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mercredi 13 avril 2011

Question 49. Are the children born after IVF normal?

Posted on 06:31 by Unknown
The goal of all of our patients is to have a normal, healthy child. However, there are risks in life that none of us can eliminate and unfortunately any child can be born with a birth defect. So the real question is whether IVF derived pregnancies result in more complications and birth defects than non-IVF pregnancies. But here's the problem...patients who undergo IVF have a problem....INFERTILITY.

So really what we need to compare are the outcomes of pregnancies in infertile couples that conceived on their own and those that conceived with IVF...otherwise we are truly comparing apples and oranges. One very revealing study looked at pregnancies in gestational carriers (who have proven fertility which is why they were chosen to be gestational carriers in the first place!) and compared these to IVF pregnancies where patients carried themselves. Guess what? All the issues of bleeding, prematurity, low birth weight etc completely went away! So since most infertile patients do not use a gestational carrier, we need to realize that there may not be an easy way to separate out the cause and effect in terms of outcomes as the issue may be related to the patient needing infertility treatment and not necessarily the treatment itself. Twins are the clear exception as twins (at least non-identical twins) can be prevented by sticking with single embryo transfer.

I am proud to report that we have the highest percentage of single embryo transfers in the country. I know that this is true because we perform so much Natural Cycle IVF and 99% of these cycles result in only a single egg and therefore only a single embryo available for transfer.

So after that introduction, let's look at today's Question of the Day. I have included supplemental information that is in the stimulated cycle IVF consent form that we use here at Dominion. This consent form was produced by SART and provided to all US fertility clinics.

Question 49. Are the children born after IVF normal?



The question of the health of children born after advanced fertility treatments is one that has great importance both to patients and fertility physicians alike. In general, the data regarding the outcomes for children born after IVF, either with or without the use of ICSI, have been extremely reassuring.

The problem with these studies is the identification of an appropriate control group with which to compare the rate of problems found in the children conceived with advanced fertility techniques. Overall, most studies suggest a background risk of birth defects in naturally conceived children of approximately 4% to 5%. However, these couples tend to be younger than the couples undergoing IVF and, by definition, do not suffer from infertility. Although the vast majority of studies suggest no increased risk of anomalies in children conceived after IVF, few of these studies have looked at the rate of congenital anomalies in children conceived naturally but born to parents who suffered infertility that spontaneously resolved without treatment. This group of patients clearly represents a more appropriate control group with which to compare with patients who seek out advanced fertility treatments. The few studies that have looked at this question have noted that although patients who suffered from infertility have a higher rate of anomalies and pregnancy related complications, the means by which these couples eventually conceived (spontaneously or with IVF) did not influence the rate of these problems. Therefore it may not be the IVF process per se that is the issue here but rather the underlying infertility that matters.

The following is from the SART stimulated cycle IVF consent form.....

1. Overall risks.

Since the first birth of an IVF baby in 1978, more than 4 million children have been born worldwide following IVF treatments. Numerous studies have been conducted to assess the overall health of IVF children and the majority of studies on the safety of IVF have been reassuring. As more time has passed and the dataset has enlarged, some studies have raised doubts about the equivalence of risks for IVF babies as compared to naturally conceived babies.

A major problem in interpreting the data arises from the fact that comparing a group of infertile couples to a group of normally fertile couples is not the proper comparison to make if one wants to assess the risk that IVF technology engenders. Infertile couples, by definition, do not have normal reproductive function and might be expected to have babies with more abnormalities than a group of normally fertile couples. This said, even if the studies suggesting an increased risk to babies born after IVF prove to be true, the absolute risk of any abnormal outcome appears to be small. Singletons conceived with IVF tend to be born slightly earlier than naturally conceived babies (39.1 weeks as compared to 39.5 weeks). IVF twins are not born earlier or later than naturally conceived twins. The risk of a singleton IVF conceived baby being born with a birth weight under 5 pounds nine ounces (2500 grams) is 12.5% vs. 7% in naturally conceived singletons.

2. Birth Defects.

The risk of birth defects in the normal population is 2-3 %. In IVF babies the birth defect rate may be 2.6-3.9%. The difference is seen predominately in singleton males. Studies to date have not been large enough to prove a link between IVF treatment and specific types of birth defects.

Imprinting Disorders. These are rare disorders having to do with whether a maternal or paternal gene is inappropriately expressed. In two studies approximately 4% of children with the imprinting disorder called Beckwith-Weidemann Syndrome were born after IVF, which is more than expected. A large Danish study however found no increased risk of imprinting disorders in children conceived with the assistance of IVF. Since the incidence of this syndrome in the general population is 1/15,000, even if there is a 2 to 5-fold increase to 2-5/15,000, this absolute risk is very low.

