGD) involves the removal of one or more cells from an embryo, for chromosomal or genetic analysis.  The most widely used and he most reliable PGD method for gender selection is fluorescence in-situ-hybridization (FISH). However, this technique does not identify all 23 pairs of chromosomes in the embryo’s cells. At best it can well identify 12. Thus, while FISH provides an excellent method for gender selection and for identification of structural chromosomal aberrations, it is not a reliable method for diagnosing embryo aneuploidy (“competency”).  Conversely, another PGD method, next generation gene sequencing (NGS) which does assess all the embryo’s chromosomes can be used for both detecting all the embryo’s chromosomes and thus can determine embryo “competency” reliably. It also reliably identifies gender. However, while NGS is very bit as reliable as FISH for gender selection, FISH can be done in fresh cycles (i.e. the ET is done in the same cycle as that in which the ER is done), while NGS requires time for testing that requires Staggered IVF (St-IVF) in which the embryos are biopsied on day 3 or day 5-6 (post-fertilization) and  the blastocysts are ultrarapidly frozen (vitrified) and allowed to proceed in culture to blastocysts whereupon they are ultra-rapidly frozen (vitrified) and are then held for transfer in a subsequent cycle. 

Upon completion of FISH, which takes about 24-36 hours, the couple can select which embryo(s) they will transfer to the uterus. If pregnancy results, there is almost a 100% chance it will result in the desired gender. If NGS is used, the degree of accuracy in diagnosing gender, is as reliable as is FISH but in addition, NGS provides information on the entire karyotype (all 23 pairs of chromosomes) which is extremely beneficial because it assesses embryo “competency, while FISH does not.

A PERSONAL OPINION:

Sex selection done purely for  family balancing is somewhat  controversial, raising concern that if  widely accessible and freely available, such practice could distort the natural sex ratio, leading to a population gender imbalance. However, for this to happen, there would have to be a significant population preference for sex selection. In reality, the contrary seems to apply, since studies conducted in western societies discount these concerns. In fact, the relatively high cost of IVF with the added cost of gender selection in the United States makes it unlikely that the demand would ever become large enough to impact overall population gender balance. In addition, several studies done in Western countries have shown that the majority of people do not seem to be concerned about the gender of their offspring, and that with a few notable exceptions, gender preference does not appear to be slanted in the direction of either male or female. Thus, from a practical standpoint, such concerns are overstated.

Given that in the United States most couples do not care about the gender of their offspring, and only a minority are interested in selecting the sex of their children there is currently  no risk that IVF sex-selection will impact the population gender balance. Thus, in  my opinion by and large,  freedom of choice should prevail and a service for sex selection should be freely available

 So, in my personal practice, I absolutely do offer gender selection in the following circumstances.

• Medical Indications for Gender Selection:
  • For cases associated with
    • sex-linked genetic disorders or,
    • serious genetic disorders that are more likely to occur in one gender or the other.
  • Non-Medical Family balancing
    • For couples who have at least one child of the opposite gender to that which they choose for their IVF embryo transfer and,
    • For those women who do not have any children at all but prefer to have a child of one or the other gender.