Assisted reproductive technology (ART) has been a part of modern medicine now for over 30 years and in the US alone over 132,000 IVF cycles were performed in 2007. All birth outcomes are reported to the Centers for Diseases Control but there is no mechanism for long-term follow-up of IVF births.

Well over a million babies have been born world wide through IVF and new data are emerging about reproductive birth outcomes after conception. Some countries, particularly the Scandinavian countries, do an excellent job on gathering data for all births, including IVF-conceived births. One of the greatest risks of ART is prematurity from multiple gestation. From several of these databases, it has become apparent that even singleton IVF births are statistically associated with poorer birth outcomes. Lower birth weights, pre-term delivery and infants small for gestational age (i.e. lower weight than expected for number of weeks in utero) are some of the findings from follow up of IVF babies.

These findings beg the question: is it something about IVF, namely the culture of the early embryo in a lab for the first three to five days of life, that results in these poorer outcomes, or is it something about the couples that need IVF to conceive that is associated with them? This can be a difficult issue to sort out because relatively few people undergo IVF who are not infertile.

A recent study from Norway was published in the British medical journal Lancet that tried to address this question by comparing IVF babies with their spontaneously-conceived siblings. The study compared 1,200,922 spontaneously-conceived live births and compared them with 8,229 live births after ART between January 1984 and June 2006. Of those women who had given birth to a singleton infant after ART, 2,456 also delivered a singleton infant after spontaneous conception. In 56% of the cases, the ART baby was born first and in 44% the ART baby was conceived after the birth of the spontaneously-conceived infant. The researchers looked at birth weight, gestational age as well as a number of other factors.

Compared with women in the general population that delivered a spontaneously-conceived birth, the women that delivered after IVF were older, less likely to smoke and had fewer previous births. Induced labor and cesarean section were more common in the IVF moms. The difference in birth weight between ART and non-ART babies was 131 grams (4.6 ounces). That is, the ART babies weighed, on average, 4.6 ounces, or about 3/4 pound less than the spontaneously-conceived babies. After statistical adjustment for gestational age, maternal age, prior births, year of birth, the difference in birth weight between ART and non-ART babies was 25 grams (0.88 ounces). The ART babies were born, on average, 3.7 days earlier than the controls. After statistical adjustment, the number of days of total gestation was 2 fewer days. Because of the large sample size, these were statistically significant differences but realistically, they were probably not clinically significant.

In comparing the sibling relationship ART vs. non-ART births, the differences were even smaller. The difference in birth weight was only 87 grams (about 3 ounces) for the ART babies as compared to their spontaneously-conceived siblings. The gestational age differences at birth were 1.3 days less for ART. After adjustment, these differences were only 9 grams and 0.6 days. These differences were not even statistically significant.

From these data, we can see that ART births do show statistical differences in some birth outcomes as compared to spontaneously conceived births. However, none of the differences seem are to an extent that would have any real clinical meaning. These differences tend to disappear to a large extent when comparing siblings from both spontaneous and IVF conception, suggesting that it is something about the families that utilize ART, rather than the technique itself that may be associated with the outcome differences.

In the press today we see that the “world’s oldest new mom dies” at age 69 (see our earlier blog post clarifying that PFC did not treat this patient), three years after giving birth to twins conceived through IVF. Maria del Carmen Bousada apparently lied about her age to the Los Angeles Physician who helped her become pregnant, creating a firestorm of criticism in the press.

The case demonstrates one of the most basic dilemmas that we face in helping women become pregnant: at what age is a woman too old to become a mother?

