CHR Update November 2001

Preimplantation Genetic Diagnosis (PGD) for
Repeated Pregnancy Loss

For couples affected by repeated (or “habitual”) pregnancy loss, the experience of loosing pregnancies can be devastating. Fortunately, PGD has now given us a new tool to improve outcome chances for such couples.

WHAT IS REPEATED (“HABITUAL”) PREGNANCY LOSS? Under the classical text book definition, a woman is considered a repeat (“habitual”) aborter only after she has experienced three consecutive pregnancy losses in the first trimester or two such losses, with one having occurred in the second trimester. The very large majority of all pregnancy losses, however, occur early and, therefore, the definition of three losses applies to most patients. Indeed, some insurance companies will not approve payments for any diagnostic tests and/or treatments
under this diagnostic code, unless a patient has experienced three consecutive losses. In some patients, especially older patients, it may, however, not make sense to wait for three losses before a diagnostic work up is instituted. At CHR we, therefore, individualize our recommendation when to start evaluating a couple with repeated pregnancy loss.

WHAT CAUSES REPEATED PREGNANCY LOSS?
Pregnancy loss is very common in humans. Approximately 15 percent of all pregnancies are lost spontaneously and this percentage increases with female age. Approximately 85 percent of this loss is due to chromosomal abnormalities which in over 95 percent of cases are the consequence of egg abnormalities. Since such egg abnormalities increase as a woman ages, chromosomal abnormalities in embryos increase and,
with it, the rate of pregnancy loss.

There are many other reasons for pregnancy loss, with immunological causes probably representing the second most frequent underlying process, though at only a small fraction of the genetically induced losses.
Genetically induced losses occur, however, in most cases (though there are exceptions) at random, while losses due to underlying medical conditions usually occur at a more persistent pattern. In practical terms that means that, the more consecutive losses a couple has experienced, the smaller the chance of a genetic cause and
the larger the probability of a medical etiology, such as, for example, abnormal immune function or undiagnosed diabetes mellitus.

PGD TO REDUCE PREGNANCY LOSS

If the possibility of a medical cause for repeated pregnancy loss has been ruled
out, genetic loss becomes an extremely likely explanation. Indeed, some studies have demonstrated that there are some couples who produce, even though their own chromosomes may be normal, a much higher prevalence of genetically abnormal embryos than their age mandates.

Such couples can only be identified by PGD. In other words, only the genetic investigation of their embryos can lead to these couples’ correct diagnosis. Once diagnosed, PGD then offers the additional advantage of allowing us to place only genetically normal embryos into the female’s uterus.

A number of studies have demonstrated that, using PGF for this purpose, reduces
subsequent miscarriage rates significantly.

PGD AT CHR
CHR has been offering PGD services for over 10 years. For over two years, we perform all aneuploidy testing (i.e. the testing for chromosomal abnormalities) in house. This means that, in contrast to most other IVF programs, we don’t ship either embryos or blastomers (i.e. individual cells from embryos) to other laboratories for chromosomal analysis.
We have, in regular intervals, checked the pregnancy rates of our program after embryo biopsy for PGD and have found absolutely no differences to regular IVF cycles which have not undergone the procedure. We are, therefore, confident that PGD, for diagnostic as well as therapeutic reasons, represents a very valuable and cost-effective option for couples with unexplained repeated (“habitual”) pregnancy loss.

A UNIQUE PRESCREENED SELECTION OF EGG DONORS

By the time a couple reaches the point of considering egg donation, they usually either have experienced considerable time in fertility treatment and/or are of quite advanced age. This then, of course, means that the selection process for a fitting egg donor assumes

considerable urgency. Unfortunately, this urgency cannot be met by most IVF centers because they, mostly for cost reasons, do not maintain prescreened donor pools. It is, therefore, not uncommon that patients, by the time they reach CHR, have been on egg donor waiting lists for months, at times for periods exceeding a year.

This problem is especially acute for non-Caucasian patients. We just a few days ago saw an Asian patient from New Jersey who has been on a number of local waiting lists for approximately one year and, finally, came to CHR in New York City, because, after all of this time, she was still only number two or three on the Asian waiting list. We matched her, practically, within 48 hours.

There are a number of reasons why CHR can match almost everybody, and of any ethnicity, in almost all cases, within days:
(1) CHR has probably the largest pre-screened donor pool of any IVF center

in the country. Our pool, at any given point, includes over 150 women who, after extensive review, have been found qualified as egg donors.

(2) CHR receives, on the average, approximately 50 egg donor applications per week. Amongst those, approximately 10% of applicants pass initial scrutiny and are interviewed. Amongst those reaching interviews, maybe, one to two will be added to the donor pool after two rounds of lengthy face to face meetings with staff and physicians, respectively.

(3) CHR selects donors for quality and diversity. This means that, when selecting candidates for our donor pool, we are not only uncompromising about the overall quality of our donors but, in addition, also select donors of greatly varying ethnicities. For that reason

(4) CHR has donor of almost all ethnicities and religions, with particularly strong representation of various Asian ethnicities . For example, we believe to be the only East Coast program with a large pool of Chinese donors and our Chinese egg donation program has become so large that it now is managed by a Mandarin- and Cantonese- speaking Chinese coordinator, Helena, who can be reached directly by calling 917-733 7672. Other rare ethnicities and religions, represented in our current donor pool are Asian-Indians (Muslim as well as Hindu), Japanese, Vietnamese, Filipino, Brazilian, Greek, Turkish, Icelandic, West-Indian, African, as well as Muslims, Jewish donors. In addition, we, of course, also have excellent donors of more widely available ethnicities and nationalities, such as English, Irish, Scott, Welsh, Italian, German, Dutch, French, Swedish, Native American, African-American, Polish, Czech, Russian, Swiss, Hungarian, Slovakian, Puerto Rican, Columbian, Guyanese, Trinidadian and many more.

(5) CHR also has donors available for uncommon recipient requests. For example,
while a large majority of egg donors and their recipients prefer that the egg donation process be anonymous, some recipients insist on an “open” donation. We usually have donors available who are willing to participate in “open” donations.

In short, almost any potential egg donation recipient at CHR will be matched with a well fitting donor within a very short time period. There is simply no reason for patients to delay their conception by placing their names on endless
egg donor waiting lists. Click here if you wish to want more information on our Egg Donor Program.

Norbert Gleicher, MD, leads CHR’s clinical and research efforts as Medical Director and Chief Scientist. A world-renowned reproductive endocrinologist, Dr. Gleicher has published hundreds of peer-reviewed papers and lectured globally while keeping an active clinical career focused on ovarian aging, immunological issues and other difficult cases of infertility.