Gender Selection- Family
Balancing -Seattle, Bellevue Gender Selection Program
Many couples wish to experience the
joy of having a boy and a girl. They might also desire
a particular gender because they have genetic diseases
in their family that are sex-linked
(carried on the sex chromosome). Sex linked
diseases can only be transmitted to a child of a particular
gender and include, hemophilia, Duchene’s, muscular
dystrophy, Lesch Nyhan syndrome, and others. Our Washington fertility clinic offers PGD to screen for genetic diseases and gender selection.
There are several gender selection methods available
to select sperm that will produce either a boy or
a girl, however; these gender selection methods are only marginally
successful. Our clinic has chosen to offer preimplantation
genetic diagnosis (PGD), as it is extremely reliable
in selecting an embryo of known gender facilitating family balancing.
In an IVF
cycle, an embryo biopsy is performed on the third
day (eight cell stage). The biopsy does not damage
the embryo or hinder further development.
Using preimplantation genetic diagnosis for gender selection, the genetic material is amplified using the polymerase chain reaction (PCR), which makes several identical copies of the DNA. Fluorescent probes that are specific to the X and Y chromosomes are then employed and XX (female) and XY (male) embryos are readily identifiable. Testing for some chromosome abnormalities, such as Down’s Syndrome, is available as a part of this process at no extra charge.
On the fifth day the selected embryos (now blastocysts) are placed into the uterine cavity resulting in a very high rate of success with conception of a fetus of the selected gender.
PGD is the only
means to virtually “guarantee” successful gender selection. Some procedures, such as Microsort,
offer limited success with X, Y sperm sorting techniques
but they are experimental and not offered by our clinic.
Why Not MicroSort?
A number of recent advances in the field of Assisted Reproductive Technologies (ART) have afforded couples and prospective parents the ability for family balancing, sex selection, and the avoidance of X-linked genetic diseases in offspring.
One particular method, flow cytometric sorting of human sperm (commonly referred to as MicroSort), has been touted as a reliable tool for the separation of X- and Y-bearing sperm (Karabinus 2009) and has consequently been used by couples considering family balancing. The principle group offering this service (MicroSort Division of the Genetics and IVF Institute in Fairfax, VA) has recently published data suggesting a reasonable ART success rate regarding the technology (Karabinus 2009).
However, the technology is not readily accepted in the ART community as main-stream and not commonly applied to ART treatments. Indeed, the program offered by MicroSort and other groups across the country is still in Clinical Trials, as evidenced by their update in 2009 (Karabinus 2009).
Our clinic has a steadfast commitment to offering our patients the most reliable, safe, and efficacious procedures involved in their reproductive treatments. Given the fact that MicroSort technology is still in clinical trials, patients considering this treatment must be conscientious and critical of its potential merits and disadvantages. To this end, we have performed a detailed review of the scientific literature regarding the efficacy of MicroSort in ART and discuss our findings below.
EFFECTIVENESS OF SPERM-SORTING FOR X- AND Y-BEARING SPERM
The MicroSort division at Fairfax has recently published data suggesting successful sorting of X-bearing sperm (those capable of producing a female offspring) of 90% (Karabinus 2009). However, the efficiency of the technology to successfully sort Y-bearing sperm (those capable of producing a male offspring) falls to 70% (Karabinus 2009).
An independent study of the technology suggested the successful sorting of X-bearing sperm may be as low as 80%, while the successful sorting of Y-bearing sperm may be as low as 60% (Vidal et al., 1998). Other reviewers have noted that according to all published data, the different sex-chromosome separation techniques have been shown to not be very effective (Michelmann et al., 2000). Furthermore, that the only method showing significant enrichment is the flow cytometry of sperm for X-selection (Michelmann et al., 2000).
Therefore, the literature indicates only a 10-20 percent increase in the chances of a male offspring versus no treatment at all. The chances for a female offspring are higher by 10 to 20% percent.
Due to these modest rates of purification, here at the Washington Center for Reproductive Medicine, our approach to gender selection has been to offer IVF in conjunction with pre-implantation genetic diagnosis (PGD).
93% of couples completing IVF/PGD cycles at our center have been able to transfer one or more embryos of the sex they initially desired. In light of these rates of success, we have discouraged our patients from pursuing MicroSort techniques due to the additional expense and the possibility of deleterious effects of MicroSort on embryo development.
