By:
James Toner ,
MD, PhD
In order to become pregnant, healthy
embryos must be present in an appropriately primed uterus. In normal
reproduction and standard IVF, embryos and endometrium are
automatically in synchrony by virtue of the endocrine changes over
the course of the natural or stimulated cycle. However, for couples
in need of surrogacy, the source of eggs is different from the host
uterus. This makes synchrony between the two women, each with their
own menstrual cycle, problematic. It is unlikely that any two women
involved in this process would have egg retrieval (in the egg donor)
and ovulation (in the surrogate) on the same day; yet this
coincidence is exactly what is necessary to achieve this
synchrony.
Therefore, this synchrony between embryo stage and endometrial stage is usually accomplished by taking control of one of either the "embryo" or the "uterus". Control of the embryos is accomplished by cryopreservation ("freezing"). Control of the endometrium is accomplished by hormone replacement. In practice, this has typically meant that either:
1. fresh embryos are replaced in hormone replaced cycles, or
2. frozen embryos are replaced in natural cycles.
Both approaches has proved to be effective. It is not yet clear whether one is superior. Below I discuss some of the factors that influence the success of these different approaches.
Fresh embryos into the uterus after taking
hormones
Embryos that have not been frozen have not been subjected to the
stress of this process. Thus, on average, one would expect fresh
embryos to be more likely to implant than frozen embryos.
However, replacement of these embryos into a uterus primed with medications may not always lead to an appropriately prepared endometrium. Many methods of hormone replacement have been employed, and all seem capable of working. Early work on this approach confirmed that more than 90% of the time the endometrium appeared appropriate (by biopsy) following this replacement. Subsequent work has confirmed that the duration of estrogen replacement can be varied from as little as 7 days to as many as 28 with little if any effect on the receptivity of the uterus to embryo implantation.
It is important to note however that not every person treated in this way develops an appropriate uterine lining. Consequently, I would recommend that couples using this method ensure an appropriate response by having a vaginal ultrasound performed after 2 weeks of estrogen replacement. The thickness of the endometrium at this time should be at least 7 mm. If it is thinner, than the development is likely inadequate and no transfer should be performed until adjustments are made which thicken it up.
The advantage of this approach is that fresh embryos can be transferred into an adequately primed uterus. Disadvantages include the cost of medications, the lack of certainty about when the transfer will occur (since it depends of the ovarian response of the egg source), the possibility of inadequate endometrial development, and the need for all parties to be available at the same time. A further disadvantage to this approach is that it requires the surrogate to take supplemental estrogen and progesterone through the first few months of pregnancy, since the surrogate's own ovaries are not producing any. These medications do not increase the risk of miscarriage or birth defects, but do make for an additional inconvenience for the surrogate.
Frozen embryos into the uterus in a natural
cycle
An alternative is to use the surrogate's
natural cycle. In this approach, the surrogate takes no hormones,
either during the preparatory phase or after the embryo transfer.
This is more convenient for the surrogate.
In order to use this approach, embryos will need to have been frozen ahead of time. This is because it is not possible to predict when the surrogate's uterus will be ready to receive embryos until the last minute (actually, it is usually known 2 to 4 days beforehand).
The surrogate's cycle is monitored for follicle growth by ultrasound, and for the characteristic hormone changes that occur around ovulation. These include: a fall in estradiol level, an LH surge, the production of progesterone, and the collapse of the follicle. Based on these events, the team can plan the best day for embryo transfer.
The primary disadvantage of this approach is that frozen embryos are required. Freezing embryos does not improve their odds, but only reduces them. In most programs, about 30% of embryos do not survive the process of freezing and thawing. Thus, there is the possibility that upon thawing, no good embryos will remain. However, if there are good embryos, then this approach is effective and simpler for the surrogate.
Advantages include: no medications for the surrogate (and thus lower cost), more "natural" endometrial preparation, and the dissociation of the cycle of egg retrieval from the cycle of embryo transfer. This latter features makes scheduling easier for many couples interested in these arrangements.
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In summary, 2 methods of preparing surrogates for
embryo transfer are currently available. One can transfer fresh
embryos into artificially prepared endometrial cavities, or one can
transfer frozen embryos into the cavity during natural menstrual
cycles. Both methods have produced comparable pregnancy results to
date. Each has its own advantages and disadvantages.
December 1996
Copyright 1996. The American Surrogacy Center, Inc.(TASC), Marietta, GA
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