1. experiencing a dawning of awareness,
2. facing a new reality,
3. having hope and determination,
4. intensifying treatment,
5. spiralling down,
6. letting go,
7. quitting and moving out,
8. shifting the focus

From my interactions with patients in the lab, or via my blog, these stages make a lot of sense. They seem similar to stages of grief or stages of finding sobriety after addiction. Some patients get stuck at step 5, “spiralling down”. They are the patients who are confronted with repeated failures and evidence of new hurdles to their fertility, patients for whom even herculean efforts in terms of effort and expense can be expected to be successful less than 5% of the time. If someone told you that you should bet $12,000, $15, 000, even $20,000 on a horse that has a 5% or less chance of winning the race, you’d tell them to get lost, that’s crazy. Or something much more colorful. Yet, IVF patients that go in for multiple rounds of IVF, beyond two or three are doing exactly that. Most clinics have pulled out all the stops, applied all the tricks they know by the third IVF cycle. If it still isn’t working, either the clinic is incompetent or IVF is not the right solution for that patient.

Here’s a hypothetical case.

Patient is 46 years old, has had 6 IVF cycles since she turned 40. Her husband’s sperm is very poor and even ICSI yields no or very low fertilization. Pregnancies have been elusive or short lived. They need a miracle. What can you tell this patient? They don’t have bottomless financial resources. They don’t want to try or can’t afford donor egg. Accepting a donated embryo, while much less expensive, is not palatable to every couple and is not offered in every clinic. What can you tell them? What is left for them to do?

I found this list of questions which I thought were useful on a WebMD article, Addicted to hope for a child,  and have copied them below:

Knowing when to stop fertility treatments isn’t always clearcut. The following signs, compiled from other couples’ experiences, may help you recognize the point at which ”enough is enough:”

1. The fertility drugs are causing painful or adverse symptoms, ranging from physical pain to severe mood swings.
2. You’re already in debt and cannot afford another cycle.
3. You cannot stand to be around anyone but your partner and your doctor. You can’t remember the last time you chatted with a friend.
4. You can’t remember the last time you did anything for pleasure — reading, sports, going to a movie — that did not revolve around infertility.
5. You and/or your partner are incapable of becoming sexually aroused just for “fun.
6. You eat, drink, and sleep infertility. You’re so obsessed about your infertility that it’s interfering with your job, your sex life, your social network, and your relationship with your partner.
7. You’re showing signs of depression: apathy, loss of interest in formerly pleasurable activities, change in appetite (usually decreased), fatigue, guilt, self-loathing, suicidal thoughts, poor concentration and memory, sleeplessness (waking early and not going back to sleep), and anxiety.

Having worked on the provider side of infertility, I have experienced first-hand the internal conflict I felt between the role of “hope peddler” and “reality checker”. As a professional who is not a physician, I have little leeway in what I say to patients. I am not allowed to give medical advice. I stick to the facts and let patients come to their own conclusions. Sometimes, it was frustrating, especially when I saw some physicians who seemingly never saw an end to offering potential treatments for patients, even those with little or no chance of success. ASRM even published an ethics committee report on the topic: “Fertility treatment when the prognosis is very poor or futile” . You can read the entire paper on-line but here are the take home messages, many of which you can file under “common sense”

1. Definitions: A “futile” treatment is one with less than or equal to a 1% chance of a live birth. “Very poor prognosis” means more than 1% but less than 5% chance of a live birth per cycle.

2.Clinicians can refuse to offer futile treatments, but should consider a referral to another provider, if appropriate. (Appropriate is not defined but maybe Dr. Smith is more optimistic down the street. )

3. Decisions to treat should be patient centered. Protecting your high success rates is not a good reason to deny  treatment. Making money is not a good reason to offer treatment.

4. Clinics can offer futile treatments if the patient has been fully informed about the Risks, Benefits and Alternatives to treatment. My good friend Bob and I disagree about this point all the time. He argues that patients have the right to make all the bad decisions they want, as long as they are fully informed. I agree that they have the “right” but sometimes the consent process is flawed or patients are overawed by their doctor and afraid to ask questions so full informed consent is not always obtained and their best interests are not always served.

5. Thorough discussions are advisable. Decisions to treat or not to treat should be made in cooperation with the couple. The clinic should have evidence -based policies to uniformly offer treatments (or not offer treatments) to patients.

So the bottom line is that, in the end, your doctor can advise you,  but the responsibility to decide is yours.  I have observed doctors prescribe “psychological” IVF cycles, knowing full well that the odds of success were futile, but weren’t imaginative enough or brave enough to find a way to say “no” to the patient when they asked for further treatment. Their solution was to offer up another chance for the patient to experience failure and finally move on with their lives to other options. There is a “culture of hope” in medicine that can outlive its usefulness to patients.

The desire for better decision-making tools has lead to the creation of predictive software to give patients a evidence-based prediction of how likely IVF is to work for them in a future IVF cycle, based on their data from previous cycles and other personal health information relevant to fertility.

To complicate decision making, infertility treatments can become emotionally addictive with the patient becoming convinced that the very next treatment is destined to be successful. After all, we have suffered and spent so much. Well, unfortunately, it may not be. At some point, betting on futile treatments becomes damaging to patients. It does no good to finally accept that medical interventions are futile, decide to adopt and find that you have bankrupted yourself and now can’t afford to adopt or are considered too old to adopt a newborn or even a young child. I have seen it happen and I don’t want it to happen to you.

