Introduction
Within mammalian species, pregnancy is immunologically privileged. By
rules of this concept, a conceptus transferred into a host uterus can be
carried uneventfully to viability with a parturition time determined by the
genetics of the oocyte donor. 1,2 Clinical exploitation of this principle, long
established in laboratory animals and livestock breeding, produced the first,
reports of viable pregnancies to infertile women in 1983 and first births in
1984.3-5 During 1994, in the United States alone, more than 929 pregnancies
producing viable births from donated oocytes and embryos were cele-
brated. 6 With this number increasing steadily, oocyte and embryo donation
occupies a highly significant role in the practice of reproductive medicine.
1
2 John E. Buster
alone.! By 1980 more than 40,000 calves had been birthed following embryo
transfer with no apparent excess of fetal anomalies.!
FiGURE 1.1. Blastocyst recovered by uterine lavage and transferred into an infertile
recipient woman synchronized to the cycle of the donor. In 1983 this blastocyst
produced the first in vivo fertilized donor embryo pregnancy in history.5 l8 Reprinted
o
through 1986. The uterine catheter used in these studies is shown in Figure
1.2. A total of 35 ova were recovered from 84 spontaneous cycles. Of the
35 ova recovered, 8 were blastocysts, and of the 8 blastocysts transferred,
4 produced clinical pregnancies in recipients. 19 A very similar experience
was reported from the University of Pavia in Milan by Formigli et al.2 3- 25
Work with uterine lavage for transfer of donor embryos was discontinued
in 1987, not because of lack of promise, but because the specter of HIV
infection posed an unacceptable risk for donors. It also became clear that
lavage was a relatively inefficient method of embryo acquisition when used
with spontaneous cycles. 19 Methods to enhance its efficiency are under in-
vestigation again because of its application to preimplantation diagnosis. 26 ,27
Recent Developments
Over the decade that followed these initial reports, donor oocytes and em-
bryos became established, effective therapy for several forms of intractable
infertility. The technique has seen increasing use because of technical im-
provements in in vitro fertilization and because clinicians have applied it to
an increasing number of clinical problems.
1. Historical Evolution of Oocyte and Embryo Donation 5
SUCTION--.
r.-J
SUPPLY
FIGURE 1.2. Uterine catheter utilized for recovery of embryos fertilized in vivo. The
supply (internal) line delivers tissue culture media into the uterine cavity where it
dislodges the embryo from the mucus in which it is floating. The media is recovered
through the outside line and delivered into a flask. The fluid is then scanned to
recover the embryo.19 Reprinted with permission from Sauer et aU 9
Sources of Embryos
For several reasons, donor in vitro fertilization evolved as the principal
source of oocytes and embryos during the latter 1980s. First, the oocyte
retrieval precludes the donor being exposed to any infectious diseases (e.g.,
HIV) that might be carried in sperm. Second, pregnancy rates with in vitro
fertilization improved considerably during recent years. A major objection
to donor in vitro fertilization during the initial years was the need for lap-
aroscopic oocyte retrieval. Because only extraordinarily compassionate oo-
cyte donors would likely submit to laparoscopic retrievals, there were ini-
tially severely limited sources of oocytes, namely, other infertility patients
and women undergoing tubal sterilization. 28 ,29 This problem was obviated
with the introduction of transvaginal oocyte aspiration. 28 ,29 The introduction
of ultrasound aspiration in the late 1980s made oocyte retrieval an office
procedure that is far more acceptable to anonymous oocyte donors than
laparoscopy would have been. Ultrasound-guided aspiration is the method
principally used today.
Synchronization of donors to recipients remains a challenge. Pivotal to
devising a successful strategy was appreciation of a window of endometrial
receptivity for embryo donation, initially cycle days 17 through 19, later
extended to include cycle days 15 through 20. 28 ,30,31 Synchronization is a
relatively simple matter in patients with ovarian failure but a far more dif-
ficult issue in recipients with intact ovarian function. Initially, natural cycles
6 John E. Buster
Indications
Compromised ovarian function from premature ovarian failure, gonadal
dysgenesis, sequelae of cancer chemotherapy, and oophorectomy were
seen initially as the principal applications for oocyte and embryo dona-
tionY>-lB,2B,29 Pregnancy rates were indeed gratifying. 16-18,28,29,35 Two addi-
tional indications later became evident. One is the application of oocyte
donation to women at high risk for transmission of genetic disease. This is
gratifying because it all bu_t eliminates that risk. 35 The second was the ap-
plication to older infertile women, even those beyond natural meno-
pause. 36-43 The magnitude of this application for infertility, though not ini-
tially envisaged, has been perhaps a most visible and sometimes
controversial venue. Sauer et al. have explored the application to older
women in a careful series of experiments. 36-39 This work, and that of others,
demonstrates that oocyte aging is the principal culprit in the decreased
reproductive efficiency in aging women and that the uterus and endome-
trium are secondary and probably play minor roles. 36-39
The Future
Oocyte and embryo donation is likely to playa major role in treating in-
tractable problems of diseased oocyte function. Donor oocytes should be-
come much more readily available as techniques for ovarian tissue culture,
in vitro maturation, in vitro fertilization of such oocytes, and cryopreser-
vation of oocytes are introduced. Continued laboratory research is needed
to reduce these methods to clinical practice. Even though women will prefer
to bear children with their own genetic characteristics, for many there is no
better choice. For families who benefit, each birth is an epoch event.
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