Could Ovarian Stem Cells Help Older Women Become Pregnant?

Contrary to more than a half a century of scientific belief that women will never have more eggs than the number they are born with, new research says that stem cells in the ovaries may be actually capable of creating new eggs later on in life.

 

This development could be the key to achieving pregnancy older women, who no longer have enough eggs to reproduce.

 

According to the study, published today in the journal Nature Medicine, researchers from Massachusetts General Hospital used stem cells discovered in the ovaries of Japanese women to effectively create healthy human egg cells.

 

“This is a beginning of perhaps something that could bring in new opportunities,” told Dr. Avner Hershlag, chief of the Center for Human Reproduction in Manhasset, N.Y. to Health Day.

 

Up until now it has been believed that women are born with a set number of eggs, which slowly decreases with age. By the time may women reach 35 years of age the supply is diminished enough to create difficulties becoming pregnant. Therefore, getting pregnant at 45 with a woman’s own eggs, or in some desired cases at age 50 or more, presents a significant challenge.

 

Although this research is promising, experts say that it is still a long way off before we know if these eggs grown from stem cells will actually be healthy enough to create human babies. Furthermore, the cells used in this study were collected from women in their 20′s, not from older women who are usually the age group seeking infertility treatment.

 

“Detection of stem cells in ovaries of young women does not necessarily mean that such stem cells can also be found in ovaries of older women,” Dr. Norbert Gleicher of the CHR in New York point out. However, he added, “in a more optimistic interpretation of this study’s results, one can, however, also conclude that presence of these stem cells opens tremendous new opportunities for research and potential clinical applications in women with aging ovaries.”

IVF Success Rates Not Improved by Preimplantation Genetic Screening, According to CHR Research

November 19, 2012 (New York, NY) – There is no evidence that recent technical improvements in preimplantation genetic screening (PGS) improve IVF pregnancy chances, according to a paper just published online in the Journal of Assisted Reproduction and Genetics1. The review, by two fertility specialists from New York’s Center for Human Reproduction (CHR), raises important questions, as this “new” PGS is actively marketed to patients as “proven” and “established” to increase IVF success rates.

In the late ‘90s, PGS was widely utilized in IVF in attempts to improve pregnancy chances. The assumption was it could eliminate genetically abnormal embryos before implantation, thereby raising implantation and pregnancy rates, and reducing miscarriage rates. For a number of years, thousands of women worldwide underwent PGS under this premise, until a number of investigators, including the authors of this new report, demonstrated that, in practice, PGS actually reduced IVF pregnancy rates, at least in older women. By 2008, the American Society of Reproductive Medicine (ASRM) and other authoritative bodies declared PGS ineffective in improving IVF outcomes.

In recent years, a number of important technical improvements were introduced to PGS, which, unquestionably, improved the accuracy of determining chromosomal abnormalities in embryos prior to transfer. Under the assumption that these improvements would finally confirm the widely held opinion that PGS will improve IVF pregnancy rates, a “new” form of PGS is now, once again, aggressively marketed by commercial interests.

After a thorough review of published studies and ongoing registered clinical trials, the paper concludes that there is no evidence that this reintroduction of PGS to IVF improves pregnancy rates. “As we already pointed out in 2008, evidence suggests that the real reason why PGS was ineffective in its first introduction and, likely, remains ineffective in its current reincarnation, is the wrong patient selection, and not the techniques utilized,” explains Norbert Gleicher, MD, Medical Director and Chief Scientist of CHR. “Until we better identify appropriate patient populations for PGS, new techniques are unlikely to benefit patients and, as previously, may actually reduce IVF pregnancy chances.”

“These new techniques, indeed, further complicate considerations about patient selection,” adds David H Barad, MD, Director of Clinical ART and Senior Scientist at CHR. “With the “new” PGS, embryos have to remain in culture for 5-6 days after fertilization, which many embryos of lesser quality do not survive. Some of these embryos would still lead to pregnancy if transferred on day-3, as in routine IVF cycles.” He continues: “Reported higher pregnancy rates with the ‘new’ PGS are misleading because they exclude patients who started IVF cycles but never made it to embryo transfer.”

The paper concludes that the “new” PGS still has to be considered “experimental” and patients should be advised accordingly. “Patients should be aware that PGS is not in any way proven to better pregnancy chances, and may actually do the opposite in some patients,” warns Dr. Gleicher.

