More on Donor Eggs

It helps to read the instructions…carefully. This afternoon I was helping my son, Aaron, assemble a new baseball pitchback that he received as a birthday present. We read the instructions and quickly assembled the aluminum frame with the little shock cords that would hold the net in place. Suddenly we stood back and noticed that we had completely goobered the thing up and had to pull it apart and start over. The problem was that we were too anxious to get the pitchback pulled together and had not really read the instructions carefully. Couples that jump into egg donor IVF can sometimes experience the same phenomenon.

The decision to use an egg donor is a very profound one and should not be taken lightly. The ASRM recommends that all women and couples using donor gametes (sperm and eggs) undergo psychological counseling. Although this is not a “pass-fail” type of evaluation, sometimes the couple takes stock of their situation and decides to hold off on donor egg or pursue adoption. The good news is that from a biological prospective, there is no rush as the uterus doesn’t lose its ability to carry a pregnancy.

So as we continue this donor egg discussion let’s go to the “Question of the Day.”

82. What are egg donors, and how is donor egg–IVF performed?

Donor egg–IVF involves the use of healthy female egg donors who are usually in their twenties. Most donor arrangements are anonymous, although known donor egg IVF is possible. In the latter case, the known donors are usually family members or friends. In our experience, most of our patients prefer to use an anonymous egg donor to avoid family and interpersonal conflicts.

Most medical practices recruit egg donors for their patients, but third-party agencies are also available that act as brokers. The American Society of Reproductive Medicine (ASRM) has developed a set of egg-donor screening guidelines, which most practices utilize for screening donors. The guidelines encompass comprehensive screening for infectious and genetic diseases, physical examination, and psychological testing. Since May 2005, the U.S. Food and Drug Administration (FDA) has mandated extensive infectious disease testing in screening all anonymous egg and sperm donors.

The actual treatment cycle for donor-egg IVF essentially combines a fresh IVF cycle (the donor) and a medicated FET cycle (the recipient). The two treatment cycles are synchronized by using GnRH analogs. Usually, the recipient begins estrogen therapy 5 days prior to the start of the egg donor’s stimulation so as to provide an adequate time frame for the recipient’s endometrium to grow and thicken. After 10 to 14 days of stimulation, the donor receives an injection of HCG (Pregnyl, Profasi, Ovidrel) to mature her eggs. On the same day, the recipient starts progesterone therapy to create a receptive endometrium.

Because most egg donors are young, they tend to respond very well to the ovarian stimulation drugs, producing many high-quality eggs and embryos. Implantation rates with these embryos are also very high, so that usually only one or two embryos are transferred to the recipient. Pregnancy rates usually exceed 50% per initiated cycle, making donor-egg IVF the most successful therapy currently available for infertile couples. Usually, extra embryos that were not transferred can be frozen and stored for later transfer, with excellent pregnancy rates achieved in subsequent conception attempts.

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Donor Eggs

Although I am a bit introverted and so is my wife, we occasionally venture out to parties and when people hear that I am a fertility doctor they often ask about the latest 63 year old or 67 year old who got pregnant. However, they all seem shocked to learn that the pregnancy was obtained with donor eggs. Human reproduction is very dependent upon the age of the female partner. This burden is not fair. It is not fair that Senator Thurman can father a child in his 80s but there you have it. Occasionally women in their late 40s will conceive and deliver but this is a rare event. The miscarriage rate for women over 40 years old with their own eggs is 50%. That is independent of how they conceived.

During medical school, one of my classmates, who was 35 years old and had children found out that her mother was pregnant spontaneously at age 55! We all ran to the Guinness Book of World Records only to discover that this was not even that close to the record of 57 years 120 days. So my classmate ended up with a baby brother 35 years younger than she was…poor kid (no offense Grace!).

So how about egg donation? Let’s spend the next few days reviewing aspects of egg donation. This topic is on my mind given the fact that I will be on Cable TV this afternoon (not sure when the segment actually airs) speaking about older women and pregnancy. I will let you know when the spot airs so someone besides my Mother can check out my new haircut. Meanwhile, here is the “Question of the Day” from the book that makes all other fertility books out of date…


81. Why does my reproductive endocrinologist think that I need to use an egg donor?


A woman is born with all of her eggs and is incapable of making more over the course of her lifetime. After the age of 30, her fertility begins to decline—markedly so after the age of 35. By age 40, most women will experience infertility.