There are many support groups on-line that offer opportunities to find other people struggling with whether to stop or continue infertility treatments. You are not alone. RESOLVE offers one list of options here.  Google “upport groups childless living” or “support groups infertility” to find many others. If you are undergoing treatment, continually reassess where you are in the big picture and what you want your life to look like in 5 years, 10 years or 20. You may be surprised to see your answers change as your experience grows.  That’s okay. There are lots of paths to parenting and to living a full, rich life- with or without children. That would be the final stage, “shifting your focus”.  Bon Voyage.

© 2013, Carole. All rights reserved.

Original article: Are you addicted to IVF?

©2013 Fertility Lab Insider. All Rights Reserved.

1. Look up the success rates for the clinics that interest you. You can find them here at the Society for Assisted Reproductive Technology (SART) webpage.  You might miss a few clinics if your clinic is not a SART member. For those, look up results directly on the Centers for Disease Control (CDC) webpage.  Now compare their rate to the National Summary Report for the same year. This is the AVERAGE results for all clinics in the US, segregated by age of the female patients. Unless you have no other options, don’t go to a program that has less than the average success rate. Just don’t. I have heard lots of excuses for suboptimal performance. It is all BS.The labs I directed in Indiana and Pittsburgh easily achieved above average results every year because we knew how to do IVF. We hired good lab people and trained them well. Our docs could do a good stim and transfer an embryo properly. It wasn’t rocket science. The only downside to  reviewing the CDC and SART data is that it is two years old always so be sure to follow up and ask for current not-yet-published rates to make sure the clinic hasn’t taken a nosedive since the last official report.

2. Interview the program directly .

Find out how patients are “managed” in the clinic. Will you meet with the doctor or nurse at each appointment? Who calls you back to provide instructions, set up appointments or give you results? How easy is it to get in touch with the doctor, nursing staff or lab after hours if you have a question or concern? Do clinic staff answer emails or send text messages?  Keep in mind that there is no “right” way to handle any of this, but some methods may be more comfortable for you. Some people (patients and providers)  love the greater internet connectedness, others hate it and prefer a “face to face” or even phone conversation.

Ask about costs. You should receive a written estimate of all the expected charges for your treatment plan and also if you have insurance, how much will be covered and how much is your responsibility. Keep in mind that sometimes your IVF “team” is composed of different business entities. Your ultrasounds may be performed and billed by a different company than your clinic. Lab may be billed from a different company than the physician fees. Anesthesia is often handled by a separate company. Make sure you ask about ALL the parts of your care. Ask if all IVF fees must be paid up before you start treatment or whether you can make installment payments. Ask about any cash or other discounts that may be offered to you. Sometimes clinics offer discounts to patients in the military or public service sector. Ask about your anticipated cost of medications, realizing that if your ovarian stimulation response is weaker than expected, it may cost more. Two pharma companies, Serono and Ferring,  still offer discounts on ovarian stimulation medications. Serono offers different discounts for self-pay patients and privately insured patients. Ferring offers discounts through their HEART program.

3. Interview the program indirectly.

What are other patients saying about the program? There are lots of patient support groups on the internet which you can join anonymously and post questions. You can ask for respondents to reply to you privately to get the most honest feedback. Here are links to some of the best-known support groups :RESOLVE and INCIID.  Some lesser known support groups are listed on this webpage. You can find local chapters for many of these if you want face-to-face meet-ups. The key is getting feedback from lots of sources and looking for common themes.

Look for physician reviews.  Even Angies list now has a section for physician reviews where patients can describe their experiences with a specific provider. Keep in mind that most reviewers usually take the time and trouble to write a review if they are either exceedingly happy or unhappy with the service they received. What is telling in these reviews is common themes like long wait times or feeling rushed at the encounter which may be significant to you.  Ask people you know what they liked best and least about their program or doctor. keep in mind that most patients can forgive almost everything if they brought a baby home.

Google your doctor’s name. You might be surprised (and horrified) by what comes up. I have found news articles about law suits pending in other states or FDA warning letters regarding non-compliance. If your doctor seems to move around a lot from state to state or clinic to clinic, there might be a reason that has nothing to do with restless feet.

4. Use both your mind and your gut to analyze what you find. If your gut is still uneasy even if the doctor “seems so nice”, listen to your gut. Likewise, if he has a “Dr. House”-like bedside manner (meaning no bed-side manner) consider putting up with it if his results are stellar. When you visit the clinic, listen for signals that the staff is miserable, stressed-out or experiencing lots of staff turn-over. That is a really bad sign.  If the team doesn’t function well, the odds of your care being above average, let alone exceptional, go way down. You need to trust and respect your IVF team to do what is best for you and do it well. They need to be able to interact well with and respect each other for that to happen. You deserve nothing less.

© 2013, Carole. All rights reserved.

Original article: Finding your “Best Fit” IVF Program

©2013 Fertility Lab Insider. All Rights Reserved.

How they made a human clone:

1. Remove the nucleus (which contains  the DNA) from a human donated egg. The de-nucleated egg is now a sac filled with cytoplasm but no DNA. ( I expect there may be mitochondrial DNA from the egg donor but this is present as less than 1% of the DNA.)

2. Remove nucleus from another cell (in this case, a fibroblast type cell) obtained  from another person. Fibroblasts are a somatic cell type that gives rise to skin, for example.  For therapeutic cloning, the DNA for the clone comes from a patient who needs stem cell therapy. The clone that is produced is therefore a clone of the patient and has the patient’s DNA.

