Zika Virus: What should infertility patients do?

January 31, 2016Carole 1 Comment »

The Zika virus has been in the press recently. It is a virus that is carried by a type of mosquito (Aedes aegypti )  that is found in much of the Americas. The CDC has posted a map of active infections areas here.

Currently, the most active zones are in South and Central America. For most persons infected with the virus, it’s not a big deal. The virus is usually cleared from the blood by the body within a week after infection and the person may have either no symptoms or may have some fever, rash, conjunctivitis that might be associated with a mild flu or cold.

Infection with the Zika virus may be of much greater concern to pregnant women because there may be a connection between being infected with the virus and an increased risk of having a child born with a birth defect called  microcephaly (small head).  This birth defect is particularly scary because it causes life-long issues with brain function including :

  • Seizures
  • Developmental delay, such as problems with speech or other developmental milestones (like sitting, standing, and walking)
  • Intellectual disability (decreased ability to learn and function in daily life)
  • Problems with movement and balance
  • Feeding problems, such as difficulty swallowing
  • Hearing loss
  • Vision problems

Currently, because there is no vaccine to prevent infection or medicine to treat Zika virus infection– the best option is to take steps to prevent exposure to the virus.

Until more is known, CDC recommends special precautions for pregnant women and women trying to become pregnant (copied below from the CDC website) :

Pregnant women in any trimester should consider postponing travel to the areas where Zika virus transmission is ongoing. Pregnant women who do travel to one of these areas should talk to their doctor or other healthcare provider first and strictly follow steps to avoid mosquito bites during the trip.

Women trying to become pregnant or who are thinking about becoming pregnant should consult with their healthcare provider before traveling to these areas and strictly follow steps to prevent mosquito bites during the trip.

Because specific areas where Zika virus transmission is ongoing are difficult to determine and likely to change over time, CDC will update this travel notice as information becomes available. Check CDC’s Zika Travel Information website frequently for the most up-to-date recommendations.

Q: I am pregnant. How will Zika virus affect me or my unborn baby?

A: CDC has issued a travel notice (Level 2-Practice Enhanced Precautions) for people traveling to regions and certain countries where Zika virus transmission is ongoing.

This notice follows reports in Brazil of microcephaly and other poor pregnancy outcomes in babies of mothers who were infected with Zika virus while pregnant. However, additional studies are needed to further characterize this relationship. More studies are planned to learn more about the risks of Zika virus infection during pregnancy.

Q: Is it safe to use an insect repellent if I am pregnant or nursing?

A: Yes. Using an insect repellent is safe and effective. Pregnant women and women who are breastfeeding can and should choose an EPA-registered insect repellents and use it according to the product label.

Q: If a woman who is not pregnant is bitten by a mosquito and infected with Zika virus, will her future pregnancies be at risk?

We do not know the risk to the infant if a woman is infected with Zika virus while she is pregnant. Zika virus usually remains in the blood of an infected person for only a few days to a week. The virus will not cause infections in an infant that is conceived after the virus is cleared from the blood. There is currently no evidence that Zika virus infection poses a risk of birth defects in future pregnancies. A women contemplating pregnancy, who has recently recovered from Zika virus infection, should consult her healthcare provider after recovering.

Q: Should a pregnant woman who traveled to an area with Zika virus be tested for the virus?

A: See your healthcare provider if you are pregnant and develop a fever, rash, joint pain, or red eyes within 2 weeks after traveling to a country where Zika virus cases have been reported. Be sure to tell your health care provider where you traveled.

Q: Can a previous Zika virus infection cause someone who later becomes pregnant to have an infant with microcephaly?

A: We do not know the risk to the baby if a woman is infected with Zika virus while she is pregnant. However, Zika virus infection does not pose a risk of birth defects for future pregnancies.

Q:Is it safe to get pregnant after traveling to a country with Zika virus?

A: If infected, Zika virus usually remains in the blood of an infected person for about a week. The virus will not cause infections in a baby that is conceived after the virus is cleared from the blood. (CW Note: That is true if the virus is not harbored in the semen, but there are a couple of cases which suggest that it may linger in the semen after being cleared from the blood- see the bottom of the post for more information).

Q: Can a pregnant woman be tested for Zika weeks or months after being in a country with Zika?

A: At this time, and for several reasons, we do not recommend routine Zika virus testing in pregnant women who have traveled to a country with known transmission. First, there can be false-positive results due to antibodies that are made against other related viruses. Second, we do not know the risk to the fetus if the mother tests positive for Zika virus antibodies. We also do not know if the risk is different in mothers who do or do not have symptoms due to Zika virus infection.

Q: If a woman who has traveled to an area with Zika virus transmission, should she wait to get pregnant?

A: We do not know the risk to an infant if a woman is infected with Zika virus while she is pregnant. Zika virus usually remains in the blood of an infected person for only a few days to a week. The virus will not cause infections in an infant that is conceived after the virus is cleared from the blood. There is currently no evidence that Zika virus infection poses a risk of birth defects in future pregnancies. A women contemplating pregnancy, who has recently traveled to an area with local Zika transmission, should consult her healthcare provider after returning.