Childhood cancers. Most studies have not reported an increased risk with the exception of retinoblastoma: In one study in the Netherlands, five cases were reported after IVF treatment which is 5 to 7 times more than expected.

Infant Development. In general, studies of long-term developmental outcomes have been reassuring so far; most children are doing well. However, these studies are difficult to do and suffer from limitations. A more recent study with better methodology reports an increased risk of cerebral palsy (3.7 fold) and developmental delay (4 fold), but most of this stemmed from the prematurity and low birth weight that was a consequence of multiple pregnancy.

Potential Risks in Singleton IVF Pregnancies




In this table, the Absolute risk is the percent of IVF Pregnancies in which the risk occurred. The Relative Risk is the risk in IVF versus the risk in non-IVF pregnancies; for example, a relative risk of 2.0 indicates that twice as many IVF pregnancies experience this risk as compared to non-IVF pregnancies. The numbers in parentheses (called the “Confidence Interval”) indicate the range in which the actual Relative Risk lies.

3. Risks of a Multiple Pregnancy

The most important maternal complications associated with multiple gestation are preterm labor and delivery, pre-eclampsia, and gestational diabetes (see prior section on Risks to Woman). Others include gall bladder problems, skin problems, excess weight gain, anemia, excessive nausea and vomiting, and exacerbation of pregnancy-associated gastrointestinal symptoms including reflux and constipation. Chronic back pain, intermittent heartburn, postpartum laxity of the abdominal wall, and umbilical hernias also can occur. Triplets and above increase the risk to the mother of more significant complications including post-partum hemorrhage and transfusion.

Prematurity accounts for most of the excess perinatal morbidity and mortality associated with multiple gestations. Moreover, IVF pregnancies are associated with an increased risk of prematurity, independent of maternal age and fetal numbers. Fetal growth problems and discordant growth among the fetuses also result in perinatal morbidity and mortality. Multifetal pregnancy reduction (where one or more fetuses are selectively terminated) reduces, but does not eliminate, the risk of these complications.

Fetal death rates for singleton, twin, and triplet pregnancies are 4.3 per 1,000, 15.5 per 1,000, and 21 per 1,000, respectively. The death of one or more fetuses in a multiple gestation (vanishing twin) is more common in the first trimester and may be observed in up to 25% of pregnancies after IVF. Loss of a fetus in the first trimester is unlikely to adversely affect the surviving fetus or mother. No excess perinatal or maternal morbidity has been described resulting from a “vanishing” embryo.

Demise of a single fetus in a twin pregnancy after the first trimester is more common when they share a placenta, ranging in incidence from 0.5% to 6.8%, and may cause harm to the remaining fetus. Multiple fetuses (including twins) that share the same placenta have additional risks. Twin-twin transfusion syndrome in which there is an imbalance of circulation between the fetuses may occur in up to 20% of twins sharing a placenta. Excess or insufficient amniotic fluid may result from twin-to-twin transfusion syndrome. Twins sharing the same placenta have a higher frequency of birth defects compared to pregnancies having two placentas. Twins sharing the same placenta appear to occur more frequently after blastocyst transfer.

Placenta previa and vasa previa are more common complications in multiple gestations. Abruptio placenta also is more common and postpartum hemorrhage may complicate 12% of multifetal deliveries. Consequences of multiple gestations include the major sequelae of prematurity (cerebral palsy, retinopathy of prematurity, and chronic lung disease) as well as those of fetal growth restriction (polycythemia, hypoglycemia, necrotizing enterocolitis). It is unclear to what extent multiple gestations themselves affect neuro-behavioral development in the absence of these complications. Rearing of twins and high-order multiples may generate physical, emotional, and financial stresses, and the incidence of maternal depression and anxiety is increased in women raising multiples. At midchildhood, prematurely born offspring from multiple gestations have lower IQ scores, and multiple birth children have an increase in behavioral problems compared with singletons. It is not clear to what extent these risks are affected by IVF per se.
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lundi 11 avril 2011

Question 48. How successful is IVF?

Posted on 11:15 by Unknown
Different physicians have different styles. I have always attempted to involve my patient's in the decision making process so that they look upon the treatment plan as their plan not my plan. Not all patients want this responsibility. Some look to the physician to run the show with little to no input. I always try to make my recommendation clear but I think that there are often alternative pathways.

