While I have written that it is easier to get pregnant when you’re younger than when you’re older, and have urged women in their thirties not to delay high-tech treatment until it is too late, I’m going to turn around completely now and point out that if you do delay too long and you have run out of eggs and entered menopause, it is really still not too late to have a baby. All that is needed is an egg donor, and you can still carry your own baby in your late forties or fifties, or even sixties.
I recently saw a woman in her forties who first got pregnant seventeen years ago, and because she was not married had an abortion. She went on the birth control pill for ten years and finally fell in love and had a happy, stable marriage. She had been trying unsuccessfully to get pregnant in that marriage for six years. She had irregular, only occasional periods and was clearly about to go into menopause. We tried stimulating her with high doses of gonadotropin but were unable to get any eggs. When I delicately suggested the idea of giving up on her eggs and using a donor, she surprised me with her complete absence of anguish. She jumped up with excitement and told me immediately that she had in mind two or three very good friends who were in their early thirties who she felt would be happy to donate. Sometimes one can find close friends or younger sisters who are more than happy to donate an egg. However, in the majority of cases we have to find and match egg donors for such patients.
Naturally, if you receive a donor egg, the genes of the baby will be a combination of your husband’s genes and those of the woman who donates the egg, even though you will carry the baby for nine months and deliver it. What are the psychological consequences of your carrying a baby that is genetically not your own? This has been asked since 1983, when the first case was reported in Australia. I can say unequivocally that carrying that baby for nine months results in a solid, loving bond between the mother and the child, regardless of the genetic origin of the donated egg. This is not greatly different from the donor sperm situation discussed in the last chapter, except that donor eggs are even more favorable for bonding, because the mother identifies with the baby (regardless of genetic origin) by carrying it. I would like to refer you back to the previous chapter, in which I talk about the issues of emotional bonding with the child, and where the child’s personality, intelligence, value system, and even athletic ability come from—genes or environment. Donor sperm is only occasionally used these days because of ICSI, and donor sperm requires much deeper psychological preparation than donor eggs. Donor eggs never have led to any problems, in our experience. The fact that the child has been carried for nine months in the uterus results in solid bonding between mother and baby, regardless of the genetic origin of the egg.
The medical world was initially shocked to hear about the first pregnancy using an embryo from a donor egg, which was achieved in a menopausal woman at Monash University in Melbourne, Australia, in 1983. Dr. Peter Lutjen, Dr. Alan Trounson and their colleagues were the innovators of this idea. These brilliant reproductive scientists from Australia established what then seemed to be the impossible system of hormonal replacement for the menopausal woman that allowed her uterus to behave just like that of a woman in her twenties, permitting implantation of an embryo despite the fact that she had no ovaries to make the hormones which are normally necessary to sustain a pregnancy in the first three months.
Much older women (late forties and fifties) have no difficulty getting pregnant (greater than a 50 percent pregnancy rate per cycle) so long as the donor eggs come from young women. The age of the uterus is not what is significant in the high pregnancy rate of these patients, but rather the fact that: 1) the eggs came from healthy younger women, and 2) the recipient’s only infertility problem was that she had run out of fertile eggs. With these two operative factors, pregnancy rate using IVF and donor eggs in menopausal women is over 50 percent, no different than what one would expect in younger women. The main determinant of pregnancy rate is the age of the woman from whom the eggs originate.
Women as old as sixty-three years of age have gotten pregnant quite easily with egg donation and have delivered healthy, happy babies. The oldest mother on record was reported by Dr. Richard Paulson in April of 1997. Dr. Paulson normally will not perform egg donation for women over fifty-five years of age, but this healthy-looking sixty-three-year-old woman successfully lied in order to get into the program. Although she was only two years away from being eligible for Medicare, she had no trouble conceiving and carrying the pregnancy normally because the eggs came, of course, from a younger woman.
Many of these older women getting pregnant with egg donation have multiple and often large fibroids in the uterus. These fibroids completely distort the uterine shape, and in prior decades they were thought to be a cause of infertility. On the basis of the ease with which these women become pregnant with donor eggs and deliver healthy babies, it is now apparent that the vast majority of uterine fibroids, no matter how large, have no effect on a woman’s fertility, and should not be overzealously operated upon. In fact, the only fibroids that should be removed for fertility are those that are occasionally found upon hysterosalpingography to be inside the cavity of the uterus. We have had many older patients with large uterine fibroids become pregnant with donor eggs and deliver healthy babies.