3. Transfer the DNA nucleus from the patient’s somatic cell (the fibroblast) to the  empty (no nucleus) donor egg using electrofusion, injection or other procedure.  The name for this procedure is Somatic Cell Nuclear Transfer, abbreviated SCNT in photo above.

4. The resulting embryo is cultured to the blastocyst stage. At this stage, in theory, it could be transferred to a human uterus to produce a human child, with DNA identical to the person who donated the fibroblast DNA.  That would be reproductive cloning.

5. For therapeutic cloning, the cloned embryo is dissected and the inner cell mass is removed, disaggregated and cultured further to produce stem cell lines (NT-ESC , Nuclear transfer – Embryonic stem cells) for all the cell types in the body. The cell type that needs repair (in the original donor) patient can be put to use to treat the patient. Because the new stem cells are made from the patient’s own DNA, tissue rejection is not an issue.

So what’s not to love with this approach? Patients get custom stem cells made for them to repair their hearts, their livers, or whatever organ is gone or going, and no human embryo produced in an IVF clinic (and otherwise meant to be a baby) was harmed.

But of course, it’s never that easy. Here are some of the concerns raised to date:

1. Slippery slope argument: Now that human cloning is technically feasible, it will be used for reproductive cloning, not just therapeutic cloning. First, reproductive cloning is illegal in most countries and most US states. Federal research dollars can’t be used to do reproductive cloning, so there are several barriers already in place to inhibit reproductive cloning. Some are calling for more restrictions. The other thing is that we don’t know how safe reproductive cloning is for the children produced. Since the early genetic imprinting is not through the normal pathways after fertilization, does this set the child up for health problems, possibly even cancer, down the road? There’s a lot we’d want to know first but whether anyone could ever legally (or ethically) do the research is questionable. The lead author of the paper, Masahito Tachibana, has stated that the next paper will explain why their approach will not work for reproductive cloning.

Some of the same concerns exist for therapeutic cloning. Can we be sure that the embryonic stem cells produced from a clone are normal enough not to give rise to health problems (even cancer) after they are injected into the patient?

2. Baby selling argument: Eggs are purchased from donors. We already pay donors for sperm and compensate egg donors for their time and trouble so it is not unprecedented. Also, eggs are not embryos and so egg selling. in my opinion,  is not akin to baby selling.

3. Pro-life argument: Any human embryo produced should only be used to make a baby (every embryo is sacred) and should not be destroyed/used for any other purpose. Human embryos should never be used as “parts” for therapy. The purpose or value of human embryos is what is at debate here. I can value human embryos and still believe it is okay to use them for an “alternative higher purpose” such as stem cell research or therapy. Others do not see this as an ethical option. The debate continues.

References and other articles about this scientific advance:

Cloning, Stem Cells Long Mired In Legislative Gridlock (NPR)

Cloning Is Used to Create Embryonic Stem Cells (New York Times) 

Patient-Specific Human Embryonic Stem Cells Created by Cloning (Scientific American)

Cloning FAQs page, National Genomic Research Institute

Original Paper: Human Embryonic Stem Cells Derived by Somatic Cell Nuclear Transfer (Cell)

© 2013, Carole. All rights reserved.

Original article: Scientific Advance: Human cloning for therapeutic use

©2013 Fertility Lab Insider. All Rights Reserved.

If you have a medical problem and can’t get pregnant, your odds of pregnancy become excellent if you can go to a high quality IVF program and avail yourself of a diagnostic work up followed up by one or more of these: superovulation with intercourse or insemination, IVF with or without ICSI, donor egg, donor sperm, donor embryo, or use of a gestational surrogate. Some combination of the above will solve pretty much everyone’s infertility depending on how far you are willing to go with technical interventions. It’s perfectly fine to draw the line at some point and say, Okay, that’s enough for me. I don’t feel comfortable with “fill in the blank”. That’s not unfair or unreasonable. What is unfair and unreasonable is when technical interventions you want are not available to you because you can’t afford them. That’s financial infertility. My international readers can tune out here because many of them have national healthcare that includes infertility treatment. Most of the people in the US don’t have an infertility insurance.

So what are you going to do about that? Nothing? How’s that working out for you?

Last Wednesday was Resolve’s National Advocacy Day, and lots of people affected by infertility went to DC to encourage our legislators to consider working on legislation to make infertility treatment accessible to everyone.  You can follow Tweets from Advocacy Day. There was a lot of excitement and Resolve advocates were able to encourage Rep. John Lewis (GA) to reintroduce the Family Act into the US House as bill HR 1851. From Resolve, here is a description of the Bill:

“The Family Act (S 881/HR 1851) creates a tax credit for individuals who have been diagnosed as infertile by a licensed physician and undergo in-vitro fertilization (IVF).  This bill will cover medical procedures, prescription medications, professional charges, the transfer of embryo and other necessary costs when a taxpayer undergoes in-vitro fertilization treatments. The Family Act also covers the out-of-pocket costs of fertility preservation if the woman or man has cancer or another disease that will render them sterile.”

There’s already a tax credit for adoption. This offers a tax credit for infertility treatments too which again, seems only fair. A tax credit is much less than a covered benefit but it is a start. Of course, if you can’t afford to pay the fees upfront, a tax credit on your expenses doesn’t help you at all.

