The Right To Know: use of laparoscopy to help diagnose unexplained infertility

One of the most challenging aspects of infertility care is helping couples understand why they have not yet become pregnant. About 20-30% of couples will have no definitive diagnosis after completing a standard infertility evaluation[r1] .  In today’s fast-paced treatment paradigm, some patients prefer to move forward with treatment without further clarification. Although oftentimes appropriate, this strategy should not be applied to every patient/couple. Laparoscopy and hysteroscopy are minimally invasive, out-patient surgeries [r2] that can provide a diagnosis and sometimes even offer improved pregnancy rates if scar tissue or endometriosis is found and treated at the time of surgery.

Women with infertility are about eight times more likely to have endometriosis than women that have been pregnant. Treatment of endometriosis can not only reduce pain but also improve pregnancy rates as well. In fact, a large, randomized meta-analysis[r3]  of the available research found that treating endometriosis was associated with about a 60% increase in the chance for a successful pregnancy. Additionally, if there is scar tissue preventing the egg from reaching the fallopian tubes this can also be identified and treated. So consideration of diagnostic surgical procedures can be beneficial. The challenge is in deciding which patients should pursue this option further.

A more recent study [r4] investigated the usefulness of these diagnostic surgical procedures from a financial perspective. They found that laparoscopy was cost-effective in improving pregnancy rates/outcomes based upon many factors including the potential impact of endometriosis. Finally, they also found that undergoing diagnostic surgery was associated with a lower rate of patients “dropping out” of fertility treatment before becoming pregnant. This suggests that having all of the information available prior to treatment is preferred by some couples experiencing infertility. In summary, if you are having trouble conceiving and want more information, minimally invasive surgery may be your best next step.

Robert Greene, MD, FACOG

CNY Fertility Center

e-mail me at rgreene@cnyfertility.com

Call our toll-free number at 800.539.9870 or request a consult here.

Potential Benefits of FET: why more IVF patients should consider FROZEN over FRESH embryo transfer

One of the most common questions infertility patients going through Advanced Reproductive Treatments (ART) ask is: “will freezing embryos reduce my chance at a pregnancy?”  During the first decade and a half of IVF treatment, there was a much lower success rate through Frozen Embryo Transfer (FET). In a recent post, I summarized how the newer technique of “vitrification[r1] ” helped overcome the potential impact of cryotherapy upon embryo quality. And in a separate post[r2] , I described the importance of properly preparing a woman’s uterus prior to placing an embryo. Newer data is showing that due to these combined factors some patients can actually see an improvement in their pregnancy rate by deferring transfer of their embryos from a “fresh cycle” to an FET.

It has long been noted that the highest pregnancy rates are achieved when using an egg donor. Although it has often been assumed that this is due to improved embryo quality, newer data is showing that endometrial receptivity may also be a factor. The largest review to date [r3] recently combined the results of 64 clinical research studies—including 3 randomized trials. They found that freezing embryos and transferring them in a later cycle was associated with about a 30% increase in pregnancy rate. There was no difference in the rate of miscarriage; further reassuring that the process of freezing/thawing embryos maintained their health and viability.

Another important benefit of a freeze-all (or “staggered”) cycle is that it substantially reduces a woman’s risk of ovarian hyperstimulation syndrome (OHSS). So when considering your treatment options with your provider it might be worth considering the potential benefit of creating embryos now that you plan to actually transfer later.

Robert Greene, MD, FACOG

 

BIRTH SPACING and Secondary Infertility **

Timing may be important for couples experiencing secondary infertility. “Birth spacing” refers to planning the ideal interval between pregnancies. Along with thinking about how far apart you want your kids to be in age, you need to think about hormone balance. It takes time after childbirth for your nutritional status to improve enough to support another pregnancy. It takes time for your body to reestablish hormone balance as well. But if you wait too long, your reproductive hormones may fall out of balance. A recent analysis of 67 studies looking at the outcomes of more than 11 million pregnancies demonstrated that the ideal interval between pregnancies is between 18 months and 6 years. Waiting fewer than 18 months resulted in a much higher chance of preterm birth or having a baby with low birth weight. Women that waited less than 6 months also had a higher risk of miscarriage. Couples, especially those who remarry, might want to keep the 6 year mark in mind when planning to expand their family together.

From PERFECT HORMONE BALANCE FOR FERTILITY[u1] : Book Excerpt: P. 16

IVF Success Rates Hit All Time High—but repetition is often the key ingredient to achieving pregnancy

The latest review of the pregnancy rate achieved through advanced reproductive techniques (ART) like in vitro fertilization (IVF) is the most encouraging ever. One press release read “Success of Fertility Treatment May Approach Natural Birth Rate.” Considering that many couples that need IVF have no other treatment options; this is an extremely encouraging revelation. Since the first successful IVF pregnancy was achieved in 1977 (resulting in the birth of Louise Brown in July 1978); it is estimated that 5 million babies have been born through this technology[r1] ! With the success rate and the need for treatment increasing, it is important that we consider what else we can do meet the needs of even more couples.