Many women in their late 30’s and early 40’s who have run out of fertile eggs initially resist adamantly the suggestion of using donor eggs. They may insist on going through one unsuccessful IVF cycle after another, unwilling to even consider donor eggs. Eventually, years later, most of these women request donor eggs. Many of these women become like personal “friends” of the clinic because we come to know them so well. Despite years of negative feelings about the idea, all of them are overjoyed when they finally have a baby via donor eggs. We have no unhappy experiences with this.
There are basically three different ways of organizing an egg donor program. One approach is with anonymous shared egg donors. That means that younger women undergoing IVF who have extra eggs agree to give some of them to menopausal women who are on a waiting list. The recipients are placed on the appropriate estrogen and progesterone regimen to synchronize their cycles with the women who have the extra eggs to give.
The next approach is similar to that of running a sperm bank. The egg donor is paid a fee. The donor’s cycle is synchronized to that of the recipient just like with gestational surrogacy (see table 17.1).
This can either be anonymous or with full disclosure. There are some possible ethical problems associated with this approach in that women are paid to undergo drug therapy and invasive follicle aspiration to donate eggs to someone they don’t know and don’t care about. In other words, they are taking a medical risk (however slight) simply for pay. However, with proper counseling, this has also turned out to be a very positive experience both for donor and recipient.
For example, a 50 year old patient from an Asian country needed egg donation. In addition, her husband required a TESE procedure to find in his testicles the very few sperm that were being produced. Obviously, finding an appropriately matched egg donor for her would have been very difficult using anonymous shared oocytes from the pool of patients coming through an IVF center. However, using an agency dedicated to searching for young volunteer egg donors and doing appropriate screening and psychological evaluation, we were able to locate the perfect match for her. The recipient of course had to pay for all of the donor’s expenses plus legal and agency fees. But this cost was still far less than that incurred for adoption. These wonderful people are now happy parents despite being discouraged by their doctors at home from ever trying to have a baby, because they thought he had no sperm and that she had no eggs.
A third approach is for patients to search among their younger friends or relatives for someone who is willing to donate an egg, to make all the legal arrangements privately with them, and then to go through a screening and counseling evaluation. This is a “non-anonymous” program, and no one is being paid, but rather the gift is being made as an act of love.
IS IT ETHICAL?
Our first egg donation case in the mid-80’s prompted consternation by some administrators and “ethicists” who feared the future, but was endorsed enthusiastically by the patients, their doctors, their parents and grandparents, and even by the clergymen who represented the patients. A 28 year old woman had lost both of her ovaries as a teenager because of surgery for benign ovarian cysts. Her 24 year old sister had always felt sorry and guilty that she would be able to have children, and her older sister would not. She and her family brought the idea up to us of egg donation and despite some concern and trepidation, it felt right to me. This was the beginning of what has been one of the most personally and emotionally rewarding aspects of my medical practice. The sister with no ovaries conceived healthy twins who are now grown and happy young women, who might not exist today if we had reacted negatively to this unusual sounding first request.
A year later we were challenged once again to ponder the ethics of an even more complicated patient request. A 40 year old woman who was a very prominent lawyer had run out of eggs, and was married to an equally prominent lawyer who had no sperm. They were real experts on family law. They desperately wanted a child and preferred to preserve the genetic lines of their family. He had one younger sister and she had one brother. Her brother offered to donate sperm, and his sister offered to donate eggs. Thus the embryos generated by his wife’s brother’s sperm and his sister’s eggs, allowed them to continue their family line, and avoid consanguinity.
I was confronted years ago by a nurse who had gone through menopause, early, was now 42 years old, and who strongly wanted to have a child with her husband knowing full well that it would require donor eggs. Yet she was very intellectually bothered by the idea of bringing technology into the process of getting pregnant. She was a very deep and “new age” spiritual person who just feared the mingling of technology and conception. I remember telling her to read “Zen and the Art of Motorcycle Maintenance”. She was surprised that a conservative physician would have even read such a book, but our bond of trust as doctor and patient was immediately sealed. She and her husband now have a gorgeous and intelligent daughter, and it matters not to her or her husband that the conception was the result of technology.
