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Archive for the ‘PGS/PGD’ Category

To Snip or Not to Snip…DNA Discoveries Making Science Fiction Fact

By David Kreiner MD

March 14th, 2017 at 1:04 pm

 

image purchased at shutterstock


Working in the field of In Vitro Fertilization (IVF) for over thirty years, I am in awe of the powerful potential our technology offers. Today Pre-Implantation Genetic Screening (PGS) is routinely offered to fertility patients undergoing IVF to test the chromosomes of embryos that a patient has created prior to Embryo Transfer.  If PGS shows a normal complement of chromosomes then a single embryo transferred has an approximate 50% chance of resulting in a pregnancy with a less than 10% chance of miscarriage.  As gender can be identified by this process, selection based on gender is available.

Many question the ethics of any manipulation of embryos including selecting the embryo for transfer based on gender.  Although I am not fond of those equating family balancing with genetic engineering, I do share their concern of clinical tampering with the DNA of embryos.

Technology in IVF is reaching the point where DNA may be snipped, removed and/or implanted.  Clinically, one can foresee where diseases and serious health conditions may be cured or prevented by such pre-embryo manipulations.  Though I am tempted to cure or eliminate disease and serious health conditions, I worry that when we snip to cure we may unknowingly create some new malady– perhaps of a nature we have not previously envisioned.

The Brave New World of Aldous Huxley may be upon us but whether you view this world as positive in its ability to give man the power to eliminate disease or negative because you fear that man in his limited knowledge is apt to cause unforeseen damage is based on your own individual perspective and it is society’s duty to control in a responsible way the utilization of this new technology.

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Do you see the power to eliminate disease by snipping, removing or implanting DNA as a positive or negative? Why?

 

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Fertility Awareness Opportunities Angelina Jolie Missed

By Tracey Minella

September 20th, 2016 at 10:11 pm

Public Domain Image: courtesy of publicdomainpictures.net/vera kratochvil-wax figures

 

[This post was originally posted in March, 2015. It's being reprinted as a reminder of what we can learn from the health care decisions Angelina Jolie bravely made and shared publicly.]

Actress, director, humanitarian, ambassador, mom of twins, adoptive mom, wife of Brad Pitt. And she’s gorgeous.

What’s not to hate?

Oh, I’m just sort of  kidding. No, really. But despite all the good she does, there will always be haters. People who want her money, her talent, her babies, or her man. Jealousy can do that.

I don’t admire many celebrities… and that’s fine, because their only job is to entertain me, not impress me. But I am impressed with Angelina Jolie. She’s charitable with her time and money and seems pretty grounded for a megastar. And she uses her celebrity for good.

It’s been only two years since Jolie made headlines for undergoing a preventative double mastectomy after testing positive for the BRCA gene mutation… a mutation that significantly increases the lifetime risk of getting breast cancer. At that time, she was open about her decision and used her celebrity to increase breast cancer awareness.

This week, Angelina revealed that she took those preventative measures to the next level. This time, she had both of her ovaries and fallopian tubes removed in the hope of avoiding ovarian cancer…another deadly cancer linked to the same gene mutation. Jolie lost her mom to ovarian cancer and said in a recent New York Times Op Ed piece that she doesn’t want her children to experience the same loss. Her openness is raising awareness of ovarian cancer.

But there is another untold story here, too…a fertility awareness story…and it needs to be heard.

Unless you’ve been hiding under a rock, you know Jolie has six children. She adopted three children internationally and gave birth to a singleton and a pair of twins. Practically eliminating her risk of getting ovarian cancer is not the only result of her surgery.

The media is reporting that she can no longer have biological children. And Jolie acknowledged how hard her decision would be for a woman who has not completed her family-building. Perhaps because of the size of her family, this point seemed lost on the general public. But it’s not lost on you, is it? This surgery is a big deal. And before others who may not be done with their family-building journeys emulate Jolie and follow her path, some crucial missing information needs to be shared.

In fact, there are three opportunities here to increase fertility awareness and educate the public about advances in the field of reproductive technologies, namely PGD, Egg donation, and Egg-freezing.