I know times are hard and the drum beat of reducing government spending goes on. But here is the bottom line. THE GOVERNMENT WILL SPEND OUR TAX DOLLARS. THE ISSUE IS NOT WILL MONEY BE SPENT, THE ISSUE IS HOW WILL THE MONEY BE SPENT ? The government will fund its priorities. It’s your job as the people to let the government know what YOUR priorities are.

If you are still listening, here are some of the things you can do:

Resolve’s Take Action Page shows pending legislation and steps to get your legislators’ attention.

Ever wonder where your state ranked as far as being Infertility Friendly? Check it out here on this Fertility Scorecard on the map of the US.

Go to the Fertility Within Reach Advocacy Page to Empower Yourself  and “cure” yourself of financial infertility.HFind step by step advice on how to talk to your HR department about including infertility as a benefit in your insurance plan, how to talk to your legislator or your insurance provider. There’s even advice on how to talk to your doctor about a better deal. Your doctor may offer payment plans or discounts you don’t know about.

Your local Resolve Chapter support group may be organizing for action. If not, you can suggest ways to get moving in that chapter or start a new chapter.

Once you decide to get involved, there are lots of resources and groups to join with to advocate. But deciding that you are finally mad enough to get involved is the first step.

© 2013, Carole. All rights reserved.

Original article: You have survived another child-less Mother’s Day, now what?

©2013 Fertility Lab Insider. All Rights Reserved.

The blog started as an accident. I started Fertility Lab Insider in the months after I was “downsized” out of a job and replaced with a cheaper off-site consultant. I was devastated because I loved the people I worked with. At the time, I didn’t feel I could uproot my family yet again to move across the country and find another position. There aren’t a lot of IVF lab director jobs in any one city so moving or changing fields is often the choice a lab director has to make.  Reaching out to patients through the blog and explaining the work I did and loved as an embryologist was balm to my soul and helped me keep doing what I loved- although in a different way.

Over time, I gave more thought to effective communication because I realized from reader’s comments/questions that I wasn’t always clear. How can I communicate more effectively through my blog?  Some posts are better than others. Some posts are simply too long or too technical to be effective. I am still a work in progress on that front. Usually my Mom lets me know if I am too technical. My husband lets me know if my blog is too long- “split that post into 3 parts!”  

I think effective patient education is so very important because I think it leads directly to patient empowerment which leads directly to better outcomes. But effective communication is hard.  It is not easy to communicate clearly with patients, particularly when they are struggling with infertility -which is not only physically but emotionally difficult.  As embryologists (or nurses or doctors) , we need to remember that although we have said the same clinical message a thousand times before, each patient is hearing the message for the first time. It’s never old for them. It is a good thing for me to improve my communication as a blogger- but it is critically important in the clinic and can make the difference between cycle success and failure.

So, how can health care providers in the clinic (doctor, nurse and embryologists) do a better job of communicating with patients?

I’d like you to help me answer that question. You are experts at what good communication (or poor) communication looks like because you are at the receiving end. I need your help on a research project I am doing. To celebrate my blogaversary, I decided to look at the three years of data for Fertility Lab Insider based on Word Press statistics and also use Google Analytics data to try to understand which lab topics elicit the most comments or questions. I have done that and found some interesting trends in top landing pages and so forth. But I think it would be especially valuable to ask you directly about your healthcare communication experience with your IVF doctor, your clinic or your embryologist. So here’s your chance to give your feedback about what communication methods/styles worked for you and what didn’t.

As always, I welcome feedback on the blog- good or bad -and feel free to comment on this too  because I’d want to make the blog better.  But hopefully- your healthcare provider is your primary source of medical information for your case and so that is where good communication is most important- and that is a more important topic for research.

So here are some of the things I’d like to know about your experience with health care communication and how it helped or hurt your treatment outcome. Please don’t identify anyone by name.  Comment anonymously or with a pseudonym. If I include your actual comment in a presentation of the responses, I will not use your name.

Here are some questions to consider regarding effective communication methods– but feel free to comment outside of these questions. Part of the problem with effective communication is also understanding what questions someone else may have. (I am currently teaching my teenager to drive and I have found that understanding what they don’t know is a critical first step!! I think that may apply here too so if these questions are poor or irrelevant- substitute your own).  Answer one or more of these or just put in your two cents. Use the comment box or email me privately. I am listening.

• What lab topics are of most interest to you?
• Who was your primary communicator for lab info?- your doctor, your nurse, or lab staff?
• Was there anything about your clinic’s communication with you that was exceptionally good- or exceptionally bad?
• Did you feel that you had all your lab questions answered?
• Was your health care provider pleased/annoyed/disappointed when you asked for more information about lab topics?
• Did you want more or less lab information than you received- give an example.
• Why do you end up looking for more information on this blog? Was it to get primary info, to add to what you get from the clinic, or to verify the info from the clinic?

I hope that you will ALL participate. Everyone has experiences here that could help others.  I will summarize the comments and blog stats in a future post. Thanks!!!

© 2013, Carole. All rights reserved.

Original article: Is your doctor/embryologist/nurse a good communicator? Why or why not?

©2013 Fertility Lab Insider. All Rights Reserved.

So what does this have to do with National Infertility Awareness Week? Nothing and everything. At times like this, we tend to reevaluate what is important to us –since life is shorter than we think- maybe much shorter than we think. We automatically hug our kids, our lovers, our parents, our siblings and friends tighter. The fragile emotional bonds between us make our lives rich with meaning.