The egg donor does not necessarily have to be young. Many years ago we saw a 43 year old extremely successful business woman from the West Coast who had gone through several failed IVF cycles. She had a relatively good ovarian reserve for her age (8 eggs retrieved in previous unsuccessful IVF cycles in her home city). Her sister was 42 years old and looked just like her. They suggested that we stimulate them both simultaneously for IVF, and use all of the eggs retrieved, both from the patient and from her sister. She did not care which eggs resulted in the baby, hers or her sister’s, and her husband did not care either. They just wanted to maximize their chance for pregnancy despite her age and her sister’s age by using all of their combined eggs for her IVF cycle. As it turned out, we got eight eggs from her and nine eggs from her sister. She became pregnant and delivered a healthy baby. She has no idea if it came from her egg or her sister’s egg, and she could care less.
HOW IS IT DONE?
We need to talk further about the technical aspect of: 1) synchronizing the cycles of the donor and the recipient, and 2) giving the proper hormone replacement to recipients so that their uterus is prepared for implantation of the embryo and also to maintain the pregnancy until such time as the placenta starts making its own hormones by eight to twelve weeks of pregnancy. Once again, you should look at table 17.1 because the protocol is virtually no different for surrogate uterus cases than for egg donation cases.
The difference is that in the surrogate uterus case, the recipient is not the patient but rather the helper, and in the egg donation case, the recipient is the patient and the donor is the helper. The only other difference in the protocol is that if the recipient is truly menopausal, she does not need to be placed on birth control pills, and she does not need to be placed on Lupron, because she is simply not making hormones at all. She would begin Estrace, however, on the same day that you see on the cycle chart in this chapter. It is all timed out with the same goal in mind, that the recipient first receives proper estrogen priming of her uterus, and then one day after the donor receives her HCG injection the recipient begins taking progesterone injections in addition to the estrogen. This assures that the IVF transfer will be performed at that time in the cycle where the window of receptivity for egg implantation is open. Between day four and day six of progesterone replacement is when the day 3 embryo must be placed into the uterus.
Even after it is clear that you are pregnant you will have to stay on estrogen and progesterone supplements for up to twelve weeks longer, until the normal time in pregnancy when the placenta takes over the function of the ovary and produces all of its own self-sustaining estrogen and progesterone. This may require considerably less than twelve weeks, and the latest data indicate that by six weeks (contrary to our previous thinking) the placenta may be making enough estrogen and progesterone to sustain the pregnancy. The way to determine that is to get blood tests every week for estrogen and progesterone levels, and when the progesterone level begins to rise dramatically over what we know you’re getting from replacement, then we know the placenta has taken over and you no longer need to take hormone replacements. However, most infertility physicians, including me, feel safer if you stay on the estrogen and progesterone for a full three months just to be safe.
SURROGATE UTERUS (YOUR MOTHER CAN HAVE YOUR KIDS FOR YOU)
In 1980, I received a very sad letter from a twenty-five-year-old woman in the Bronx, New York, saying that when she had surgery for uterine fibroids, the doctor had to perform a hysterectomy, and she lost her uterus. Now she desperately wanted to have children. Unfortunately, at that time, I had to write to tell her there was no hope. I had predicted in my original book in 1979 that with the “new” in vitro fertilization technology on the horizon, perhaps at some time in the future a woman without a uterus could have someone else carry her genetic child for her. But by the time this futuristic medical prediction became a reality, this lady had already run out of eggs and was in menopause. (Of course today we can solve that problem, too, as you have seen in the first part of this chapter).
HISTORY OF GESTATIONAL SURROGACY
In 1985, Dr. Wolf Utian and Dr. Leon Sheehan from Cleveland reported the first successful case whereby a woman with no uterus whatsoever was able to have her own genetic child. The story of that first case, reported in the New England Journal of Medicine, was absolutely spellbinding: A thirty-seven-year-old woman became pregnant, but the uterus spontaneously ruptured at twenty-eight weeks of gestation, necessitating a cesarean section and a hysterectomy. The baby girl subsequently died and the woman was left childless and without a uterus. The couple, however, remained strongly committed to having their own genetic child and the wife asked that an embryo of hers be transferred to the uterus of a friend who was interested and willing to carry the child as a surrogate. The friend was a healthy, married young mother of two. The reproductive cycles of the two women were synchronized (this will be explained later). The patient’s eggs were incubated with sperm from the husband, and three days later an eight-cell embryo was transferred to the uterus of the surrogate. The surrogate became pregnant and nine months later delivered the healthy genetic baby of her ecstatic friend.