Egg quality can be assessed, to a limited degree, by obtaining blood hormone levels for FSH and estradiol on cycle day 3. Elevations in either hormone suggest diminishing ovarian reserve. Another test for ovarian reserve is the clomiphene citrate challenge test (CCCT), a simple blood test that measures FSH and estradiol before and after the woman takes Clomid. Many reproductive endocrinologists perform an ovarian transvaginal ultrasound examination and a follicle count to further assess ovarian function. Often, the blood FSH, estradiol, and follicle counts are normal, yet the woman fails to respond to treatment. Thus normal hormone levels can be misleading—but abnormal levels usually suggest that an egg-related problem truly exists. When a woman’s eggs fail to respond adequately to treatment, when the woman has failed to conceive with previous attempts at IVF or other treatments, or when she has abnormal ovarian reserve, then IVF using donor eggs is an excellent option.

Since 1984, egg donation has been a cornerstone in treating patients whose eggs have deteriorated either through the normal aging process or because of disease. By using donated eggs from a woman in her twenties, the infertile patient essentially restores her fertility potential to that of her egg donor. Similarly, the miscarriage rate drops from more than 50% for patients older than age 40 to 10% to 12% with the use of donor eggs.

Egg donation has been used extensively in patients who are perimenopausal or even menopausal. Most clinics enforce an age restriction in terms of their egg-donor recipients, with the most common cut-off age being 50 years old. Unlike the eggs, the uterus does not age and remains receptive to implantation (as long as the endometrium is successfully prepared with hormones) well into a woman’s fifth and possibly sixth decades of life.

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Vanishing Twin

As fertility providers we have become victims of our own success with the rate of twin pregnancies rising to very high levels as IVF laboratory techniques improve. I view twins as an OK outcome but honestly, if I was never responsible for another twin pregnancy I would be ecstatic. The problem with twins is that the rate of preterm labor, preterm delivery and pregnancy related problems are not insignificant. Not all twins end up as cute little Santas on the family’s Christmas card. Some twin pregnancies end in the mid trimester or in the early 3rd trimester. The babies can do well if delivered at a hospital with a good NICU but we would all prefer term, healthy, 7 pound babies.

Sometimes twin pregnancies “auto-reduce” to singleton pregnancies and that is the topic of today’s “Question of the Day.”

79. When I went in for my first ultrasound after IVF, my RE saw two gestational sacs at 6.5 weeks, but only one had a fetal pole with a heartbeat. What will happen to the other pregnancy sac?

Such events are not uncommon following IVF. The incidence of a clinical twin pregnancy after IVF is 10% to 25%, with the exact likelihood depending on the number of embryos transferred and the age of the patient. In 30% to 40% of these pregnancies, one gestational sac will be empty, a situation called a blighted ovum pregnancy. Often, these pregnancies will simply disappear. At other times, the woman may experience cramping and bleeding. In such a case, there is a 40% to 50% risk that the healthy gestational sac and fetus will also abort. There is no way to predict the outcome, and there is no medical intervention that can be implemented to preserve the normal sac and fetus. During this difficult time, patients are well advised to rest and decrease their stress as much as possible. Supplemental progesterone may help quiet uterine contractions, but it is not curative. In women who suffer a twin early pregnancy loss, a medical investigation may be indicated to search for any organic causes that may have contributed to the early pregnancy loss. Unfortunately, such evaluations usually do not produce any definitive answers.

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A Capitol 4th of July

As I worked my way to downtown D.C. for the 4th of July Parade on Constitution Avenue, I consulted several maps in both the Metro stations and on the train itself. Once at the Federal Triangle stop there were several very helpful Metro employees directing pedestrian traffic and answering questions. The combination of the maps and the personalized attention made my trip less stressful and more efficient as I made the trip from my office (after 1 IVF retrieval and 3 embryo transfers) in much less time than I anticipated.

The journey that patients are taking as they pursue fertility treatments is a lot more involved than the one that I took this morning (and it costs a lot more than a Metro Farecard). However, both maps and personalized attention can make for a better trip. My hope is that this blog and the forthcoming book “100 Questions and Answers about Infertility” are the maps that may help…but the personalized guide is up to you to find (more about that in a future post).



49. How would I know when to pursue more advanced fertility treatments?


The decision to seek out more advanced fertility treatments is a complex question, and multiple factors must be considered when making it. For most couples undergoing treatment with IUI (either alone or with fertility drugs), the best chances for success usually occur within the first four treatment cycles. After that, the likelihood for pregnancy decreases. In many of our patients, we recommend only one or two IUI treatments. If these efforts are unsuccessful, we suggest that the couple proceed with other more aggressive treatments including both natural cycle IVF and traditional IVF using injectible fertility medications.


For some patients, IUI should rarely be utilized. For example, those couples with severe tubal disease, pelvic adhesions, or severe male factor infertility may do best by directly proceeding with IVF as their first treatment option. If an age factor must be considered or if the couple has prolonged infertility (infertility lasting more than 5 years), we may recommend IVF first or attempt just a few treatments with IUI before moving to IVF.