1Gleicher N and Barad DH. A review of, and commentary on, the ongoing second clinical introduction of preimplantation genetic screening (PGS) to routine IVF practice. J Assist Reprod Genet 2012; epub ahead of print. (http://link.springer.com/article/10.1007/s10815-012-9871-2/fulltext.html)

Embryo Transfer Numbers: Which is the Correct Choice for You?

The number of embryos that should be transferred during any single IVF cycle is subject to debate.  Some specialists advocate for elective single embryo transfer (or eSET), which signifies – as the name suggests – that women only receive one embryo implantation per IVF cycle.

Others argue that urging women with infertility to use eSET is unethical, as it reduces their pregnancy chances dramatically.  Multiple embryo transfer gives women with infertility a higher chance of conception.

Which is the correct choice?

 

  • Elective single embryo transfer

The argument for single embryo transfer is that it’s considered lower risk.  Multiple embryo transfer is associated with – you guessed it – multiple births. Although the “idea” of twins may seem ideal to couples struggling with infertility, the reality is that multiple births are risky for both mother and baby. There is a higher chance risk of prematurity, handicap and mortality. The mother has increased risk of premature birth, low birth weight, cesarean section, gestational diabetes and pre-eclampsia. As only one embryo is implanted, the couple is not at risk of multiple births.

  • Multiple embryo transfer

The argument against single embryo transfer: it’s considered unethical.

Although transplanting 4 to 5 healthy, good-quality embryos may increase the risk of multiple births in young women not challenged by infertility, the fact is that many women going through IVF do not have good-quality embryos.  As older women have lower-quality embryos, their chances of pregnancy are significantly decreased.  Even if some of the embryos do implant after IVF treatment, their chances of making it through the first trimester are low (miscarriage rates are high in older women). Is it fair for fertility specialists to reduce pregnancy chances in these women, some of whom may just have one chance at IVF treatment?

The correct choice depends on the individual patient.

In this video, Dr. Vitaly A. Kushnir M.D. from Center for Human Reproduction NYC highlights the different factors that drive the decision of embryo numbers – such as the amount of embryos available, quality of the embryos, the woman’s past medical history and  her age.

The current guidelines for embryo transfer are laid out by the American Society for Reproductive Medicine. Keeping in line with Dr. Kushnir’s comments, the ASRM criteria outlines that an important factor in deciding the amount of embryos to transfer is the woman’s age.

For the moment, fertility centers follow the criteria marked out by the American Society for Reproductive Medicine. Don’t be afraid to ask your fertility specialist about the different options available for embryo transfer numbers. Hint: a fertility center giving individualized care will take into consideration your specific case and medical history before deciding which embryo transfer number would be most suited to your treatment.

3 Things Everyone Should Know When Interpreting IVF Success Rates

Annually, infertility clinics are required to report their IVF success rates to the Centers for Disease Control (CDC), and these figures are passed on to the Society for Assisted Reproductive Technology (SART).

Both organizations caution against using this data to measure the effectiveness of treatment in fertility centers because the data can lack reliability and credibility.  In fact, some centers have even been found to manipulate data by finding loopholes in the federally mandated reporting system.

For these reasons, IVF success rates outcomes should be taken with a grain of salt. Unfortunately, people consulting prospective infertility centers continue to consider a clinic’s pregnancy success rates as one of the most important measurements of the quality and level of care that a clinic provides.

Three Things to Keep in Mind When Interpreting a Prospective Clinic’s IVF Success Rates:

1.       Beware of centers with exceptionally high success rates

Chances are these centers have patient exclusion criteria. The reason their success rates are so high is likely because they accept only straightforward infertility cases.

Such centers exclude women who present with symptoms like very high FSH levels, very low AMH levels, a very low follicle count, or simply who are of advanced maternal age (women trying to get pregnant over 40).  By excluding  these women, who have lower pregnancy chances, a fertility center can offer misleading numbers that raise their success rates above industry standards.

So remember, if you’re being treated by or are looking into a fertility center that is claiming astronomical success rates, the rates likely apply only to women with the simplest of infertility cases.

2.  Check before you make your first appointment about “cut-off” values

Before your first appointment, ask if your clinic has any specific cut-off, or exclusion criteria.

You don’t want to settle on a clinic and get started with the consultation and treatment process, only to find out that because of your infertility symptoms they cannot do anything for you.

This is especially true for women of advanced maternal age (35+), as time is of particular importance to these women when trying to get pregnant.

3.  Measure the quality of an IVF center by looking at the pregnancy success rates of its egg-donation program

Experts suggest looking at the pregnancy success rates of a center’s egg-donation program to measure the skill level of a center’s IVF techniques.