If you want children and can’t have them for medical reasons, that creates a hole in the fabric of your life, precisely because these bonds are so precious. Now, I am not saying that these bonds can’t be just as precious between ourselves and other people who are critically important to us–but if you want children and can’t have them- that is a big deal. It is not just a social choice, it is a medical right to have access to infertility treatments.

I have been researching the barriers that infertility patients encounter to gain access to infertility treatments and the results have been illuminating.  Financial and social issues are the two biggest barriers and they are linked. Various studies have shown that there exists a social bias against single women, older women, lesbian women and women with disabilities, who are deemed somehow less deserving of extraordinary measures to become pregnant. Women in minority groups, particularly if they are poor are also more likely not to have access to infertility treatments. They may not even be offered treatment because IVF is considered too expensive for them. Under the current system, it often is. If you are in one of these groups- or simply don’t have the cash to pay for IVF- you are less likely to have access to infertility treatments. In some cases, it is because physicians elect not to provide care to these groups because of personal “values” about who should be a mother. In other cases, it is because insurance companies have decided to exclude certain groups (gay, single or older women) from their policies.

Society has done a poor job of supporting infertile people. The knee jerk reaction is often “Just Adopt’! which is bad advice for several reasons. First, adoption is not a good choice for everyone who wants to have a family. Second, adoption is hard to qualify for and expensive. The same groups of people who are excluded from infertility treatments (older, single, LGBT etc. ) are likewise often excluded from adoption due to discriminatory adoption agencies policies. Finally, it is pretty nervy to assign this problem of homeless kids solely to infertile people to solve. Unless you have already adopted a child, refrain from telling someone else to “Just Adopt”.  It just makes you look stupid.

So what does this mean? It means, currently, with the exception of a few islands of help,  you are on your own in figuring out how to get access to high quality infertility treatments. This could change if public perception of the infertility problem becomes more realistic (with less Octomom tabloid coverage and more education about causes and treatments). This could change if insurance policies and even  health initiatives like the Affordable Care Act would redefine infertility care as an essential medical benefit- like cancer treatment or setting a bone. Studies have shown that the emotional and psychological toll of infertility diagnosis and treatments can be as devastating as the diagnosis and treatments for cancer. The fact that infertility is not trivial is not fully appreciated. Education can change that. Advocacy can change that.

So about those islands of help… One of those islands is a small but growing non-profit, called Fertility Within Reach, (incidentally, located  in the Boston area), whose mission is to help people help themselves to get the infertility treatments they need. Sometimes you just have to know how to ask for something to get the help you need from your doctor, from your HR department, from your insurance plan or from your legislator. Fertility Within Reach has created patient toolkits to help you advocate more successfully  for yourself. You can download action checklists from the site. You can read about patient success stories on their site. Hopefully, you will come away feeling empowered.

I am working to find dollars to pay for the educational outreach that Fertility Within Reach offers in the form of  free tool kits that are available on their website. We are planning a webinar series in the Fall if we can find funding. If desired, Fertility Within Reach also offers one-on-one coaching for patients to guide them through navigating insurance etc. As I apply for grants from foundations that support women’s health issues,  I am running into the same problem with multiple foundations that you would think–based on their websites– would support infertility access as part of the bigger picture of women’s health. They say that they support women’s health and reproductive health initiatives but that does not mean they are sympathetic to or willing to support people with infertility. They will support contraception and abortion but not infertility. I still haven’t figured out how to extend their empathy (and dollars) toward programs to help infertility patients get access to care. So I am working on communicating better with these agencies.

So foundations, insurers and government programs aren’t yet rushing to pull down the fences to provide access to infertility treatments for people that need it.  But we can. Fertility Within Reach has partnered with See your Impact.org, to raise funds to support their programs during National Infertility Awareness Week which is next week (April 21-27). I have asked my colleagues, friends and family to support this initiative. Now I am extending this request to you to help other members of the infertility community. If you can give even $5 or $10, you can make a difference.

Next week for National Infertility Awareness Week, please check out Fertility Within Reach and if you can, send them a donation at my See Your Impact fundraiser page. I am hopeful for better days next week. Peace.

© 2013, Carole. All rights reserved.

Original article: National Infertility Awareness Week 2013

©2013 Fertility Lab Insider. All Rights Reserved.

1) they were able to recover embryo DNA from the fluid-filled center (the blastocoel) of blastocyst stage embryos and

2) they were able to amplify the DNA sample to determine the gender of the embryo and in some cases whether the embryo had abnormal chromosome numbers (aneuploidy).

This is exciting because it’s the first time that the blastocoel fluid has been found to contain at least fragments of DNA–which might be a good source of DNA for genetic analysis for preimplantation genetic screening (PGS) or preimplantation genetic diagnosis (PGD). PGS is a method for testing embryos for chromosome number abnormalities and for determining gender. PGD is a method for testing embryos for genetic sequence abnormalities (mutations) giving rise to genetic diseases or conditions. When abnormal embryo are determined, they can be preferentially excluded from transfer.

Currently, technicians perform embryo biopsy on each embryo to be tested. Technicians need to carefully remove one or more cells from the embryo to recover DNA for testing, which is tricky and if done poorly, can damage the embryo. In a day 3 eight cell embryo, taking 1-2 cells may result in slightly slowed progression as the embryo has very few cells to begin with and is at a delicate stage of development. It is technically simpler, quicker and perhaps more kind to the embryo to insert an ICSI needle into the middle of a blastocyst and remove some fluid, compared to carefully pulling off a small number of cells.