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Ovulation Woes

One of the most satisfying parts of being an RE is the fact that I can usually predict exactly where a patient is in her menstrual cycle with a blood test and a sonogram. Obstetrics is not nearly this precise. Some women deliver vaginally who you predict would have needed a Cesarean section and others need a Cesarean when you would have predicted a vaginal birth without any help at all. There is no way to predict what will happen in labor, it is all too crazy for me.

During my Fellowship at UCSF I used to moonlight once in a while at the Palo Alto Medical Clinic covering Labor and Delivery for a weekend. It was overwhelming to me. I could not stand to be at home while a patient was in labor, but I was bored at the hospital if labor was going slowly. My wife threatened to kill me. Since she was gainfully employed in the Department of Civil Engineering as an Assistant Professor, we came to the conclusion that it just wasn’t worth the stress.

Of course, one big question is how could you ever leave the perfect climate of Palo Alto, but instead let’s talk about ovulation. Here is today’s “Question of the Day” from 100 Questions and Answers about Infertility:

21. What prevents a woman from ovulating normally?


Regular ovulation is associated with regular menstrual cycles. Predictable monthly periods result from the release of an egg 2 weeks prior to the shedding of the endometrial lining of the uterus and in the absence of pregnancy. If a woman has irregular and unpredictable cycles, then she probably is not ovulating normally. Ovulatory problems are usually divided into two main categories: problems with the ovary and problems with the signals from the brain to the ovary. If a woman’s irregular cycles result from a lack of follicles within her ovary, then the failure of the ovary to respond will cause the pituitary gland to secrete increased amounts of follicle-stimulating hormone (FSH). Women with elevated levels of FSH are described as having diminished ovarian reserve; if their periods cease entirely, then they are described as having premature ovarian failure (POF). Different laboratories may vary as to how they define an “elevated” level of FSH, so a discussion with your physician is crucial to correctly assess the results of this test. In most cases, however, an FSH level of more than 15 IU/L is evidence of diminished ovarian reserve; FSH levels exceeding 30 IU/L usually signify POF. If a woman has a normal complement of follicles but still does not have normal cycles, then the problem must lie elsewhere. Most such women suffer from a communication mismatch between the brain and ovary, which disrupts the carefully coordinated hormone signals that induce the growth of ovarian follicles. The causes of this disruption can be further classified, with most patients being found to have polycystic ovarian syndrome as opposed to other hormonal imbalances.

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Pink or Blue- Can We Choose?

Few issues in reproductive medicine are as controversial as gender selection. As the father of children of both genders I can certainly understand the desire for family balancing. However, few concepts are as disturbing as abortions performed on the basis of fetal gender alone. After my two sons were born, we figured that we would probably only have boys if we continued to add to our family. Then came pregnancy #3 and after a bunch of ultrasounds performed by yours truly, I was pretty sure that there was a change in the wind and we were having a girl. We confirmed this at 18 weeks with an anatomy sonogram and Leah was born in December 1997 (in New York to boot which made it hard on me given my Boston roots). To this day she loves to call herself a New Yorker, for reasons that are beyond me.

In any case, although the “Question of the Day” could be “Why are the Red Sox losing so many games?” I will keep to the subject at hand as we discuss gender selection.


17. Can I choose the sex of my baby?


Gender is determined at the moment of fertilization, when a sperm bearing either an X or Y chromosome penetrates the egg, resulting in formation of either a female or male embryo, respectively. The event is random, and the sex ratio of females to males conceived is fairly even. Several techniques exist that can enhance the likelihood that a couple will conceive a child with the desired gender. The Ericsson method is a simple, noninvasive method that separates X-bearing sperm from Y-bearing sperm using centrifugation techniques. The sperm are placed on the top of a column of either albumin or Sephadex, and the specimen is centrifuged to isolate the desired gender-selected sperm. These sperm are then placed in the female partner through in-office artificial insemination. The success rates reported with this method vary from no benefit to as high as 75% for the desired gender. The Ericsson method is not associated with any known risk to either baby or mother.

A newer experimental technique (Microsort) involves the labeling of the DNA of the sperm, followed by passage of the sample through a cell-sorting machine. This process yields a smaller sperm sample than the Ericsson method, and IVF with ICSI may be required for pregnancy. Nevertheless, the results appear encouraging in terms of gender selection. The gender of a child can also be selected using IVF and preimplantation genetic diagnosis (PGD). This technique is expensive and much more complex than the Ericsson method, but success rates for the selected gender routinely exceed 90%. Couples who elect to pursue IVF and PGD for gender selection often do so to prevent genetically inheritable medical diseases, such as Duchenne muscular dystrophy, from occur- ring in their children.