Why? Egg donor cycles aren’t affected by the center’s patient selection.

Egg donor programs recruit donors that meet certain criteria, such as being young, healthy and having an excellent ovarian reserve. Therefore, since the reproductive health of the egg donors is more or less uniform, looking at the successful pregnancy outcome rates of the egg donation program is a good way to measure the skill and expertise of an IVF center.

Get some further tips about interpreting IVF success rates in the brief video below.  Fertility specialist Dr. Norbert Gleicher from the Center of Human Reproduction, New York, explains the calculation of IVF success rates and why they vary from clinic to clinic.

 

IVF News: First Baby Born Using New Method of Ovarian Stimulation

Great news for reproductive medicine, as the first baby has been born using a new method of ovarian stimulation for IVF.

UK doctors at Hammersmith Hospital and Imperial College London tested the natural hormone kisspeptin, to stimulate a woman’s ovaries naturally before IVF treatment. This new natural hormal treatment could help women avoid the painful complications of hyperovarian stimulation syndrome (or OHSS) –  a disorder that one in 100 women undergoing IVF will experience.

Prof Richard Fleming of the British Fertility Society stated:

What’s been the conventional treatment for the last 30 years is risky. This looks like another way to make the whole IVF process safer.

Read the full story here

Posted in IVF

New Study Exposes Inaccuracies of the National Reporting System for IVF Success Rates

A new study published in the respected reproductive medicine journal Fertility and Sterility has raised concerns about transparency of the federal reporting system for IVF pregnancy rates.

Researchers from Center of Human Reproduction in New York City found that a number of IVF centers are manipulating IVF success rate reporting in order to artificially inflate their clinic’s pregnancy success rates. Their manipulation of the reporting system has allowed them to gain dramatic economic advantages over properly reporting centers.

Every IVF clinic in the United States is required to report IVF cycle outcomes – both successful and unsuccessful – to the Centers for Disease Control and Prevention (CDC). Many centers report their data to the CDC through the Society for Assisted Reproductive Technologies (SART) voluntary reporting system. These two parallel national data collections are publicly available.

SART and the CDC discourage patients from selecting their IVF clinic solely based on the clinic’s success rates, as looking at this data without considering which types of infertility the clinic specializes in, as well of the age group of their clientele, can be misleading.  Yet, for many people seeking IVF treatment, success rates are a big factor when looking for potential IVF centers.

The researchers examined the national reporting system’s transparency by evaluating the number of IVF centers that were omitting cycles from their annual report. They found that out of 341 clinics, 13 centers failed to report the outcomes of 37.3% of IVF cycles. The bulk of these unreported cycles were of older women, who tend to have a lower chance of becoming pregnant through IVF.

This under-reporting and misrepresenting of IVF success rates not only providing misleading information to prospective patients – it also lead the clinics to increase their share of the U.S. IVF market by as much as 19%. Dr. Norbert Gleicher, MD, the study’s senior author and Medical Director and Chief Scientist at CHR commented:

“We conceived of this study because Senator Wyden, who was instrumental as Congressman in passage of the FCSRCA, recently suggested this national IVF reporting to CDC as a ‘good example’ for other reporting systems that could be implemented throughout medicine under the Affordable Care Act. Our results, of course, suggest otherwise.”

The researchers hope that the publication of their study will shed light on the inaccuracy of the national reporting system for IVF success rates – and hopefully lead to a reform of the SART and CDC reporting requirements.

Read the full report here.

Posted in IVF

Egg donation or donor exploitation?

Fertilization through egg donation began in the 1990’s and was successfully achieved in 1984. Ever since there has been debate surrounding the ethics of egg donation.  As the success rate of fertilization is almost doubled if a donor egg is used, the demand for donor eggs has increased steadily since first discovered.

And the market is competitive, Steinbock (2004) reports couples paying anything from $3,000-$80,000, depending on what positive attributes and talents the donor may have. From IV league education to musical ability couples are willing to pay high price for these precious eggs.

However Steinbock (2004) also reports that although some donors are compensated generously for their eggs they are not given adequate information to help them make an informed decision.  Egg donation takes time and can, in some cases, need follow up medical care. The recipient’s chances of pregnancy increase with the number of oocytes produced by the donor. Yet at the same time this increases the chances of the donor suffering from hyperstimulation syndrome. Often egg donors are not made aware of these complications.