First, there’s pre-implantation genetic diagnosis (“PGD”). PGD enables couples who are concerned about passing a life-threatening genetic disease on to their children to have their embryos pre-screened for gene mutations. This screening can only be done in conjunction with an in-vitro fertilization (IVF) procedure, where eggs are retrieved and fertilized in a lab and the resulting embryos can be tested. Then, only those embryos that did not test positive for the mutated gene would be transferred into the uterus…virtually eliminating the chance of passing on that hereditary disease. BRCA is one of the many genes that can be screened through PGD. Long Island IVF offers PGD.

Second, there’s egg donation. If a woman has her ovaries and tubes removed, she cannot thereafter have a biological child…one created using her own eggs… however she may still experience childbirth. If she still has a healthy uterus, it may be possible for her, through IVF, to use eggs from an egg donor and the sperm of her partner or a donor, and have the resulting embryos transferred into her uterus where a pregnancy can implant and grow to term. Long Island IVF’s Donor Egg Program brought Long Island its First donor egg baby decades ago.

Finally, there’s the latest breakthrough in women’s fertility preservation technology: egg freezing. Egg-freezing offers an exception to the egg donor statement above. If… prior to removing her ovaries… a woman undergoes IVF for the purpose of either freezing her retrieved eggs (or freezing the embryos resulting from the fertilization of her retrieved eggs), then instead of needing donor eggs, she would be able to later have her own frozen eggs or embryos thawed and transferred into her uterus in the hope of becoming pregnant with her biological child. Or if her uterus was unsuitable or absent, she could still have a biological child by having someone else carry a pregnancy for her. (Note: Surrogacy and gestational carrier laws vary from state to state.) Long Island IVF has an Egg Freezing Program.

These three fertility awareness opportunities, when coupled with Jolie’s breast cancer and ovarian cancer awareness, will further empower women everywhere to make better medical choices and take charge of their fertility and general health.

Shame on the haters. It’s wonderful that Jolie is open about her health in a way that raises awareness for others. She is a just a mom. A selfless mom who just wants to be there to see her children and future grandchildren grow up.

Is there something wrong with being proactive after tests show you carry a gene that could one day take your life, like it took your mother’s? Are the haters just jealous of her? Is she a hero?

* ** * * * ******** *** * **

What do you think? What would you do?

 

 

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8 Things to #StartAsking and #KEEPAsking after #NIAW

By Tracey Minella

April 30th, 2016 at 4:43 pm

 

image courtesy of Resolve, the National Infertility Association


Honestly, my first reaction to this year’s NAIW #StartAsking theme wasn’t positive. It just didn’t sit right with me for some nagging reason I couldn’t put my finger on. So, it was hard to sit down and write a post using it. It made me have to really think about some serious and difficult things. Stuff I usually keep locked away. Some days, I just don’t have the strength to think too hard.

Start Asking.

Start Asking why? Start asking how? Start asking for something?

Start asking…what, exactly?

Should I start asking Why me? Truth be told, that was the first thing that came to mind. But there is no point in asking that question. So what is worth asking?

Then it dawned on me. We need to start asking for whatever it is we need in order to get through this journey (or to see that those who follow us can get through it). It’s that simple. And that difficult.

That means asking for help, for understanding, for respect, for answers, for kindness, for prayers, for coverage, and for action.

Start asking yourself what you need. And who can fill that need?