Most of us might agree that a 25 year old woman is young enough to receive help, but that a 70 year old is too old. However, drawing the cut-off line at some point between these extremes is not easy. With the help of in vitro fertilization and donated oocytes, women like Maria can become pregnant at an age where nature would naturally prevent the possibility of conceiving. Typically, women run out of oocytes in their early 50’s and without oocytes and the granulosa cells that surround them, they lose their ability to make estrogen. This natural process, called menopause, can happen earlier or later for a given individual, but the ability to get pregnant and deliver a healthy baby declines rapidly for women in their late 30’s and on into their 40’s. The age of the woman is a determining factor of her since a 40 year old woman is trying to get pregnant with a 40 year old oocyte, and these older oocytes don’t perform well. For example, the older oocyte is not good at keeping track of its own DNA, as evidenced by the increasing incidence of genetic defects such as Down syndrome in older mothers. And as if this wasn’t bad enough, the rate at which oocytes are lost from the ovaries (also know as a woman’s biological clock) doubles at about age 38. If this doubling didn’t happen, we think that women wouldn’t reach menopause until their early 70’s. It is thought that the speeding up of the biological clock in the late 30’s is nature’s way of clearing out the remaining oocytes, so that women lose their ability to become pregnant but are then around to raise the children that they already have.

Based on nature’s model, we might consider limiting IVF treatment to women that are in their early forties or younger. But with donated oocytes, this limit can be pushed and there are no legal age limits for pregnancy. So, who gets to decide when it’s too late to become pregnant? As far as following “nature’s model”, is age different than other factors that lead to infertility? Do we make rules? And do the rules apply to men too, where nature doesn’t have limits?

Note: Pacific Fertility Center does have both lower and upper age limits in place.

News broke earlier today about the death of a 69 year old mother who had undergone fertility treatment at age 66. She gave birth to twins in December 2006.

This is a very unfortunate incident and we express condolences to the loved ones, especially the children who are left behind. However, it is necessary to clarify that Pacific Fertility Center was not involved in the treatment of this patient. The AP article printed the name of the clinic as “Pacific Fertility Center”, which is an error of ambiguity since there are two fertility clinics with similar names. The fertility clinic where this woman received services was Pacific Fertility Center-Los Angeles. Our center, which is located in San Francisco, has no affiliation with the clinic in Los Angeles. While our names are similar, our standards of practicing medicine are much different. To begin, here at Pacific Fertility Center in San Francisco, it is standard procedure to verify the identity and age of the persons being treated at every visit.  Our physicians would not have treated a woman at the age of 66, since we believe this to be unethical. At Pacific Fertility Center in San Francisco, we believe it is our foremost and ethical responsibility to assure the children that are a result of our services are provided loving and caring families.

At Pacific Fertility Center, we consider very carefully the number of embryos we transfer to each patient. Our goal is to create a healthy singleton pregnancy. We do our best to avoid multiple gestations. Consequently, in many cycles where we think that the chance of pregnancy is extremely high, we transfer only a single embryo. Our outstanding and robust embryo cryopreservation program preserves all embryos that were not transferred in the fresh cycle. Patients who transfer only a single embryo can feel secure in knowing that there are frozen embryo(s) available should they be needed.

Recently, we completed our analysis of the cumulative pregnancy rates per cycle for 2007. This type of report represents the overall pregnancy chance from a single IVF treatment cycle. This data was not available previously as many patients delay their use of frozen embryos. This cumulative analysis looks at the chance of pregnancy from a single IVF cycle when using both fresh embryos and subsequent frozen embryos, if needed.

Table 1 shows the rates for patients that used their own eggs (oocytes).
Table 2 shows pregnancy rates for patients that were the recipients of donor oocytes.

Please note that these are not delivered pregnancy rates. Many of these pregnancies are ongoing. There are also some patients that have not yet achieved pregnancy, but have frozen embryos remaining.

Question: I’m 38 years old and have been trying to get pregnant for about a year. All of my lab tests and my husband’s semen analysis have been normal. What do you think is the problem?

Answer: For women in their late 30s, it is naturally going to take longer to get pregnant. They are experiencing what I like to call “age-related sub-fertility.” Some may be lucky and become pregnant right away. However, for the majority of women, as we age fewer of the eggs we ovulate are chromosomally normal; and therefore fewer ovulations result in the release of a normal egg. It just may take more ovulations before that normal egg is released, fertilized, implants, and succeeds in becoming a baby. It is estimated that about 1 in 5 eggs are normal at age 35, about 1 in 10 at age 40, and only 1 in 25 at age 45. So, at age 38, if about 1 in 8 eggs are normal, you may have only 1 or 2 chances a year for successful conception. If your intercourse was not well-timed that cycle or there was some other subtle inefficiency, the chance for conception may be lost. The catch-22 with age-related sub-fertility is that it takes longer to get pregnant and meanwhile, you are getting older and your egg quality is also declining. For this reason, many women seek treatment with fertility medications or IVF as they get older. These treatments can increase the number of eggs produced and exposed to sperm in a single month, thus improving the odds that normal eggs will be found. The good news is that for most women still in their 30s, fertility treatments for age-related sub-fertility are often successful.