Perhaps most troubling for couples trying to conceive is that there have been several cases in which the Zika virus was found in the semen of men infected with the virus. Most troubling, the virus persisted in the semen long after it was cleared from the blood so a blood test would have shown negative for Zika. This New York Times article, Zika Virus: Two cases suggest it could be spread through sex; raise the specter of a much longer time of caution – perhaps several months- to allow the infected sperm to be cleared from the body, before conception should be attempted.

Bottom Line for couples trying to get pregnant:

  • Avoid traveling to areas that have active areas of infection, if possible. Note that the mosquito that carries the Zika virus is currently very active in South and Central America,  but the same mosquito is found in some more tropical regions of the southern US, but so far the spread of infected mosquitoes has not become a public health issue in the US- due to aggressive mosquito control measures.
  • If you must travel to hotspot areas, use preventive measures (DEET sprays, mosquito netting etc.)  to avoid exposure to mosquito bites.
  • Check the CDC site for updates at  http://www.cdc.gov/zika/index.html ; and consult with your physicians before traveling to these areas, or after your return if you think you may have been infected.
  • If you are a man who has traveled to these hotspots, and you know you have been infected with the virus, or have been bitten by mosquitos, it may be advisable to have only protected sex with your partner for a couple of months after your return. Alternatively, you might consider having your semen cryopreserved in advance of your travel, if you anticipate travel to highly infectious regions and plan to conceive a child soon after your return using IVF/IUI.

Other articles about the Zika virus:

Scientists are Using Genetically Modified Mosquitoes to Fight the Mosquito-Borne Zika Virus

Zika Virus “spreading explosively” in the Americas, WHO says

A new blog: Smart Fertility Choices

November 15, 2015Carole 1 Comment »

If you are looking for a smart, empathetic blog about current IVF information written by someone who is still on their infertility journey – look no further. A months old website, Smart Fertility Choices , written by Kym Campbell,  is an inspiring mix of blog posts and pod casts. What makes her blog different from most is she is diligent about digging into the scientific basis for all questions IVF and is not afraid to speak to experts directly on her podcasts. She reads and references published journal articles to back up her summaries on various topics. I also like that her blog does not currently post advertisements and all the info is free. In her podcasts, she interviews experts in the field for their perspective on best practices.

Kym starts her second pod cast with her own infertility journey. In future podcasts, Kym  plans to interview women who are still on their infertility journey. I think it is so very important to have a place to share these stories so that women know that they are not alone in these experiences. Kym realizes that it is important to share not only the “had a baby” success stories but also show how couples have found a meaningful life after infertility treatments even if the original path to parenthood took a zig-zag or if that future life is child-free.

The other thing I like about Kym’s approach is that she is not passive about her healthcare –she asks questions of her doctors, and other experts to better understand what options she has and the pros and cons of different options. Her story of seeing 6 specialists is very instructive because it illustrates that not all specialists are equal in quality–and that if your gut tells you something about the treatment plan does not make sense or your doctor’s style of communication is not a good fit- it is perfectly fine to move on and talk to someone else.

On her website, Kym provides resources for working toward your best physical and mental health prior to and during your infertility treatments. Starting with good overall health is important not only because it might shorten your infertility journey, but supporting your emotional health as you undergo the rigors of treatment makes it easier to tolerate the inevitable emotional roller coaster that are a side effect of treatment. Being in your best physical condition also prepares you for the actual physical demands of pregnancy. Kym shares information about mindfulness exercises, acupuncture and other adjunct therapies which were very useful for her and may be useful for other patients. These resources are intended to  help patients take the long view because everyone needs to find happiness in life, however the infertility journey ends.

Kym knows a little something of taking life by its tail and living it to the fullest. She grew up in Seattle, Washington, moved to  California for college to study Economics, then traveled to Australia for a study-abroad program in 2001. Returning to Australia for a Masters in Accounting in 2004, she fell in love with the sun, surfing and musical inspiration she found in Australia. She picked up a guitar and began writing songs, her music career culminating with international success, including touring in Japan. You can hear her beautiful island inspired music on You tube, and every podcast “cheekily” ends with one of her songs.  As an admitted “Type A” personality, when she and her husband ran into obstacles with starting her family, she plunged into this new fertility challenge with the same amazing (to me) energy and enthusiasm she’d shown for economics, surfing and music.  I think you will enjoy meeting her and joining her on her journey as she works through various options, without losing her sense of humor and her love of life. You may find her attitude inspirational. I do.



Financial Assistance Grants for Infertility Patients

October 17, 2015Carole 2 Comments »

As the technology for infertility treatments improve more and more- the bigger issue for many couples is not finding a good treatment option for them but finding a means to pay the costs of those treatments. Did you know that there are foundations and organizations that offer grants to patients with financial need to help with costs associated with infertility?

You can find an up-to-date list of grants  to support infertility treatments, adoption, fertility preservation, fertility medication discounts and military discounts on the Fertility Within Reach website. The following foundations offer grants to pay for infertility treatments: AGC Scholarship Foundation, The Angels of Hope Foundation, BabyQuest Foundation, The Kyle and Samantha Busch Bundle of Joy Fund, The Cade Foundation,
The Fertility Foundation of Texas, 
INCIID IVF Scholarships, Journey to Parenthood, Kevin J. Lederer Life Foundation, The Life Foundation, New York State Infertility Demonstration Program, Pay-It-Forward Foundation,  Sparkles of Life.