One egg donor NYC reported to the advisory committee New York State Task Force on Life and the Law, that, she was not aware that her donor cycles had been stopped secondary to her developing hyperstimultion syndrome (Steinbock 2004).  As far as she was aware she thought so many eggs had been taken due to the fact that she was very fertile.

Society justifies paying for egg donations, so the women who are unfortunate enough to suffer infertility problems have a choice. However it must be duly noted that there is a growing need to protect the donors. Steinbock (2004) suggests one way to do this is to limit the financial rewards to a fair and reasonable price, as this protects against exploitation of donors as well as financial manipulation of vulnerable couples.

What are the Risks of Egg Donation?

Egg donation, either to an infertile woman, couple, or to an egg donation center, can be an emotionally and financially fulfilling process. However, it can be a difficult process and there are practical considerations that should be taken into account when considering donating eggs.

First of all, strict screening rules and requirements from the start mean that egg donation isn’t possible for every woman. If you pass the initial requirements for egg donation, it is best to be aware of the risks associated with the process before making the decision to donate or not.

Physical Risks: While certain parts during the egg donation cycle may be physically uncomfortable, it’s generally not harmful for the egg donor. However, with most medical procedures, there can be complications. If the donor over-stimulates in response to the fertility medication administered, she may run the risk of Ovarian Hyperstimulation Syndrome (OHSS). OHSS is rare condition that typically occurs in less than 5 percent of egg donors where the production of eggs causing swelling in the ovaries. Severe cases may result in damage to the ovaries, and less severe cases may lead to severe bloating and strong cramping. In addition, bruising, bleeding, or hemorrhaging of the ovary may occur caused by the needle used to retrieve the eggs.

Financial Risks: Although most egg donation programs will pay for the donor’s medical expenses in full, some programs may expect the donor to pay some of the costs herself, through her own insurance or through short-term insurance provided by the program. Before agreeing to anything, it is advised to know up front how much of the cost the program expects a donor to pay. Egg donors should also find out rules of payment, such as whether the program pays for costs if a fertility cycle has to be stopped before eggs are harvested.

Psychological Risks: A 2008 study published in the journal Fertility and Sterility found that approximately one in five egg donors reported lasting psychological effects as a result of egg donation. Some of the feelings were positive – feeling a sense of pride in helping another person or couple, and some were negative – developing concerns about the people who were raising their genetic offspring. Most women find that the process of egg donation is an emotional journey, and sometimes when the motive is entirely based on cash, the donor won’t take all the factors into account.

Time Risks: The egg donation cycle may disrupt a donor’s life more than they initially believed. In addition to self-injections of fertility drugs, egg donors have to visit the doctor for several blood tests and ultrasounds along the way. These appointments must be scheduled around, or interrupt, classes or work hours. Egg donors also have to stop drinking, smoking and having unprotected sex. They may also have to stop taking both nonprescription and prescription drugs. This disruption can lead to stress and emotional exhaustion – but after the process is complete, most egg donors return to their normal daily activities right away. From start to finish, the egg donation process can last up to a few months, depending on the program.

Long-Term Risks: Since egg donation and in vitro fertilization (IVF) have only been used within the past several decades, the long-term health effects of egg donation are unknown, and no long-term studies of egg donors have been performed. The majority of what is known about egg donation risks comes from studies of infertile women who use IVF treatments for assisted reproduction.

Egg donation is a great way to help infertile women and couples start a family. The benefits of egg donation can be rewarding, both financially (about $4,000 per donation) and emotionally, for donors who are healthy and willing to devote their time to the process. That being said, any women interested in becoming an egg donor should know all the facts before starting. It’s advised to look into several programs to learn about the specific procedures, criteria, and support for the donor provided.

New IVF Technique Puts Pregnancy Within Reach for Many 40-somethings

The chance of pregnancy for women in their early 40s who use traditional IVF techniques is approximately 13 percent. However, an in vitro fertilization (IVF) technique known as complete chromosomal screening (CCS) could raise pregnancy success rates to up to 60 percent. CCS could be particularly effective for women experiencing recurrent, unexplained miscarriages.

Through complete chromosomal screening, doctors take the cells of day-old embryos, called blastocysts, and examine them in detail to see if they have exactly 46 chromosomes – 23 from each parent. Aneupliod, or chromosomally abnormal, embryos often end in miscarriage; therefore, by selecting only the normal embryos, the chances of a successful pregnancy increase significantly. In order to reduce chromosomal abnormalities and prevent miscarriage many women also chose to take DHEA supplements during IVF.