Here is what we now know. Even the most fertile couples have a natural fertility rate of about 20% for any given month. Their ultimate success is achieved through repetition; if not successful one month they can try next month, and the month after that until they are successful. Observation shows that they typically achieve a pregnancy rate of 65% within 6 months and 80% within a year. By contrast, couples that need fertility treatment have to pay for each cycle that they are attempting to conceive which often limits their effort to one or two attempts. New data shows that with persistence, infertile couples can achieve success rates that are as good or better than people that are considered fertile.

Specifically, the New England Journal of Medicine published data summarizing the results of nearly a quarter of a million women[r2]  treated at centers throughout the USA. This is the best estimate of the average success since it does not reflect a specific group of women or the experience of one specific IVF center. What they found was very hopeful. Nearly 60% of the women that were undergoing treatment had a baby (live birth). In fact, 30% of the women that underwent ART had a baby following their first IVF attempt! The majority of those not successful on their first attempt; did achieve a success rate as high as or higher than those of fertile patients the same age. In other words, IVF is able to overcome most obstacles to achieving a successful pregnancy except those related to age and its impact upon egg quality. Even though live birth rates were lower when older women used their own eggs; the same study found a cumulative live birth rate of 60-80% when women used an egg donor—regardless of the age of the woman carrying the pregnancy and delivering the baby.

Other studies released the same week [r3] demonstrated that women that were experiencing anxiety or depression before IVF did not have a lower chance for achieving a pregnancy. However, they did find that a failed IVF cycle can exacerbate these problems. This further emphasizes the need to focus on the success rates achieved with repeat IVF cycles. Currently there are about 1.5 million ART cycles being performed globally each year resulting in the birth of about 350,000 new babies. The key to focus on is that success rates are very high but it can take up to 6 IVF attempts for couples with more complicated problems to actually have a baby. Clearly the path to parenthood for couples that need ART is repetition. That is why it is so important to make treatment accessible. Personally, I am proud to work at a center that offers treatment at the most competitive prices [r4] in order to make IVF treatment accessible to all of those that need/want it.

Robert Greene, MD, FACOG

CNY Fertility Center

e-mail me at rgreene@cnyfertility.com

Call our toll-free number at 800.539.9870 or request a consult here.

Bed rest following Embryo Transfer–time to revise an out-dated recommendation

Traditionally, bed rest has been recommended for women after any medical procedure. For instance, after delivery of a baby, women were prescribed 6 weeks of bed rest until it was ultimately proven that that inactivity increased their risk of DVT (blood clots in the deep veins). Even though bed rest had been encouraged with good intentions; it did not result in the best outcome. Nonetheless, it is challenging to reverse widely accepted but unhelpful advice. Now that IVF has been around for over 3 decades, it is time to review how we advise patients going through treatment and reconsider whether bed rest is still advisable.

In the early days of IVF, women were restricted to bed rest for 2 weeks after an embryo transfer. In fact, patients were not even allowed to stand up for quite some time after the procedure. Instead they were transported to a hospital gurney and relocated to a hospital bed—even using a bedpan when required instead of going to the toilet. It gradually became apparent that such severe limitation wasn’t needed. Back in 1997, the first study [r1] appeared suggesting that even a 24 hour period of bed rest was unnecessary. Specifically they demonstrated that even when patients were only limited to 20 minutes of activity restriction; pregnancy rates were comparable.

Subsequently, in 2005 a much larger [r2] and well designed study found that when patients were allowed to get up immediately after their embryos were placed; their pregnancy rates were as good as patients that were asked to lie flat for an hour.  Finally, a 2011 review [r3] of all of the published research on this subject confirmed that there is no advantage to bed rest and instead that there may be a disadvantage to being totally sedentary. This isn’t surprising since inactivity combined with high levels of estrogen can promote blood clot formation as well as a rise in insulin resistance. By contrast, exercise reduces inflammation, lowers stress hormone levels and promotes healthy blood flow.

During pregnancy there has also been a reversal of the popular myth that exercise should be limited. In 2008, the US Department of Health and Human Services issued comprehensive guidelines that healthy women should begin or continue aerobic exercise of moderate intensity during pregnancy. In fact, it was confirmed in a well designed study [r4] that both mother and baby benefit from aerobic work outs. Despite the research, it is difficult to dispel advice from popular culture. It was even found in one study [r5]  that when IVF patients were advised by their doctors to remain active; most still restricted their daily activity. So as we look for ways to further boost our pregnancy rates and improve the health of the pregnancies that result it is important that we constantly re-evaluate how we guide women following IVF.

IVF with hGH: time to reconsider an under-used treatment option

One of the greatest challenges that we face in treating couples with infertility, is what options to offer beyond the typical treatment protocols. Clearly, most of our patients are well served with the basic ovarian stimulation methods but in some patients that may exacerbate or simply ignore an underlying hormone imbalance that’s compromising success rates. Therefore, one of the greatest challenges is to figure out how and when to tweak the typical combination of meds in order to shift the hormone balance back to a more favorable outcome. This is the reason that we should now reconsider the use of human growth hormone (hGH) for patients that have failed previous IVF treatment.