– Carolyn Givens, M.D.

We never planned nor expected to have twins, but we feel exceptionally fortunate to have the best of both worlds: a boy and a girl. It was a great hand of luck, which, minus the infertility part, has been our story from the beginning of this journey.

We knew we wanted kiddos, but like many couples wanting kids nowadays, we thought we had a good reason to postpone starting a family. Our plans were to travel the world, come back home and then grow kids. We sold everything we owned, bought two motorcycles and traveled across 30 countries over the span of three years before returning to San Francisco. Only later did we discover that infertility would be our issue.

We tried to conceive on our own for a year without luck. When we decided to get preliminary blood work to help solve our mystery, each test came back normal. Our prognosis wasn’t good: unexplained infertility.

I spent the next three weeks researching our fertility options online—looking at doctors and clinics, and comparing their success rates and patient reviews. During my research process, I learned how quickly the chances of having a family were dwindling for a couple of our age. A 40 year old healthy woman has around a 25% chance of a live birth through IVF. While a woman over 42 years of age, has a 5% or less chance of conceiving. I was almost 41 years old.

I felt very good about Pacific Fertility Center as all five of the doctors were researchers in the field of fertility with exceptional resumes. Furthermore, as practitioners, they seemed more experienced than most, in working with women past age 40. I chose the first doctor I spoke with, Doctor Ryan, based on her online profile. She was straightforward, and took the time to explain our treatment to us both verbally and visually (drawing out diagrams). She has a rare ability to conduct a professional yet personal relationship. She is genuinely warm, personable, and interested in her patients. Pierre and I knew after one meeting that we wanted to work with her.

The injections and the medications became a kind of ritual for us. The experience brought Pierre and I closer. Of the seven eggs collected, four developed into embryos. On the third day, all four were transferred and we started to wait, hopeful it would “work”. Six weeks later, late in the evening, I began to bleed and was sure I had miscarried. For the first time I realized what it meant to me to have a child. I wouldn’t let myself believe I had miscarried, but I also recognized the emotional tail-spin I’d go into if I had in fact lost the pregnancy. We both must have had the saddest night of our lives. Early the next morning, I went in for an emergency appointment. The image came up on the ultrasound screen and, within seconds, the doctor turned to me and exclaimed: “You have twins!” Pierre and I looked at each other elated. Twins! It was the best fortune imaginable.

Max and Emmanuelle are now 9 months old. We barely remember life before them. They are healthy, incredibly good-natured babies. Pacific Fertility Center was the best choice for us, but not entirely based on our (and Dr Ryan’s!) success. We knew it was a one-shot deal and the result, a girl and a boy, could not have been better.

For parents thinking about using IVF, I would recommend setting a limit in the number of attempts before you begin treatment. Knowing we were with the best doctors allowed us to approach the procedure in a more relaxed way. Knowing our odds, however, we did feel like this was our last hope. Now we find it more amusing and gratifying to find ourselves looking for our own characteristics in our kids. We see Max and Emmanuelle as little individuals who have been placed into our care, two beautiful and unique little people whose personas are going to blossom in front of our eyes.

We are incredibly grateful to Dr. Ryan and the team at PFC for allowing us to know the joy of giving birth. However, we are most grateful to be parents. Above all else, it is this unconditional love that lasts 18 years and beyond, that really defines parenthood. Even if your fertility issue doesn’t permit the use of your own genes, know that you still will be a very loving, loved and fulfilled parent.

–Submitted by Merritt Grooms

The article in January’s issue of Fertility Flash, Conception at 40 and Beyond – Does IVF Help? contained some errors in the table. The following is a reprint of the article with corrections.

We all know that fertility declines with female age but what is not certain is how much does in vitro fertilization improve one’s chances of conception if a woman/couple is having problems conceiving on their own?