Other foundations offer grants to pay for the costs of adoption:  National Adoption Foundation Financial Programs, Gift of Adoption Fund,  Help Us Adopt.ORG, Show Hope.

You can also find grants to pay for fertility preservation prior to undergoing cancer treatment or for infertility treatments for cancer survivors: Sharing Hope Financial Assistance Program, and Fertile Action.

The non-profit organization Fertility within Reach also offers grants through its Banking on the Future grant program to pay for preservation and storage of gametes for young patients  (under 21) faced with cancer treatments.

There are also programs that offer grants or discounts to cover the costs of fertility medications including IVF Greenlight offered by Ferring Pharmaceuticals Inc. , Compassionate Care by EMD Serono, or the First Steps Program offered by DesignRx pharmacies.

You should also know that your fertility clinic is likely to be open to offering you a discount for cash or military service discounts if you or your partner are in the military. It never hurts to ask your clinic or your pharmacy directly about unadvertised discounts they may have.

For military veterans and their spouses, The Compassionate Corps Program provides free fertility medication to those who are eligible. 

Feeling overwhelmed by the options? Each program has varied eligibility requirements and it may seem daunting to search through them all. Fortunately, Fertility Within Reach has summarized the eligibility requirements for each of these programs on their site. To find the eligibility requirements for each of these,  visit Fertility Within Reach’s website financial assistance grants page to find the  grants that you can apply for. Also, check out Fertility Within Reach’s   Financial Assistance Application Guide.  This page provides tips on how to properly fill out a grant application to ensure you have an opportunity for consideration.

You are Stronger, Braver, Smarter than you think…..

September 13, 2015Carole 2 Comments »

Post from 2012- but still an important message for patients struggling with the emotional toll of infertility….

Sometimes wisdom can be found in the oddest places. I came across this quote from Winne the Pooh.

“Promise me you will always remember: You are stronger than you seem, braver than you feel, and smarter than you think,” — Christopher Robin to Pooh.

This is the message I hope to pass on to all of you struggling with infertility. Infertility can take control of your life, darkening your spirits and making you question your  entire life, your choices and decisions, past and future. It can make you question everything, even your place in the world. Don’t let it. You will get through this. The ending may not be written the way you expect but you will find an answer for yourself. You will do the best you can with what you have. You are stronger than you seem.

Don’t give up hope that a better day lies ahead. No one can promise you a biological child. Even the best science can’t guarantee that. But you will get through this. There is a morning after infertility where you either face the brand new challenges of parenthood (one way or another)  or find another path to nurture the future, your way. You are braver than you feel.

Don’t let someone else push you to do something that  you don’t understand or that troubles you for some reason. Ask questions until you feel confident about your choices and can make the best decision for yourself and your family. If your  doctor can’t or won’t explain something, find another who will.  If something sounds too good to be true, it probably is. You are smarter than you think.

Promise me you will always remember: You are stronger than you seem, braver than you feel, and smarter than you think.

Q from U: if I transfer this embryo, will I get pregnant?

June 6, 2015Carole 23 Comments »

One question that comes up again and again from IVF patients is: If I transfer this embryo, will I get pregnant?  Patients send me their pictures of embryos and ask me to evaluate them and predict whether this embryo is “the one” that will become their longed for child.

I deeply understand this need to see into the future and gain the knowledge to make the right decision in the present, but it is impossible to predict with certainty an outcome from IVF- especially from a photo. It might help to understand why this is still impossible to do.

Embryologists are tasked to recommend embryos for transfer based on information they can collect while they have the embryos growing in the lab. The 3 main indicators used by embryologists to determine the best embryos are:

1. Does the embryo look “good”? This was the first tool embryologists used but it has been eclipsed by two other tools I’ll talk about in a little bit. Even with only a weak correlation between appearance and implantation/pregnancy success, embryologists were desperate to identify some measures to predict which embryos were most likely to implant and go to term. Some traits –such as an even number of same sized cells at each cleavage stage –seemed advantageous for implantation. Likewise, very little fragmentation of cells also seemed like a good trait for an embryo to have. So regular, even embryos with no or few fragmented cells received higher scores than embryos that had irregular shaped cells and/or lots of fragments. It might have spoken more to our bias regarding beauty- we like symmetrical things and even numbers- and was not based on compelling science that these traits always correlated with pregnancy success. This lesson was brought home to me with two IVF cases very early in my career. One patient was 40 years old with perfect-scoring textbook-looking 8 cells on day 3. The other patient was in her twenties, had a large number of embryos, with each one scoring worse than the next due to large amounts of fragmentation. In fact, it was hard to tell for some embryos if a cell was actually a cell or a large fragment. Based on scoring, we had higher expectations for the 40 year old, but it was the younger patient who got pregnant and this lovely baby was the first IVF baby I was privileged to hold when the patient brought her into the office when she was a couple of months old. This taught me that embryo scores alone could be misleading.