At the American Fertility Society meeting in 1986 a lady introduced herself to me and thanked me for the prediction that I made in my original book about gestational surrogacy. She told me it had prompted her to go to the in vitro fertilization program in her community where she told them what she would like. Performing this kind of procedure is so simple that it turned out not to be a problem, and indeed, when I saw her at that meeting, her best friend was already pregnant with her genetic baby and ready to deliver and give it to her.
CASE HISTORIES OF GESTATIONAL SURROGACY
A few years later I took care of a famous pair of sisters who were written up in Good Housekeeping magazine. Linda had gone through many failed attempts at in vitro fertilization in other clinics. Her sister had already had several children without any problem and was quite willing to carry a baby for her. We were able to obtain six embryos from Linda’s eggs and her husband’s sperm. We put three embryos into Linda and three embryos into her sister, so as to hedge our bets. As it turned out, both sisters conceived, one with twins and the other with a singleton. The twins were born in December, and the singleton was born in January of the subsequent year. Thus triplet siblings were born safely in different cities and in different years. The surrogate sister, of course, gladly gave the children back to their genetic parents. She has always felt a very deep and close relationship, as a special kind of aunt, to the niece and nephew she carried for their mother.
We were approached by a twenty-nine-year-old woman who had her uterus and both ovaries removed, and desperately wanted to have a child. Her husband had perfectly normal sperm, and they both wanted a baby by her husband’s sperm. The question for this patient is who would provide the eggs and who would provide the uterus? In her family, one of her sisters was willing to donate an egg, the husband of course would provide his sperm, and another sister would allow the eggs and the sperm to be transferred to her so that she could carry the baby. This couple now has a beautiful daughter, with two special aunts, one who provided the eggs, and one who carried her. Thus, with an open attitude, and loving friends and family who are willing to help, virtually anybody can have a baby.
The laws in every state in the union clearly ensure that if the husband is living with his wife when she gets pregnant, no matter whether the sperm came from him or not, he is the father of the child. The laws also ensure that if a woman carries her own genetic baby as a surrogate for another couple, she does not have to give it up involuntarily. Therefore a surrogate for another couple must not be the egg source also. That is, to be a surrogate, a woman must not be the genetic mother. However, the egg donor must not also be the surrogate. The laws are very consistent with what makes biological and psychological good sense. If the surrogate were also the egg donor there would be a severe danger of psychological “bonding” conflicts, regardless of the original intent of the would-be parents and the surrogate. However, as long as the egg donor and the woman carrying the baby are different, we have never had a conflict.
One of our earliest surrogate cases was a twenty-seven-year-old woman who had lost her uterus from a hysterectomy necessitated by severe bleeding occurring in her previous pregnancy. The only way the doctors could save this young woman’s life from this obstetric disaster was to remove her uterus. Yet she had normal ovaries and her husband had good sperm. What was the solution? As it turned out, her forty-eight-year-old mother was quite willing to serve as a surrogate uterus to carry her daughter’s baby. Their menstrual cycles were synchronized with birth control pills so that day one of the mother occurred simultaneously with day one of the daughter. The daughter was stimulated in the usual fashion for in vitro fertilization, her eggs were fertilized with her husband’s sperm, and her embryos were transferred into her mother’s uterus. Astoundingly, the forty-eight-year-old mother became pregnant with her daughter’s twins. Nine months later, she gave birth to two healthy grandchildren whom she then immediately turned over to her daughter and son-in-law.
ETHICS AND LEGALITY OF GESTATIONAL SURROGACY
Surrogate uterus pregnancies are here to stay; they are morally and ethically completely proper, and they offer an opportunity for a relative or a loved one to give the greatest gift possible to a woman without a uterus. One forty year old patient of ours had already gone through four cycles of IVF elsewhere and failed to get pregnant. All of her doctors recommended that she give up, but she refused. She had gone through fourteen years of infertility treatment for bilateral tubal infections and “clubbed” tubes. Her main problem was that women with blocked fallopian tubes caused by infection are known to have lower pregnancy rates with IVF. There are many theories to explain this, including the possibility of retained toxic fluid in the blocked tubes, or even that some permanent but subtle damage has been done to the uterus by the infection. This woman had her tubes removed just to make sure that the former was not a problem. Nonetheless she failed to get pregnant with four IVF treatment cycles in another center and in her fifth IVF cycle with us. It was natural to attribute the fifth failure to her biological clock, since she was forty years old and pregnancy rates in forty year olds are much lower with IVF.