For the past 4 years we have been promoting Natural Cycle IVF as an alternative pathway to traditional IVF. I believe that many clinics are unable to offer this approach effectively because of cost limitations and volume concerns. However, it certainly represents more of a finesse approach than that of stimulated cycle IVF. On the other hand, no arguing that stimulated cycle IVF has a higher pregnancy rate per initiated cycle and a low cancellation rate. On the other other hand, some patients are willing to trade off the cancellation rate in order to avoid taking fertility drugs....and so on...

So here is today's Question of the Day from the 2nd Edition of 100 Questions and Answers about Infertility. We are almost halfway there!


48. How successful is IVF?

Overall, the success rates for IVF have improved markedly since 1978 (when Louise Brown was conceived), but success rates vary widely depending on the couple’s infertility factors and the clinic performing the IVF procedure. Success rates for U.S. IVF clinics are published on the CDC’s website (www.cdc.gov/ART/index.htm). The standardization of clinic success rates evolved from 1994 passage of the Fertility Clinic Success Rate and Certification Act (the so-called Wyden law), which seeks to protect U.S. consumers from inflated IVF success rates.

Importantly, many subtleties influence clinic-specific IVF pregnancy rates, including patient selection bias (that is, some clinics tend to treat tougher cases, so their success rates might be lower than those of clinics that take only routine cases). The paucity of clinics that offer Natural Cycle IVF is likely related to this reporting requirement. Natural cycle IVF can be an effective fertility treatment but the pregnancy rate will be less than for stimulated cycle IVF and the number of cancelled cycles will also be higher as patients may ovulate before egg collection, or fail to fertilize or fail to have a viable embryo to transfer.

Unfortunately, at the present time all IVF cycles are reported the same way with the CDC failing to segregate results from Natural Cycle IVF from stimulated cycle IVF. Needless to say, this reporting method does not encourage clinics to offer Natural Cycle IVF as the apparent IVF success rate will be reduced by the inclusion of Natural Cycle IVF in the calculations.

Table A: Factors influencing IVF success rates

1. Patient’s age
2. Type of infertility diagnosis
3. Duration of infertility (Best prognosis if <5yrs)
4. Experience/expertise of the clinic
5. Number of embryos transferred
6. Type of IVF performed: Stimulated vs. Natural Cycle IVF

For women younger than 34 years of age, most will achieve pregnancy within one to three treatment cycles; indeed, many succeed in their first attempt. For women older than 35 years, the success rates tend to decrease simply because the aging process affects the quality of these women’s eggs. For a detailed discussion of IVF success rates, couples should visit the website for the clinic where they are considering treatment. They should also discuss their specific likelihood of success with their reproductive endocrinologist. IVF pregnancy rates do vary by clinic, so patients should carefully scrutinize their chances for success at the particular clinic rendering treatment.
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jeudi 7 avril 2011

Question 47. How do I know if I need IVF?

Posted on 08:12 by Unknown
Although there are many paths to reproductive success, IVF is usually the fastest road to success. However, not all patients are thrilled about taking that road as the use of stimulation drugs can be intimidating to say the least. Our extensive experience in Natural Cycle IVF has been so encouraging that it makes one reassess how to counsel patients who are considering other options such as clomid/IUI or gonadotropin/IUI treatment cycles. Although our initial inclination was to encourage Natural Cycle IVF mainly in patients < 35 years old with well-defined fertility issues, our results suggest that success can be obtained in older patients and in those with unexplained infertility. Clearly pregnancy rates will be higher in patients < 40 years old but our current record holder was 47 years old with 4 failed stimulated cycle IVF attempts prior to achieving an ongoing pregnancy with Natural Cycle IVF. Go figure.

I spent over an hour on the phone with a reporter from NPR recently. She was very interested in Natural Cycle IVF and was considering running a piece on the topic. However, after speaking with some other local REs who were totally dismissive of Natural Cycle IVF she stopped answering my emails. Sad but true....good news doesn't sell papers or get listeners to stick with one radio station....and we believe that Natural Cycle IVF is very good news indeed!

So although the smug answer to the Question of the Day is that everyone needs IVF...they just don't know it yet.....here is a more balanced view.

47. How do I know if I need IVF?

Not all patients need IVF or are good candidates for IVF. Thus the answer to this question can be determined only after you undergo a comprehensive infertility evaluation by your reproductive endocrinologist. Nevertheless, some situations clearly require the use of IVF. For example, women with absent or severely damaged fallopian tubes should be treated immediately with IVF. Likewise, IVF should be performed first if the male partner has very poor sperm quality. For other patients, the use of IVF may be less clear-cut, especially given that many different treatment options exist. In such cases, the doctor should discuss with the couple the pros and cons of each option, and then all parties should jointly decide on a treatment plan.
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