Basically, this needle stick into the blastocoel is a routine measure done currently to temporarily deflate or collapse the blastocyst before vtrification for optimal freezing results. It would  take relatively less skill and only a little training beyond that needed for ICSI for most technicians to become proficient at this technique. If it were this easy to get good DNA for genetic testing, that would definitely improve the technique for sampling. But is the quality of DNA what is required to get good reliable test results?

There are a lot of questions yet to be answered.  Jacques Cohen, master of micromanipulation techniques and his colleagues (Gedis Grudzinskas, Martin H. Johnson), do a good job of outlining the questions that still need to be answered before we all get too excited about this possible replacement for biopsy in this article-in-press editorial, “Embryonic DNA sampling without biopsy: the beginnings of non-invasive PGD?” This editorial can be accessed from the RBO site for free; the actual research findings paper -in the same issue -requires payment to read more than the abstract.

Here are the main challenges to be overcome as put forth by Jacques Cohen and colleagues,  (copied below):

1. “Does the procedure sample DNA that is representative of the embryo? Control samples were obtained from the culture droplets, but it is known that human DNA is often present in embryo-free droplets of protein-supplemented culture medium. A follow-up trophectoderm biopsy was not performed, but this is an obvious second series of experiments to compare cell-free DNA results with those from biopsies.
2.  Could the DNA have been released from abnormal or degenerate cells that are often excluded from the embryo? If so, the DNA may not always be representative of intact cells from the embryo.
3. Is the procedure truly non-invasive? Whereas the procedure may not extract cells, damage may occur during the manipulation process possibly affecting the viability of the blastocyst.
4. Can it be proven that the piercing of the trophectoderm and suction of fluid does not inadvertently release cellular material from the blastocyst, which is then aspirated and analyzed? The authors exclude this alternative explanation theoretically, and they may well be correct, yet the assumption needs to be proven.
5. If DNA is dislodged into the blastocoel, can it also be released through the pores in the zona pellucida into the immediate environment?
6. If affirmative, can the procedure be implemented by culturing blastocysts in minimal volumes to sample the products externally without micromanipulation? Can such sampling be done before blastocyst formation?”

In any case, it is an interesting initial finding and if further validated may refine and make safer current DNA sampling methods for PGD or PGS.

© 2013, Carole. All rights reserved.

Original article: Blastocoel fluid as a DNA source for PGD/PGS

©2013 Fertility Lab Insider. All Rights Reserved.

To understand this, it is important to consider the problem of childhood cancers. We are getting better at curing childhood cancers so that the life expectancy for some survivors of childhood cancers is well into adulthood and even old age. This increasing longevity makes one of the possible side-effects of life saving chemo and radiation therapies-namely, sterility–a quality of life issue. Although some cancer survivors can recover some or most of their sperm production ability, other male survivors are irreversibly sterile after treatment. It is not possible to exactly predict in which category a person may find themselves in the future. The type of cancer and intensity of the treatment used both affect the probability of becoming sterile.  For teenage boys who have gone through puberty and adult men, it is possible to collect one or more ejaculates before cancer treatment, and freeze and store these samples for future use, as a sort of “insurance policy”  against sterility.  For pre-pubertal boys, this is not an option because they aren’t producing sperm yet.

But pre-pubertal boys have lots of testicular stem cells called spermatagonial stem cells (SSC) which could in theory, be likewise recovered and saved  before cancer treatment and returned to the testicles later to repopulate the testicular tissue with sperm-producing cells.

SSC are the renewing stem cells whose job is to replicate themselves so that there is a continual stem cell supply (see Type Ad Spermatogonium (the blue cells) in a renewal cycle below). Not all stem cells replicate themselves. Some commit themselves to a differentiation pathway that ultimately results in the mature sperm cell (right handed pathway- with multi-colored cells). 

There are multiple steps after the secondary spermatocyte stage. The spermatocyte cell loses its round cell shape and begins to look like a sperm  in a process called spermiogenesis.  The cell elongates, gets a tail, puts it mitochondria behind the sperm head, loses excess cytoplasm, encapsulates the DNA in a proper sperm head etc. At puberty, some of the stem cells spring into action and start making sperm. A helper cell in the testis called the Sertoli cell (shown as the pinkish cells studded with blue spermatocytes- the smaller figure above) serves as a sort of docking station through which the spermatocytes pass as they morph into a proper sperm cell.

So how would gonadal cell stem cell transplantation work?

Step One: Under anesthesia, take a testicular biopsy. Freeze the biopsy and store for future use.

Step Two: Thaw tissue sample when the patient is in remission and is ready to start a family.

Step Three:  Inject a suspension of thawed testicular cells containing stem cells into the rete testis of the patient, where hopefully the stem cells will seed and re-activate to produce more of themselves and then many, many sperm cells.

Other proposed fertility preservation options using stem cells which one day may have clinical applications include:

• Grafting testicular tissue back into the testis. Tissue could be derived from frozen/thawed specimen or possibly donor tissue.
• Putting testicular stem cells in culture and growing out sperm cells from these stem cells in a dish. The number of sperm produced would likely be enough only for IVF or ICSI, not uterine insemination.
• Make more stem cells-and then sperm- from non-gonadal cells, by reverse engineering the pathway from more differentiated to less differentiated (stem cell)  and then committing the stem cell to make a more differentiated (sperm cell). Sperm was produced from embryonic stem cells (and in another experiment, fibroblast cells) in the mouse by first making induced testicular stem cells and then making those newly derived stem cells into sperm. These sperm were used to make mouse pups.