However, on the chance that her problem all along might be related to her history of tubal infection, her husband’s cousin (who had already had five normal pregnancies and five children and whose husband was vasectomized so they could not have anymore children) agreed at age 42 to be a surrogate for this patient. Our forty year old patient had such a poor ovarian reserve by this time (after fourteen years of trying to have children she was just about at the end of her biological clock) that we were only able to obtain two embryos. We transferred both of those embryos into her husband’s cousin and warned them that the prognosis was extremely poor. Nonetheless her cousin did become pregnant and delivered a healthy little baby girl nine months later. Despite the woman’s vastly reduced ovarian reserve after so many years of unsuccessful treatment, the problem all along was simply that because of prior infection her uterus was not receptive to implantation.
We’ve had many similar cases whereby the history of prior tubal disease has conferred a low pregnancy rate on couples, and after many failed attempts at pregnancy with IVF (to bypass the tubal blockage), resorting to a surrogate, who is usually a family member or close friend, solved the problem. Although removal of the fallopian tubes in these patients may improve their pregnancy rate with IVF, often it doesn’t. In women who have diseased fallopian tubes, if they don’t get pregnant on their own with several cycles of IVF, using a surrogate will be a simple solution to the problem.
In some cases it would be medically inadvisable for the patient to carry her own child, such as the Marfan’s syndrome patient I discussed in detail in a previous chapter. This was a woman who had a genetic disease that required her to have heart and blood vessel operations to protect her from sudden death, and who had to be on blood thinners because of these operations. A pregnancy for her would be fatal. Thus when she got married her mother came forward and offered to carry her babies for her. Not only was she able to safely have twins which her mother carried (i.e., her mother carried her own grandchildren), but we were able to perform genetic diagnosis on those embryos to make sure that neither of these two babies, which her mother carried, would have the risk of the same genetic disease that she had inherited from her father.
HOW IT IS DONE
Although the gestational surrogacy procedure is medically simple (now that you have read the rest of this book and understand how IVF technology works), I will outline the methods we use for synchronizing the cycles of the donor and recipient. This work had been going on for decades in cows before we applied it to humans. Embryos from highly prized cattle would be placed into the uterus of very low milk-producing cows, who would then give birth to prize heifers. Since embryos could be obtained every month, a prize cow could deliver twelve heifers a year via the uterus of surrogate cows rather than just one prize heifer a year. This vastly improved the efficiency of milk production in the world. Every time you go to the grocery store and notice how relatively inexpensive nature’s most perfect food (milk) is, realize that it is partly because of these reproductive advances.
In humans, the synchronization is a little more difficult than in cows. Both women are placed on birth control pills. These pills, started in the beginning of the follicular cycle, put the women “on hold” and can be discontinued at the same time for both of them. The key factor in synchronizing the cycles of donor and recipient is that the recipient must start on progesterone injections one day after HCG is given to the donor. The purpose of synchronizing the donor and recipient is that the endometrial lining of the recipient must be at the stage of development in the monthly cycle where it is receptive to implantation of the embryo at its stage of development.
If you look at table 17.1, you will see our protocol for synchronization, whether it involves a surrogate uterus or an egg donor, two clinically opposite situations. For both situations, this synchronization schedule works quite reliably. Both the donor and recipient are put on birth control pills to synchronize their cycles. The recipient also goes on Lupron so as to completely suppress her pituitary. On the first day the donor receives gonadotropin, the recipient starts on Estrace (an oral, absorbable form of natural estrogen). The recipient’s Estrace dose is 6 mg per day. Often an estrogen patch is also used to guarantee that an adequate uterine lining forms. The length of the artificial follicular phase during which the recipient is on Estrace and the patch is not important; the only significant factor is when she goes on progesterone. Whenever the donor receives HCG, which is often (but not always) on the tenth to twelfth day after gonadotropin has begun, the recipient starts on progesterone one day later.
This always allows the synchronization to time out perfectly for embryo replacement into the recipient. Keep clearly in mind that the donor-recipient synchronizing is exactly the same whether this is the case of gestational surrogate recipient, or in reverse, of a donor giving eggs to a patient with a uterus who has no viable eggs of her own.
Copyright © 2007 by Dr. Sherman J. Silber, M.D.
For more information on egg donation, please feel free to call us at (314) 576-1400.