2.  Did the embryo hit certain developmental stages on time or did it stall or lag? This is a functional question which is more directly tied to whether an embryo is likely to keep growing, than an embryo score. Our first real chance to evaluate embryo function was with the advent of sequential culture systems which allowed embryologists to grow embryos for 5-6 days, allowing them to determine if the embryo was able to reach blastocyst stage- the stage just before implantation. We now know that for some patients, a significant number of embryos get stalled at cleavage stages. When embryos were routinely cultured to day 3 to transfer embryos at cleavage stage – and the cycle failed- there was no way to know if this particular embryo would have also stalled out in culture. Now, this embryo has a chance to fail in culture and not be selected for transfer. With the advent of time-lapse continual video monitoring of embryos, and mathematical analysis of these videos- embryologists are able to determine the average times to reaching developmental stages for embryos that go on to implant.  This analysis of an embryo’s functional capacity to grow– has been taken to another level.

3. Does the embryo have a normal number of chromosomes? Chromosomes are twisted strands of DNA that contain all the genetic information passed on from the parents. With only a few exceptions, having an abnormal number of chromosomes is incompatible with continued embryo growth, implantation, pregnancy and live birth. For instance,  Trisomy 21 (an extra Chromosome 21) is compatible with life and these kids are born with Downs Syndrome. With pre-implantation genetic screening (PGS) of embryos, we can tell if an embryo has a normal number of chromosomes. This is a big deal. While aneuploidy testing does not rule out the possibility that an embryo could be harboring smaller stretches of DNA sequences that could doom it along the way- it does rule out really big problems like the absence or addition of entire chromosomes. It is also possible to use pre-implantation genetic diagnosis (PGD)  testing to look for abnormal gene sequences that are harbingers of severe medical conditions later on- but these usually don’t impact implantation potential- in the way that most kinds of aneuploidy do.

The good news is that embryologists have more and better tools at their disposal to evaluate embryos for their potential to implant- and these are certainly evolving and existing tools will improve and new tools will be added as time goes on- but even if your embryologist can find your “best chance” embryo, it still does not guarantee your pregnancy.

IVF is a team effort, not just in the clinic, but also between the patient and the clinic. The physician has to be aware and counsel the patient of other issues that may also be reducing the patient’s chances of conception and a healthy pregnancy.

  • Endocrine problems (eg. thyroid conditions)  that effect reproductive function. If a patient is hypothryoid or hyperthyroid, these conditions must be brought under control first.
  • Insufficient (thin) uterine linings that are inhospitable to embryo implantation. In some cases, a frozen embryo transfer may be more optimal because it separates the IVF case into a ’embryo production” phase in which egg quality and selection can be optimized hormonally and an “embryo implantation” phase in which the uterine lining can be optimally hormonally primed for implantation. The best hormonal protocol for each are often not the same and the lining gets short changed to get more eggs at retrieval.
  • General health of the patient. Patients that are at the extremes of weight (over or under) may have more difficulty conceiving. Patients who smoke also reduce their fertility- this applies to both males and females. There are lots of factors that go into good reproductive health- these are just a few. It is important to share all your medical information with your doctor so they can try to help you optimize your reproductive health before you spend a lot of emotional and financial resources on IVF.

Bottom line, getting pregnant should be easy, but it often isn’t. Even high tech procedures can’t guarantee pregnancy. You can, however,  position yourself for the best possible outcome by finding a highly effective IVF team (look at www.sart.org for  best pregnancy rates in your area)  that will work with you to diagnose the problem (look for good two-way communication between the patient and clinic), grow and find the best embryos to transfer (look for a good lab that uses modern tools) and helps you optimize your fertility before you even get started (good physician practice).

I have a lot of faith in patients to make the right decisions if they have all the information they need along the way. I choose patient education over a crystal ball any day to get a happy answer to the question: Will I get pregnant if I transfer this embryo?


Making your case for IVF coverage

April 20, 2015Carole No Comments »

The dance between doctors and insurance companies  to get medical procedures covered is a common part of medical treatment. Doctors will often write letters to the insurance company to confirm that the patient 1) needs the procedure and 2) the procedure is likely to work or provide benefit to the patient.

You can enlist your doctor’s help and provide him with ammunition to use in his letter on your behalf by visiting the Fertility Within Reach website  at http://www.fertilitywithinreach.org/infertility-resources/ and checking out all their free resources.

Tip of the Day. If you provide your first name and your email to sign up for their newsletter, you will get a free copy of Policymaker’s Guide to Infertility Health Benefits. This booklet contains lots of easily digestible facts to share with your insurance company and/or your employer that demonstrate that fertility benefits for everyone- and specifically you!!- are a win-win for all concerned.

Fertility Within Reach also offers patient coaching for a fee if you want it but there is a lot of free information that is very accessible on the web site and there is no pressure to buy the coaching sessions. But if you want to have a patient navigator, there is no one better than Fertility Within Reach founder Davina to coach you. She has been an infertility patient herself and knows what having infertility coverage means for a patient. The website and Policymaker’s guide are a compilation of all the wisdom she has accumulated over the years helping patients get access to IVF coverage.