Hurdles to these approaches are not insignificant.

• We do not presently have a good method to propagate or amplify the rare stem cell recovered from a patient’s testis into significantly more stem cells in vitro. We also want to be certain that when these cells divide in culture that they remain”true” to the original copy and aren’t introducing genetic mutations because they are more unstable than “wild type” cells. We need to understand stem cells better.
• There is always a possibility when removing cells from a cancer patient, that you recover some contaminating cancer cells along with the normal healthy cells, even if the cancer is not in the testicle. If it is in the blood, there is some theoretical risk of transplanting the cancer. This would obviously be a catastrophe. We must figure out ways to minimize this risk but we are not there yet.
• If all the technical barriers were overcome, and it works, and we have babies born from these stem-cell transplant procedures, what assurances could we have that children born from these procedures will be as healthy as children in the rest of the population? Obviously, at the very least, we would want to do many generations of studies in animals first.

So although there is a long way to go, stem cell transplantation is a real area of research, not a hoax. Someday, it may even be a standard clinical procedure for fertility preservation in the pre-pubertal male who is at risk of sterility due to cancer treatment.

© 2013, Carole. All rights reserved.

Original article: Q from U: Is testicular stem cell transplantation real or a hoax?

©2013 Fertility Lab Insider. All Rights Reserved.

Highlights of IVF as viewed through the career of Robert Edwards (summarized from the paper by Martin H Johnson, entitled Robert Edwards: the path towards IVF)

1925: Born in Yorkshire, England to a working class family. Passed special exam to attend Manchester Central Boy’s High School.

1945: Began university education but was interrupted by WWII

1951: Continued at University College of North Wales at Bangor, initially for agriculture, but then switched to more appealing Zoology. Surprisingly, he graduated with only a pass, without honors, which was very personally upsetting at the time.

1951: Was accepted at Edinburgh in a post-grad Diploma course in Animal Genetics; began intra-disciplinary research in Developmental Biology in the mouse model. Published 14 papers here, largely on sperm-related topics. Egg biology was more difficult to research due to lack of research material- namely mouse eggs. He mastered superovulation of the mouse in order to get sufficient eggs for his research. Superovulation with gonadotropins is critical to  IVF so this basic work was one of the stepping stones to human IVF.  During his time at Edinburgh, the work he did resulted in 38 papers, so many that some were not even published until 1963.

1957-1958: Worked at the California Institute of Technology in the US studying sperm-egg interactions. He became interested in reproductive immunology, particularly how the mother’s uterus was able to accept rather than reject an embryo that was half foreign (due to 50% paternal contribution).  Although he considered this time a “holiday” of sort, he published 23 papers from work he did in this area.

1958: Returned to the UK to work on the science of immuno-contraception, but was ultimately more interested in the mysteries of the egg, egg maturation and fertilization. He was interested how the egg could have problems during meiosis called non-disjunction events or lagging chromosomes which could result in an abnormal number of chromosomes (aneuploidy). Aneuploidy is a significant issue for older women and interferes with successful IVF outcomes.

1960-1962:  Edwards worked with a gynecologist to get ovarian biopsy tissue, recovered eggs for the tissue and noted that they seemed to spontaneously mature in vitro when released from the follicle. This phenomenon of spontaneous maturation, although encouraged by administration of hCG a few days before retrieval,  allows eggs to be combined with sperm after only a few hours post-retrieval.  Although encouraging, his work on human IVF using human eggs from ovarian tissue was banned by the director of the Institute, abruptly ending his progress toward clinical IVF for a time.

1965-1966: He published papers in which he showed that he could derive embryonic stem cells(ESC)  from rabbit embryos by dissecting the intercellular cell mass and growing the cells in vitro. This work was largely ignored for the better part of 20 years until two other researchers (Evans and Kaufman) demonstrated that ESC’s could be derived from mouse embryos in 1981. Edwards was a little too advanced in his ESC production and so his seminal ESC work failed to be appreciated for over twenty years.

1963: Moved to Cambridge as a Ford Foundation Research Fellow. For the next several years, he continued his efforts to understand egg maturation and the kinetics of chromosomal sorting that occur during meiosis. Mishaps with chromosomal sorting result in aneuploidy. He developed the “production line theory” of egg maturation to explain the increased occurrence of aneuploidy with increasing maternal age. In 1965, he reached out to Howard and Georgeanna Jones, IVF pioneers who opened the first US IVF Clinic and who provided him with sufficient human eggs to confirm his egg maturation theories in the human. This also started a long-lasting collaboration between Edwards and the Jones’s.

In this interesting interview with the now-deceased Howard Jones, he discusses his belief that he and Edwards may have actually fertilized a human egg in 1965 while Howard was still at John Hopkins, but they weren’t sure because they could not detect a sperm tail, just two pronuclei. Today we know that two nuclei is considered ample evidence of fertilization in humans. An intact sperm tail is rarely observed. (In 1979, a year after Louise Brown’s birth in England, Georgeanna and Howard Jones “retired” from John Hopkins and opened up the first US IVF clinic, the Jones Institute at Eastern Virginia Medical School.)