The table below is one I often use when counseling patients 40 and over about their chances of conception with in vitro fertilization.

This table represents pregnancy outcomes with PFC patients from January 2003 to March 2008, so most of the viable pregnancies tabulated here have been delivered.

One thing to note is that over half of the patients that get a positive beta-hCG result do not end up delivering a baby. This is consistent with the observation that most embryos from women 40 and over have abnormal numbers of chromosomes.

Another thing to note is that pregnancies after age 43 are exceedingly rare, even with IVF. We encourage most women over age 43 to strongly consider ovum donation.

World-wide, over half the babies born from assisted reproduction to women over age 40 are born from ovum donation, not from their own eggs.

In southern California last month, a set of octuplets were born via Cesarean section. The mother, Ms. Nadya Suleman, recently divulged that this pregnancy resulted after undergoing in vitro fertilization (IVF) treatment. Most previous cases of high-order multiple births have occurred after treatment with injectable fertility drugs combined with intrauterine insemination (IUI). This case is unusual in that the treatment was IVF, where the number of embryos transferred back to the patient is a conscious decision on the part the patient and her physician. We are reassured to hear that Ms. Suleman and the octuplets are thus far doing well, but certainly the potential complications of premature birth may not present themselves until much later in each of these octuplets’ coming days, months, or even years.

We are very concerned that such an event of a high-order multiple pregnancy has occurred, and would like to reiterate that PFC takes the issue of multiple gestation very seriously. PFC has been taking steps to minimize the risk of multiple pregnancy for several years. Balancing high pregnancy rates with low pregnancy risk improves pregnancy outcomes. Achieving that balance and reducing the risk of multiple pregnancy is our goal. In all treatment cycles that we perform here at PFC, our ultimate aim, and any recommendations we provide, are with the hope of achieving a singleton pregnancy- the safest pregnancy.

Fertility physicians are very aware that one of the most important side effects of fertility treatment is multiple gestation. Our governing organization, the American Society of Reproductive Medicine (ASRM), as well as the Society for Assisted Reproductive Technology (SART) have worked steadily to formulate evidence-based guidelines for the number of embryos to be transferred in assisted reproductive technology (ART) cycles. These guidelines were first established in 1996 and were updated in 2006 to reflect improved success rates with ART. Over the past decade we have seen a significant decrease in the number of high-order multiples in the US.

We at PFC adhere to the ASRM and SART guidelines. These guidelines provide the flexibility to give each patient treatment individualized to her needs, and her best chance to become pregnant; while minimizing the risks of a high-order multiple pregnancy.

SART member clinics are committed to following these guidelines, although it would appear that the guidelines were not followed in Ms. Suleman’s case.

Pacific Fertility Center is pleased to share our delivered pregnancy rates for 2007 and our preliminary clinical pregnancy rates for 2008. These outstanding pregnancy rates are made possible thanks to our team of board certified Reproductive Endocrinology and Infertility specialists, as well as, our highly trained embryologists.

Clinical pregnancy reflects the finding of a pregnancy sac in the uterus following transfer. Delivered pregnancy rate will be lower after accounting for miscarriage and pregnancy loss, particularly in older age groups.

Pacific Fertility Center Preliminary Clinical Pregnancy Rates for 2008

Delivered Pregnancy Rates 2007 (as reported to SART and CDC)

We all know that fertility declines with female age, but what is not certain is how much in vitro fertilization (IVF) improves one’s chances of conception if a couple/woman is having problems conceiving on her own.

The table below is one I often use when counseling patients 40 and over about their chances of conception with in vitro fertilization.

This table represents pregnancy outcomes with PFC patients from January 2003 to March 2008, so most of the viable pregnancies tabulated here have been delivered.

One thing to note is that over half of the patients that get a positive beta-hCG result do not end up delivering a baby. This is consistent with the observation that most embryos from women 40 and over have abnormal numbers of chromosomes.

Another thing to be aware of is that pregnancies after age 43 are exceedingly rare, even with IVF. We encourage most women over age 43 to strongly consider ovum donation.
World-wide, over half the babies born from assisted reproduction to women over age 40 are born from ovum donation, not from their own eggs.