After the normal embryos have been selected, they are frozen for a month to give the patient’s reproductive organs time to return to normal post-IVF treatment. This is done because, according to some scientists, embryos can be harmed if put into the womb while in vitro fertilization drugs are still in the patient’s system. Many researchers also claim that cryopreservation produces healthier babies with similar birth weights to those that are conceived naturally. Meanwhile, embryos that are produced by IVF and not frozen tend to produce babies of a lower weight.

Case study

For a study carried out by Colorado researchers, IVF with CCS was performed on 42 women with recurrent miscarriage. Of that group, nine women had only aneupliod embryos, meaning no normal embryos could be transferred. Of the remaining 33 women with at least one chromosomally normal embryo, nearly 88 percent resulted in pregnancy, and only one miscarriage was recorded.

This makes in vitro fertilization with CCS a viable option for women who have tried other IVF techniques with no success.

Will DHEA Help Me Get Pregnant?

DHEA ( or dehydroepiandrosterone) is a hormonal supplement gaining attention and  momentum  in the infertility community as a new treatment that helps improve female egg quality, and consequently can help improve pregnancy rates via IVF.

Is DHEA just another fad treatment, or can it actually help women with infertility get pregnant?

DHEA use

Fertility specialists mainly use DHEA to treat women with diminished ovarian reserve (also known as DOR).  Diminished ovarian reserve is caused by

  • Premature ovarian aging (in younger women)
  • Natural ovarian aging (in older women)

A woman’s ovarian reserve (how well her ovaries produce mature, high quality eggs) naturally declines with age during menopause. Unfortunately some women experience a decline in their ovarian function during their child bearing years – this is known as premature ovarian aging (or POA).

POA affects around 10% of women and it can be detrimental to pregnancy chances. When a woman has POA she will produce lower quality eggs, which leads to the production of lower quality embryos. Lower quality embryos have a lesser chance of successful implantation via IVF and a higher rate of miscarriage, when compared with high quality embryos.

How DHEA affects fertility

The key to treating POA is improving egg quality.

Once female egg quality improves, so will the quality of the embryo – 95% of embryo quality relies on egg quality. This is where DHEA plays its part.

DHEA is important to egg quality as it helps more follicles make it through to the last stage of egg maturation. When a woman has POA, few follicles make it through to this mature stage. At this stage a woman’s eggs are treated with fertility medications (to improve egg quality) when undergoing infertility treatment; therefore, for optimal treatment, it’s desirable that she a high number of eggs for the medication to work on. One of the most important hormones that facilitate the survival of a woman’s eggs to this mature stage is the hormone androgen – DHEA is a type of androgen.

DHEA  is the lifeboat ensuring that eggs make it through to this last important stage.

In the video below, Dr. Norbert Gleicher, internationally recognized fertility specialist and researcher from CHR New York, explains premature ovarian aging and DHEA use.

Current knowledge about DHEA

Although DHEA is a relatively new infertility treatment, there’s a wealth of clinical research out there to support its use to improve pregnancy chances when used during IVF.  There are also ongoing clinical trials, of which we will see the results in a few years to come. For the moment, from a clinical research point of view, the outlook for DHEA use in premature ovarian aging looks good.

Will DHEA help you get pregnant?

There’s no such thing as a miracle treatment for infertility that can guarantee pregnancy (even though we’d all love one). If you have diminished ovarian reserve, DHEA supplementation, in addition to careful management by your fertility specialist, could be a great option to help improve your pregnancy chances.

Further reading

Current research supporting DHEA use:

  • Gleicher N and Barad DH,Increased oocyte production after treatment with dehydroepiandrosterone. Fertil Steril 2005;84(3):756.
  • Barad DH and Gleicher N,Effects of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 2006;21(11):2845-9.
  • Barad DH, et al, Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian reserve. J Assist Reprod Genet 007;24(12):629-34.
  •  Gleicher N, et al,Miscarriage rates after dehydroepiandrosterone (DHEA) supplementation in women with diminished ovarian reserve: a case control study. Reprod Biol Endocrinol 2009;7(7):108.
  •  Gleicher N, et al,Improvement in diminished ovarian reserve after dehydroepiandrosterone supplementation. Reprod Biomed Online 2010;21(3):440-3.
  •  Gleicher N, et al,Dehydroepiandrosterone (DHEA) reduces embryo aneuploidy: direct evidence from preimplantation genetic screening (PGS). Reprod Biol Endocrinol 2010;10(8):140.
  •  Gleicher N and Barad DH,Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR). Reprod Biol Endocrinol 2011;17(9):6