Other resources for advocating for insurance benefits:

Via Fertility Within Reach:

Infertility Insurance Resource Information by State: http://www.fertilitywithinreach.org/infertility-insurance-information/lobbying-101/state-resource-information/

Free Policy Makers Guide: http://www.fertilitywithinreach.org/policymakers-guide/

Communicating with your Insurance Provider: http://www.fertilitywithinreach.org/communicating-with-your-insurance-provider/

Communicating with your Employer: http://www.fertilitywithinreach.org/communicating-with-your-employer-about-fertility-benefits/

Via Patient Advocacy Foundation (General medical- not infertility specific)

How to Write an Appeal Letter if you are denied: http://www.patientadvocate.org/resources.php?p=36

Remember that just because you don’t have coverage or your coverage is incomplete today- that doesn’t mean that it needs to stay that way. There are effective methods to get the coverage you need and organizations to guide you on your way.

UPDATE: If you are in Massachusetts, Fertility Within Reach is having a special seminar on empowering patients to get health insurance coverage. The event is happening on May 16, 2015 This workshop is called, Funding Fertility Treatment: Empowering Yourself to Access Insurance Benefits & Financial Resources and is being held in Natick, MA.  For more information and to register, go  to Davina’s blog post.

FWR Funding Fertility Tx Workshop


Can supplements really improve sperm quality?

January 25, 2015Carole No Comments »

One of the questions I often get is from patients who want to know if there is a supplement they can take to restore their fertility. Some of the supplements are little more than a tweaked daily vitamin with a “fertility optimized” mix of vitamins. They probably won’t hurt you but hard scientific evidence is weak at best to enthusiastically recommend that everyone get on the supplement bus.

All of us would like if science could issue a unequivocable result for every question we are struggling with. How can we find the best health care practices when there are so many studies with conflicting results? Which studies should we believe? How can we better understand what the science is telling us? One method is through the Cochrane Collaboration which is an organization and a methodology to look at multiple studies that are asking the same question and identifying studies that were well done (appropriate controls used, good statistics, reproducibility of results) and looking for a common, evidence-based message.  The purpose of doing an Cochran review is to find the truths in studies so that patients can benefit from evidence based health care instead of anecdotal stories and a physician’s own limited experience.  The methodology that is used for a Cochrane review is explained here.  Briefly, a Cochran systemic review “is a high-level overview of primary research on a particular research question that tries to identify, select, synthesize and appraise all high quality research evidence relevant to that question in order to answer it.

Key Points:

  1. Systematic reviews seek to collate all evidence that fits pre-specified eligibility criteria in order to address a specific research question
  2. Systematic reviews aim to minimise bias by using explicit, systematic methods
  3. The Cochrane Collaboration prepares, maintains and promotes systematic reviews to inform healthcare decisions: Cochrane Reviews

A patient wanted to know which supplements are best to treat DNA fragmentation in the sperm head, which degrades fertility.

In a published Cochran review in 2013, Dr. Marian G. Showell and colleagues published “Antioxidants for Male Subfertility”. The abstract of their study can be found here and the full article with a “plain language summary” here, and copied below:

Review question: do supplementary oral antioxidants improve fertility outcomes for subfertile men when compared with placebo, no treatment or another antioxidant?

Background: many subfertile men who are part of a couple undergoing fertility treatment are also taking dietary supplements in the hope of improving their fertility. It is important that these men have access to high quality evidence that informs them on the benefits and risks of taking an antioxidant. This review aimed to assess whether oral antioxidants would increase the chances of a couple with a subfertile male partner achieving a clinical pregnancy and ultimately a live birth. This review did not examine the use of antioxidants in men with normal sperm.

Study characteristics: the Cochrane review authors included in this updated review 48 randomised controlled trials that compared single and combined antioxidants with placebo, no treatment or another antioxidant in a population of 4179 subfertile men. The duration of the trials ranged from 3 to 26 weeks with follow up ranging from 3 weeks to 2 years. The men were aged from 20 to 52 years. Most of the men enrolled in these trials had low total sperm motility and sperm concentration. One study enrolled men after varicocelectomy (surgical removal of an engorged vein in the scrotum), one enrolled men with a varicocoele (an engorged vein in the scrotum) and one recruited men with chronic prostatitis (infection of the prostate gland). Three trials enrolled men who, as a couple, were undergoing in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) and one trial enrolled men who were part of a couple undergoing intrauterine insemination (IUI). The data were current to 31 January 2014.

Funding sources were stated by 15 trials. Four of these trials stated that funding was from a commercial source and the remaining 11 obtained funding through non-commercial sources or university grants. Thirty-three trials did not report any funding sources.

Key results: antioxidants may have been effective in treating subfertile men but the reporting of studies was too inconsistent to be confident in these findings. The live birth results suggest that we would expect a live birth of a baby for 5 out of 100 subfertile men who did not take any antioxidants, compared to between 10 and 31 out of 100 men who were taking antioxidants. The results for the clinical pregnancy rate showed an expected clinical pregnancy for 6 out of 100 subfertile men who did not take any antioxidants, compared to between 11 and 28 out of 100 men who were taking antioxidants. Adverse events were poorly reported and we could not make conclusions on any harmful effects. More high quality, larger placebo-controlled trials reporting on these outcomes and adverse events are needed to draw definite conclusions.

Quality of the evidence: the quality of the evidence for live birth and clinical pregnancy was deemed ‘low’ while adverse events was assessed as ‘very low’. These ‘low’ and ‘very low’ assessments were due to the lack of a clear description of trial methods and inconsistent, inadequate reporting of live births and clinical pregnancies. Not enough trials compared the same interventions to make any conclusions about whether one intervention worked better than the other.