I trained under Dr. David Meldrum at UCLA-Harbor Medical Center in Los Angeles. Back in the early 1990’s he was advocating the consideration of adding hGH to the protocol of certain patients. His reasoning was good. First of all, we know from previous research [u1] that healthy developing eggs produce a growth hormone analogue known as IGF-2.  Better still, other studies [u2] have demonstrated that hGH could possibly increase the ability of eggs to repair damaged DNA. Finally, several studies have found that growth hormone can improve the response of the ovaries to stimulation during an IVF cycle. Given that all of this information has been available for quite some time, it may be surprising to a patient that there hasn’t been wider use of hGH during IVF treatment. Recently, Dr. Meldrum and several other experts [u3] suggested that this was because there remained too much confusion amongst specialists on which patients would benefit from the use of this somewhat expensive but also possibly game-changing hormone.

The good news is that recent studies [u4] have more carefully defined the characteristics of the patients that were receiving hGH. As a result, we have some new data to better guide us as to which women may be most likely to benefit from hGH. Here is a summary of what they found:

  • In women >40 years of age, they found a higher implantation rate and better on-going pregnancy rate in women treated with hGH during ovarian stimulation.
  • In women that are poor responders to ovarian stimulation—defined as three or fewer eggs produced per IVF cycle—there was a marked improvement in pregnancy rate with growth hormone supplementation. They also found an improved outcome in FET cycles from embryos created during these cycles.
  • In women that have poor embryo quality and low pregnancy rate in otherwise encouraging ART cycles, there is not be a clear benefit of using growth hormone. Instead, other causes of poor embryo quality should be explored. Once those have all been addressed, reconsideration of hGH is worthwhile.

Robert Greene, MD, FACOG

CNY Fertility Center

e-mail me at rgreene@cnyfertility.com

Call our toll-free number at 800.539.9870 or request a consult here.

How risky is IVF? It isn’t what the headlines suggest.

 

Once again several news-grabbing studies were reported that sent frightened fertility patients to Google in search of more information. Fortunately, the facts rarely warrant the headlines that are used to drive you to use search engines. Most news items are written by journalists whose goal is to get you motivated to read their piece. Then they try to simplify complex issues that they often do not understand. As a result, you’ll often find that the statistics are described in ways that have been exaggerated to promote more interest than is warranted. Here are several recent examples:

  • “Birth Defects more Common in IVF babies”—was the title of a recent press report[u1] . The statement was based upon a review [u2] of 46 studies which suggested a “37% increase in birth defects” detected following advanced fertility treatment. The baseline incidence of birth defects is 3 of every 100 live births. If this information is accurate, it may actually be due to the fact that women that undergo IVF are followed more closely by their OB/GYN’s then women that conceive naturally.  The reality is that if there is any true procedure related risk; it is sufficiently small that we are still trying to determine what it is. By the way, even before this “news” was published the ASRM reported [u3] that the “…the risk of birth defects in children conceived naturally is 2-3% whereas the risk of birth defects in children conceived by IVF is estimated to be 2.6-3.9%.”
  • “Common IVF Fertility Drugs Increase Childhood Leukemia Risk[u4] ”—was followed by a statement that children born following IVF were “2.6 times more likely to become ill with acute lympoblastic leukemia (ALL).” Given that the baseline risk of this cancer is 1 in 50,000; it would translate into a change in risk to about 1 in 43,500 children born through IVF. Here again, it is worthwhile to review and research this topic but it is far too soon to make conclusions linking fertility treatment to cancer; especially since this study only involved patients in one country (France) and therefore may reflect some local environmental effect. Considering that the recent findings [u5] from the World Health Organization listed the incidence of ALL in France to be among the highest in the European region, this headline did not seem appropriately vetted.
  • “Higher risk of Birth Defects from Assisted Reproduction, Study Suggests[r6] ”—was the press release of a large study just reported in the prestigious New England Journal of Medicine. This was despite the study author’s own conclusion [r7] that “The increased risk of birth defects associated with IVF was no longer significant after adjustment for parental factors.” In other words, when they analyzed the largest data base available to date of women that conceived naturally vs. those that became pregnant through IVF they found a slightly higher risk of birth defects in women that had infertility—even when they became pregnant naturally. Therefore, doctors should continue to counsel couples that have trouble conceiving that they may be at higher risk of having a child with an abnormality; so careful monitoring of their pregnancy is recommended. Not as shocking a conclusion but that was also the position statement [r8] of the American Society for Reproductive Medicine and the Society for Advanced Reproductive Techniques.

In summary, it is worthwhile for patients and potential patients to make every effort to remain informed of the latest research. But rather than believe the sound bite; talk to your doctor about whether or not the study that you read about is accurate, current and actually applies to you.