Wednesday 28 February 1968: Robert Edwards met Edward Steptoe, who had been a Consultant Obstetrician with a specialty in surgical laparoscopy at Oldham General Hospital since 1951. Steptoe’s interest in human IVF was treated with hostility by his colleagues and Edward’s was initially “warned off” contacting Steptoe. The earliest IVF egg retrievals were performed not with minimal invasive ultrasound-guided needle aspiration as is used today  but by opening up the abdomen. It was this surgical skill for egg removal for IVF that interested Edwards. Likewise, Steptoe found in Edwards, a life-long colleague, who shared his interest in human IVF. Together they would achieve the birth of the first IVF baby, Louise Brown, born in 1978,  ten years after this first meeting.

Another scientific problem holding back Edwards and Steptoe’s ambitions for human IVF was the problem of sperm capacitation. Sperm need to be exposed to the female reproductive tract fluids to become “capacitated”, the final step in sperm maturation so they are capable of fertilizing an egg. This sperm capacitation problem was solved when Robert Edwards encountered the work of Barry Bavister, who had just solved the problem of in-vitro capacitation in hamster sperm, by showing he could increase sperm fertilizing ability, simply by increasing the pH of the media.

December 1968:  Edwards, Bavister and Steptoe, submitted their landmark paper to the journal Nature, describing human IVF for the first time.  Previous papers by others had claimed success but this Nature paper was definitive.

1971: His 1968 IVF success was met with public distrust due to hostile media coverage of human IVF in Britain and his request for research funding was denied in the UK. Perhaps this was the first, but certainly not the last time that IVF research would be killed due to societal backlash, both in the UK and the US.

Edwards battled negative public perception of IVF and professional hostility from his colleagues for the better part of a decade. Some of his  colleagues considered human IVF a form of human experimentation, without merit. Treatment of infertility was not considered a societal good because human overpopulation was considered the overriding social ill and research to develop better population control was considered more worthy scientific work.

July 25, 1978: Louise Brown was born, and the social tide against human IVF began to turn. It is hard to deny the joy of new parents who have overcome infertility through the intervention of IVF. It was a long hard road for Edwards to see his life’s work culminate in joy for that first IVF patient. He was awarded the nobel prize in 2010 for his IVF work.

Robert Edward’s scientific work left a lasting mark on the world- for the better. Thank you, Sir Edwards.

© 2013, Carole. All rights reserved.

Original article: IVF Pioneer Robert Edwards died today (April 10, 2013).

©2013 Fertility Lab Insider. All Rights Reserved.

Below is an explanation about what the FDA regulates, copied from the FDA website. Although written with sperm donors in mind, egg donors are also included though some aspects of the regulations are modified (eg. testing interval before egg retrieval):

“What You Should Know – Reproductive Tissue Donation

11/5/10

Did you know that FDA regulates human reproductive tissue, which include donated eggs (oocytes) and sperm (semen)?  Below is information that you may want to know before becoming a recipient of donated sperm.

1) Is the establishment registered with the Food and Drug Administration (FDA)?

Donated reproductive tissue (eggs or sperm) are regulated as human cells, tissues, and cellular and tissue-based products (HCT/Ps).  Any establishment that performs one or more manufacturing steps for HCT/Ps (recovery, processing, storage, labeling, packaging or distribution of products) must register with FDA and list their HCT/Ps in accordance with Title 21 Code of Federal Regulations (CFR) Part 1271.

You can access information on registered HCT/P establishments by visiting our website.  The site includes the names of registered establishments, the products that they manufacture, and the manufacturing steps they perform. 

2) Are reproductive HCT/P donors required to be screened for risk factors that may increase the chances of transmitting a communicable disease?

Yes.  Donor screening consists of reviewing the donor’s relevant medical records for risk factors for, and clinical evidence of, relevant communicable disease agents and diseases.  These records include a current donor medical history interview to determine medical history and relevant social behavior, a current physical examination, and treatments related to medical conditions that may suggest the donor is at increased risk for a relevant communicable disease.

3) Are reproductive HCT/P donors required to be tested for infectious diseases?

Specimens from reproductive tissue donors must be tested for the following infectious diseases (referred to as “relevant communicable disease agents and diseases” in the regulations):

1. Human Immunodeficiency Virus (HIV), types 1 and 2 
2. Hepatitis B Virus (HBV) 
3. Hepatitis C Virus (HCV) 
4. Treponema pallidum (i.e. syphilis)
5. Chlamydia trachomatis
6. Neisseria gonorrhea

In addition to those listed above, sperm donors must also be tested for:

1. Human T-lymphotropic virus (HTLV), types I and II
2. Cytomegalovirus (CMV)

4) Are reproductive HCT/P establishments inspected by FDA?

Yes.  Various factors can determine the frequency of inspection, including any objectionable conditions found on a prior inspection and/or if FDA received Information regarding an establishment indicating there is a potential violation of FDA regulations. 

5) Where can I get more information?

Related information about the regulation HCT/Ps can be found on FDA’s website at:
http://www.fda.gov/BiologicsBloodVaccines/TissueTissueProducts/default.htm.”

Your IVF program, if they do IVF with donated gametes, must be able to prove that a donor was properly vetted and is eligible to donate.  It makes no difference if the program does one egg donor cycle a year or hundreds. They have to produce proof that they followed FDA regulations. Commercial sperm banks do the same for sperm they sell. It’s good for patients to know what the FDA expects and these public warning letters are useful for patients to recognize non-compliant clinics.

© 2013, Carole. All rights reserved.

Original article: FDA cracking down on non-compliant IVF programs

©2013 Fertility Lab Insider. All Rights Reserved.