Bottom line: We need better studies to determine whether oxidants are beneficial.  In the absence of these studies, it is prudent to have a discussion with your doctor about the risks/benefits of any supplement you may be considering.

Fireworks at Fertilization

December 26, 2014Carole 3 Comments »

A new study shows that the genesis of a new human being is accompanied by fireworks. The amazing fireworks display that the egg puts on using zinc atoms when the egg is fertilized is shown in the video below.

In an article published in Nature Chemistry, Dr. Theresa Woodruff and her team discovered that the newly fertilized egg releases tiny packages of one million zinc atoms each that creates waves of light, called zinc sparks. These waves of lights happen four to five times in the first hours after fertilization and are necessary steps for the egg to begin its development to an embryo.

This discovery could be the beginnings of an analytical method to distinguish the healthiest fertilized eggs among a group of in vitro fertilized eggs. Being able to better select the healthiest fertilized eggs would increase the likelihood that only one embryo can be selected for  transfer and that the selected single embryo will be able to go the distance, implant and produce a healthy pregnancy and child.

Here is another article about this discovery with quotes from the team.

INVOcell- Analysis of Risk vs Benefit

November 11, 2014Carole 2 Comments »

Just the other day, I stumbled across an article published on Oct 24, 2014 that discussed a oral presentation presented at the recent ASRM meeting about a low cost IVF alternative called INVOcell. To my surprise, I found comments I made more than two years ago appearing in the current article although no one actually contacted me before they wrote the latest piece. So I thought I would revisit the issue, look at the new data and see whether I can learn to love INVOcell.

What is INVOcell?

INVOcell is IVF without the in-lab culture part. Like IVF, the INVOcell procedure has an ovarian stimulation cycle part to recruit eggs (check). An egg retrieval is performed  to get eggs (check). Eggs and sperm are put together (check), – in a plastic container which is placed in the vagina so the patient can vaginally incubate her gametes. (Whaat?= that’s the INVOCell part).  After 3-5 days, embryos are removed from the container and transferred back to the patient’s uterus.

So, back in 2011 I had two main concerns with this low cost alternative to IVF which I expressed in this post:

Invocell- not nearly IVF

Concern One. If eggs in cumulus and sperm are added to a small culture volume, these other cells will degrade the quality of the culture  medium as they incubate. That is why we remove these excess cells at fertilization check the next morning and place in fresh media. The newest version of the INVOCell technique uses either a very short co-incubation period for sperm and eggs with removal of excess cells before the egg goes into the container or ICSI to minimize the cellular material from the beginning to one egg with a sperm inside. Both of these are good solutions to the media degradation issue and so I am not worried about this any longer.

Concern Two: The fertilization check step is skipped. The window during which normal fertilization can be seen in the form of two pronuclear structures (2PN) inside the egg visible using a microscope happens during the time the egg is incubated in the INVOcell device inside the vagina- so obviously it doesn’t happen. The physician has the option to remove the vaginal device and open it, remove the embryos and check for fertilization but this is not routinely done. After all, the low cost part of INVOcell is due in part to the fact that you don’t do a lot of monitoring and checking during culture (reduced staff) , and don’t need to buy a lot of incubators (reduced equipment overhead since the patient brings her own vagina or that of a good friends to the case). I think INVOcell can be offered at half the price of regular IVF. The stim cycle drugs and physician/nurse time are still expensive but the lab expense can be minimal.

So what’s the big deal with skipping the fertilization check step? 

The reason we don’t skip this step in the IVF lab is because even abnormally fertilized eggs pretty routinely grow into very nice looking blastocysts which can’t make a normal baby but can make trouble if transferred- namely resulting in a molar pregnancy which is one of the complications under the category of gestational trophoblastic disease (GTD) .  Very rarely, a cancer (choriocarcinoma) can arise from GTD.

What causes the most common form of GTD ( hydatiform moles- aka.  molar pregnancies)  which can (rarely) result in choriocarcinomas?

Two types of fertilization errors cause GTD. First, an extra sperm enters the egg, resulting in a 3PN state, DNA from three gametes  (egg, sperm, sperm) instead of two (egg, sperm). Alternatively, the egg can fail to toss out its extra set of chromosomes before a single sperm gets inside- again you have DNA from three gamete sources (2 from the egg plus one sperm) causing a 3PN state instead of the normal 2PN state.

Can we tell if we have a normally fertilized egg or not and remove it from the pool of embryos eligible for transfer?

Yes, traditional IVF procedures require a “fertilization check” step to visually examine the fertilized egg under the microscope during a specific time period (16-20 hrs after sperm are added to the egg) to verify whether 2 pronuclei are visible (normal 2PN state) or more than two are visible (abnormal 3PN) state.

The INVOCell procedure does not include a check for 2PN status.

How often does gestational trophoblastic disease happen? From the American Cancer Society link:

Gestational trophoblastic disease (GTD) occurs in about 1 pregnancy out of 1,000 in the United States. Most of these are hydatidiform moles.