EFFECTS OF MICROSORT ON EMBRYO DEVELOPMENT
In considering this technology for ART, one must also be conscientious of the effects of the MicroSort technique on sperm function and the downstream effects on embryos produced from sperm sorted with flow cytometry.
One of the principle reasons why MicroSort is still in clinical trials is due to the lack of data reported on human embryos which have been generated from MicroSort treated sperm.
However, a great deal of literature has emerged regarding animal data. In three recent studies, sex-sorting of spermatozoa using flow-cytometry (identical to MicroSort technology) have produced significantly negative effects on early embryo development (Palma et al., 2008; Lu et al., 1999); and McNutt et al., 1996). In particular, the suitability of sperm sorted using flow-cytometry was lower than non-sexed sperm and the ultrastructural studies of blastocyst-staged embryos produced with flow-cytometrically sex-sorted spermatozoa possessed deviations in many key developmental aspects (Palma et al., 2008).
Due to the lack of human data regarding the effects of MicroSort technology on sperm DNA integrity, physiological and developmental aspects of developing embryos, we have determined the most responsible method for pursuing gender selection is to offer our patients IVF in conjunction with PGD.
Indeed, the IVF success rates emerging from the Clinical Trial published by the MicroSort facility in Fairfax, VA were far below our clinic’s success rates for PGD cases in 2008. The IVF clinical pregnancy rate for MicroSort’s clinical trial was only 32%. In stark contrast, the clinical pregnancy rate of our IVF/PGD cycles in 2009 was 76%. The difference in rates may well be attributed to the deleterious effects of flow cytometry on the developmental competence of the subsequent embryos. Thus, we have concluded that the more proven technologies, such as PGD in conjunction with IVF, may be a better option at this time for patients pursuing family balancing.
COST OF MICROSORT
In these tough economic times, it is important for patients to choose the most cost-effective approach to attain their gender selection goals. Given the effect of MicroSort on sperm function, most of the patients utilizing the technique must also be treated with IVF in conjunction with ICSI (intracytoplasmic sperm injection), where a single sperm is selected and injected into each oocyte. If not for the MicroSort application, the ICSI procedure would be unnecessary for many of these patients given they have proven fertility. Thus, patients choosing this approach must pay for an IVF cycle, ICSI, as well as the MicroSort technique which could add thousands of dollars to their treatment plan.
SUMMARY
- MicroSort for gender selection is still in clinical trials.
- IVF/PGD without MicroSort has provided 93% of the couples treated at the Washington Center for Reproductive Medicine with the sex of offspring desired.
- Gender selection success rates with IVF/PGD at the Washington Center for Reproductive medicine are much higher than those published by MicroSort.
- MicroSort sperm have been reported to negatively effect embryo development in animal studies.
- MicroSort adds thousands of dollars to the cost of ART treatment.
REFERENCES
- Karabinus DS. Flow cytometric sorting of human sperm: MicroSort clinical trial update. Theriogenology 2009. 71(1): p 74-9.
- Lu KJ; Cran DG; Seidel GE Jr. In vitro fertilization with flow-cytometrically-sorted bovine sperm. Theriogenology 1999. 52(8): p 1393-405.
- McNutt TL; Johnson LA. Flow cytometric sorting of sperm: influence on fertilization and embryo/fetal development in the rabbit. Mol Reprod Dev. 1996. 43(2): p 261-7.
- Michelmann HW; Gratz G; Hinney B. X-Y sperm selection: fact or fiction? Hum Reprod Genet Ethics. 2000. 6(2): p 32-8.
- Palma GA; Olivier NS; Neumuller CH; Sinowatz F. Effects of sex-sorted spermatozoa on the efficiency of in vitro fertilization and ultrastructure of in vitro produced bovine blastocysts. Anat Histol Embryol. 2008. 37(1): p 67-73.
- Vidal F; Fugger EF; Blanco J; Keyvanfar K; Catala V; Norton M; Hazelrigg WB; Black SH; Levinson G; Egozcue J; Schulman JD. Efficiency of MicroSort flow cytometry for producing sperm populations enriched in X- or Y- chromosome haplotypes: a blind trial assessed by double and triple colour fluorescent in-situ hybridization. Hum Reprod. 1998. 13(2):
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