Many medical authorities consider gender selection to be unethical except in a few circumstances, such as when the couple runs a high risk of having a child with an inheritable medical disease. Gender selection may also be used when a couple has at least one child but want to limit their family size and desire a child of the opposite gender.

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How Normal Reproduction Works

Sometimes it seems incredible to me that any humans ever conceive given the complexity of reproduction and the multitude of factors that can prevent conception. As fertility physicians we always need to keep in mind how the normal system works in order to evaluate for problems and suggest therapeutic interventions. Personally, I have always felt very privileged to work with patients seeking fertility. The rewards are great but the emotional costs can be high for both patient and caregiver. The news is sometimes not good and the treatments can be expensive and invasive. Unfortunately, the more expensive and invasive treatments work better than the less expensive ones. Sometimes, this point is hard to get across.

DrG: I am sorry that the IUI didn’t work. But remember that I thought the chance of pregnancy was only about 5% per attempt.

Patient: So why didn’t it work.

DrG: Well, it only works 5% of the time and this month you were in the bad 95%.

Patient: But why didn’t it work for me this time.

DrG: Because most of the time it unfortunately doesn’t work given your situation.

Patient: But I want it to work.

DrG: I understand but unfortunately this is not a very successful option. IVF works better.


Patient: But I don’t want to do IVF.


DrG: Well then we can stick with this option but it only works 5% of the time.

Patient: But I want something that works better.


DrG: IVF would work better.


Patient: But I don’t want IVF.

DrG: Then we are unfortunately a bit limited by the situation given your particular case.

Patient: But I want to get pregnant.

DrG: Then we should consider additional IUI cycles or move to something more intensive…


Patient: But I don’t want to do additional IUIs and I don’t want something more invasive.


DrG:


I am not unsympathetic to patients who are stuck between a rock and a hard place, but there are always trade offs in life. For example, you could read this blog every day until I work though all of the questions or you could go to Amazon.com and preorder the forthcoming "100 Questions about Infertility." If you do the latter then I will have 37 cents more to spend the next time I go to the Safeway down the street. If you are the former, then print out this post and start making your scrapbook:

1. How does normal human reproduction work?

Norman human female reproduction depends on the correct functioning of four components of a woman’s body: the brain, the ovary, the fallopian tube, and the uterus. At the time of her birth, a woman’s ovary contains all of the eggs that she will ever have. These eggs are contained within fluid-filled sacs called follicles. Every month, the brain sends out a signal from the pituitary gland (a gland located at the base of the brain) stimulating the follicles to grow. Not surprisingly, this hormone is called follicle-stimulating hormone (FSH).

Under the influence of FSH, a group of follicles begins to grow, but by the fifth day of the reproductive cycle a single dominant follicle has already been selected. This dominant follicle may be either on the right ovary or the left ovary. As it grows, the follicle produces an important steroid hormone called estrogen. Estrogen causes the lining of the uterus (endometrium) to thicken in anticipation of the eventual implantation of an embryo. By mid-cycle, this follicle has grown to a diameter of 20 to 22 mm. At this time the brain releases a second hormone, called luteinizing hormone (LH), from the pituitary gland. LH is the trigger that induces ovulation. Approximately 36 hours after the LH surge, the follicle releases the egg.

It is the job of the fallopian tube to trap the egg. If the fallopian tube fails to catch the egg, then pregnancy cannot occur. During intercourse, tens of millions of sperm are deposited in the woman’s vagina when her male partner reaches orgasm and ejaculates. While the egg is safely held within the fallopian tube, these sperm may swim from the vagina, into the cervix, through the uterus, and up into the fallopian tube, where fertilization can occur.

Normally, a fertilized egg travels through the fallopian tube for 5 days after fertilization, at which point it reaches the uterus. (A fertilized egg that remains trapped within the fallopian tube is called a tubal pregnancy or ectopic pregnancy, and can be a life-threatening condition.) It divides many times along the way. By the time it reaches the uterus, it has grown to hundreds of cells and is called a blastocyst.

Once the egg is released from the ovary, the follicle (now called a corpus luteum) produces both estrogen and a new hormone: progesterone. Progesterone changes the estrogen- primed endometrium, allowing implantation of the embryo and thus permitting pregnancy to occur. If a pregnancy does not arise, then 2 weeks after ovulation, the levels of estrogen and progesterone both fall and a menstrual period ensues, in which the woman’s body sheds the lining of the uterus. Menstrual flow lasts approximately 3 to 5 days in most women. Overall, human beings are not very fertile, with maximum pregnancy rates of only 20% to 25% per cycle during the years of peak fertility (the second and third decades of life).

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