How often does GTD convert into a cancer? From the National Cancer Institute link:

The reported incidence of choriocarcinoma, the most aggressive form of GTD, in the United States is about 2 to 7 per 100,000 pregnancies. The U.S. age-standardized (1960 World Population Standard) incidence rate of choriocarcinoma is about 0.18 per 100,000 women between the ages of 15 years and 49 years.[2]

So the incidence of this across all pregnancies (natural and presumably some from IVF in this sample)  is relatively rare.

So why worry about GTD at all?

One reason I am not 100% relieved at this low incidence rate is that we don’t actually know what the rate of molar pregnancy is in IVF patients. I do know that in my experience, we could expect to have a least one molar pregnancy a year in our program.

What was the clinical outcome for IVF patients with a molar pregnancy? These patients had a D&C and then they were counseled not to attempt pregnancy for another 12 months just in case some of the cellular material was retained and could result in an undiagnosed choriocarcinoma. Molar pregnancy was a relatively infrequent event, but something that was treated very seriously when it happened.

There are various anecdotal reports of molar pregnancies in the published literature but I couldn’t find any  national statistics in the incidence of molar pregnancies arising from IVF. Yet, almost every program will, if asked, tell you that yes, they  have had IVF patients with molar pregnancies – and this is under regular IVF protocols in which  3PN embryos are routinely detected and removed from the groups of normal embryos for transfer.

So what can we expect if we skip this step? Will increased use of INVOcell unwittingly lead to the transfer of more abnormal 3PNs – some of which may implant and cause GTD?

Although we may not know the incidence of molar pregnancies in US IVF programs, I know that 3PNs are commonly present among the normally fertilized eggs of many of our patients. How do I know this? I know this because my lab would freeze these non-clinical embryos on a weekly basis (with patient permission) to use these as embryos for technical training. Techs could practice moving embryos from dish to dish or practice freezing or thawing them. We had 3PNs every week to freeze. We pulled them out of the clinical transfer pool but they were routinely arising in our culture system. They made great practice cells because they looked so normal.

So if we don’t look for them in the INVOcell system, does that mean they don’t happen?

My first post back in 2011- caused a big reaction on the part of a reader “Boris”. I took the bait and responded to him in a second, snarky post.INVOcell post strikes a nerve. It’s hard to tell who was suffering from more nerve pain- me or Boris.

In any case, more than two years after my last INVOcell post, earlier this month at the ASRM meeting in Honolulu, data from a small US study was presented that showed encouraging results with INVOcell compared side by side with regular IVF. You can decide if the new data warrants the exuberant headline from the  ASRM press release “Intravaginal incubation of embryos is safe and could save patients money.”

This new INVOcell study was presented by Dr. Kevin Doody from Bedford, Texas as an oral presentation at the meeting. The ASRM abstract data is presented below and  the entire abstract can be found at this link.  There’s not a lot there about how the INVOcell procedure was done except for this: “After a 2-4 hour co-incubation with sperm, up to 10 eggs were placed into the INVOcell device or into traditional incubators. After 5 days, one or two embryos were transferred into the uterus.” Since the window for fertilization check is after 16-20 hours, it’s probably correct to say that fertilization check step is still not part of the INVOcell procedure.

Incubator INVOcell
Number of cycles (patients) 16 17
Mean age 32.3 (26-38) 32.8 (26-38)
Mean body weight (pounds) 162.0 (121-207) 151.5 (109-184)
Mean number of oocytes inseminated 7.6 (1-10) 6.7 (3-10)
Mean number of embryos transferred 1.8 1.65
Mean blastocyst quality score (BQS) 27.24 26.14
Ongoing pregnancy rate /cycle 62.5% 58.8%

The patients in the study are fairly young (on average less than 35) and there were 16 patients in the Incubator method and 17 in the INVOcell method. Statistically speaking, 17 test patients is probably insufficient to detect the risk of GTD.

According to the Medscape article, another clinician, Dr. Lucena, in Bogota, Columbia says that she has seen no adverse outcomes in approximately 500 cycles, which while encouraging is probably still not enough cycles to detect an increased risk of GTD. It is also possible that other factors like advanced maternal age, may make a patient more prone to producing 3PN embryos. We just don’t know enough yet.

These early results are promising in that these patients had very comparable pregnancy rates between regular IVF and INVOcell. The FDA has not approved INVOcell yet for routine use in the US, but one INVOcell clinical trial(2011) is listed on the US government list of clinical trials.

I would be happier if we had more data and I would be ecstatic if we had some test to tell that these embryos are normal when they are removed from INVOcell culture and before they are used clinically. In theory,  genetic testing could be performed on INVOcell embryos but that would make INVOCell more expensive.

Is INVOcell safe? I don’t know. Most of the time when you drive around in a car without seat belts, no harm done. But sometimes, if you are unlucky, you can have preventable injuries if the car does crash. I would rather see more patients have access to insurance policies that pay for traditional IVF that has all the safety features, rather than encourage patients to use a cheaper procedure which may be riskier. Most patients will have no trouble but a few may have very bad trouble. In the end, it boils down to an analysis of risk vs. benefit. If you are enrolled in a clinical trial with INVOcell, hopefully the risk of GTD –as much as can be known- will be disclosed to you before you take part in a trial and you can decide:  Do you feel lucky?


Disclosure: As an ex- embryologist,  I have no financial interest in the performance of  EITHER regular IVF or INVOcell. As a patient advocate, I am always hoping for better infertility treatments and better access to these treatments for patients.

Egg freezing is no guarantee for future fertility

October 19, 2014Carole 5 Comments »

In 2013, the American Society for Reproductive Medicine (ASRM) declared that egg freezing was no longer experimental. Here is a link to the professional guidelines, which say in part: “There is good evidence that fertilization and pregnancy rates are similar to IVF/ICSI with fresh oocytes when vitrified/warmed oocytes are used as part of IVF/ICSI for young women. Although data are limited, no increase in chromosomal abnormalities, birth defects, and developmental deficits has been reported in the offspring born from cryopreserved oocytes when compared to pregnancies from conventional IVF/ICSI and the general population. Evidence indicates that oocyte vitrification and warming should no longer be considered experimental.”

I have highlighted some important caveats to this declaration.

  • The method of freezing makes a difference. Old-style slow freezing is not included because most US labs never demonstrated that slow egg freezing could repeatedly be performed with good results- although some Italian labs were successful with slow egg freezing. Vitrification is not considered experimental- when done expertly.
  • To get the best fertilization results, thawed eggs must be fertilized using ICSI (aka. egg injection) because the egg membranes harden and sperm in culture have a very difficult time pushing their way in to fertilize the egg; the sperm must be injected using a microscopic needle.
  • Outcome data are limited regarding whether the resulting offspring are normal but early results are encouraging.

If you read the entire document- which I strongly encourage you to do if you are thinking about egg freezing- you will notice that the authors raise the issue of generalizability of these results to all labs everywhere. The pregnancy data that was referenced was all from the frontier labs who took this method up as a major initiative in their lab and really worked hard to get those positive results. Even with vitrification, egg freezing is not an easy technique. It does not take long to do but in that short time between immersing an egg into toxic cryopreservation fluids, and plunging the container with the egg into liquid nitrogen, there are about twenty different ways to make a mistake and little or no time to fix it so you better be both fast and good at the hand work. That takes both excellent training and practice. This is made more complicated because there are about 10 different containers to freeze eggs in and various kinds of vitrification medium being produced by different companies all vying to tell labs that their method/media/container is the best. So it is not like there is one obvious best method that all labs can just get busy and learn to do well. There is no obvious best standard of care.

In one of my labs, we had great difficulty in reproducibly getting good results with vitrification even though our pregnancy rates with IVF and FET cycles were the best in the state. This is evidence that just because you have mastered one skill set, doesn’t mean that a new technique won’t require significant time and effort to master.  So when the “experimental” label was removed from egg freezing, my first reaction was dismay because I knew that a lot of clinics would recognize an opportunity to offer a new service –and make a lot of money–without necessarily making the investment in staff and training to do it expertly. A lot of first patients at these rush-to-offer egg freezing clinics would be guinea pigs who would happily pay their money and not know whether they had gotten any value for years.

So how are clinics doing? Nobody really knows- it’s not currently part of the data set that must be reported to the CDC- but that will change in the future.  Sure, good clinics are tracking their data internally now but until you thaw (warm) an egg and try to fertilize it and grow it to a blastocyst stage embryo for transfer, you have no idea whether the vitrification and warming worked and your egg is still alive and functional.  Women who are freezing for the future aren’t going to even try to use those eggs for years, so actually getting pregnancy data from vitrified eggs will be slow in coming– making it hard  today for patients to distinguish good egg freezing programs from bad egg freezing programs.

Now Apple and Facebook are covering egg freezing as a benefit for the employees. On the one hand, it is a great thing to remove barriers from reproduction for people who want to have kids. But the potential harm here is that women will think egg freezing is a slam dunk- and that by freezing eggs now, they have a guarantee that they will have functional eggs for producing a pregnancy in the future. I wouldn’t make that bet right now unless your program can prove to you that it has pregnancy outcome data from many, many patients who successfully used their vitrified eggs and are now happily raising these kids.

I know of at least one program that crowed about their success with achieving a single pregnancy from a vitrified egg but then failed to reproduce that event for another patient for months! Actually, I don’t know if they ever did have a second birth. They didn’t believe in writing down their methods so they couldn’t reproduce their success.  That didn’t stop them from aggressively marketing that first pregnancy using every social and media outlet they could find. I am sorry for all the women who went to that clinic based on one case. Yes, eggs were put in storage for the patients the marketing brought in, but there is no guarantee that they can rely on those eggs when they need them. And by the time those thaws happen in any real numbers and patients are unhappy, the greedy bastards who froze their eggs will have retired.

My advice to young women is that they should really push for pregnancy data from any clinic that wants to sell them egg freezing. Unless the clinic can document in writing that their birth rate for women of your age using frozen eggs are are no different than same-aged women using fresh eggs – AND- they have hundreds of successful pregnancies, not just one – don’t use their clinic. And don’t be fooled by their pregnancy data with embryo freezing. Embryo freezing is about 100 times easier than egg freezing so the success rates for one doesn’t necessarily translate into success rates for the other.

If your employer is paying for egg freezing, it’s a good idea to make sure your employer is also paying for annual storage fees and the IVF cycle(s) you’ll need in the future to actually use your frozen eggs.