  1. Help: It’s hard to ask for financial help but if it’s the only barrier to treatment, you may have to ask. Loans, gifts, online fundraising sites are some ways to finance fertility treatment. Most IVF practices offer grants as well. Ask for help.
  2. Understanding: No one will truly get it unless they’ve battled infertility themselves. But they need to try to understand why it’s too hard for you to handle things like baby showers, egg hunts, and gender reveal parties for a couple’s 5th baby. Tell them you’re happy for them, but it hurts too much to participate right now. Ask them to understand.
  3. Respect: Everyone has advice on how you should be handling your infertility journey. Regardless of their personal (and usually uneducated) opinions, they need to respect the decisions you’re making…whether that involves IUI,  IVF, egg donation, donor sperm, surrogacy, egg freezing, pre-implantation genetic screening, adoption, or choosing to live child-free. Ask them to respect your right to make your own decisions.
  4. Answers: There is no such thing as a stupid question, at least when it comes to infertility treatment. So much is on the line that you owe it to yourself to understand the often complicated and ever-changing world of assisted reproductive technology. Understand what is happening to your body during any given treatment or procedure, including the medications you’re taking, how to take them, and any possible side-effects.  Knowledge is power. Ask questions if you don’t understand something.
  5. Kindness: Similar to respect, you deserve to be treated kindly. People can be mean…on purpose or innocently. “Why can’t you give me grandchildren?” “He just looks at me and I get pregnant”. “You can have one of mine.” “I’ll get her pregnant for you”. “Be thankful you have one.” Protect your heart. Ask people to stop saying hurtful things like that.
  6. Prayers: For the religious, infertility (especially a long journey filled with losses) can sometimes be a test of one’s faith. Don’t feel guilty asking why this is happening to you or questioning why your prayers are not being answered. If your faith is a source of comfort and strength to you and also to those you know, ask for their prayers or good thoughts on your behalf.
  7. Coverage: As you no doubt know, the biggest barrier to infertility treatment is often lack of health insurance coverage. Most policies offer little to no coverage for fertility treatments like IVF. The only hope for change lies in advocating for new legislation mandating better infertility coverage. Ask your elected representatives to create or support legislation mandating IVF coverage.
  8. Action: Start asking is a good start. It’s a catchy theme for NIAW. It’s good to raise awareness. One week per year. But that’s not enough. We need infertility action not just infertility awareness. The week is over. Tomorrow we risk being forgotten until next April (or at least until we resurrect Coming Out Infertile Day in November). And those baby shower invites will still flood the mailbox. Those nagging personal questions will not abate. And those uncovered infertility costs will still prevent many from accessing the treatments they need to become parents. Ask yourself and others to take action for real change.

I guess my issue with the theme this year, or maybe every year, is just a frustration over the slow pace of change. And the poor collective memory of the public. Tomorrow will not only start a new week, but a new month. A new “awareness” cause to push. By Friday, will anyone still be aware of infertility? Will they still be ASKING? We don’t need to just #StartAsking. We need to #KEEPAsking.

Let’s show our appreciation for –and join–all the tireless infertility advocates who support the infertile folks of today through activism, advocacy, blogging, and more. To the extent you can, join the fight. Consider participating in Advocacy Day . Don’t just start asking. Keep asking. Then keep acting until real change happens. Until we have babies for all.

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What did you #StartAsking? What will you #KeepAsking?

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Long Island IVF-WINNER: Best in Vitro Fertility Practice 2015 AND 2016

It is with humble yet excited hearts that we announce that Long Island IVF was voted the Best In Vitro Fertility Practice in the Best Of Long Island 2015 and 2016 contest…two years in a row!

The doctors, nurses, embryologists, and the rest of the Long Island IVF staff are so proud of this honor and so thankful to every one of you who took the time to vote. From the moms juggling LIIVF babies… to the dads coaching LIIVF teens…to the parents sending LIIVF adults off to college or down the aisles… to the LIIVF patients still on their journeys to parenthood who are confident in the care they’re receiving…we thank you all.

We love what we’ve gotten to do every day more than 28 years…build families. If you are having trouble conceiving, please call us. Many of our nurses and staff were also our patients, so we really do understand what you’re going through. And we’d like to help. 631-752-0606.

 

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IVF and Comprehensive Chromosomal Screening (CCS) a/k/a Pre-embryo Genetic Screening (PGS)

By David Kreiner MD

January 20th, 2016 at 1:55 pm

 

credit T. Minella

In 1985, when I started my fellowship training at the Jones Institute, IVF technology was so new that we numbered each baby that was born as a result of IVF and it was still in double digits. People came to us for IVF from all over the world because our success rate was the best — at that time, just 15 percent.

The technology of IVF was so inefficient then, it was routine to transfer six embryos at a time. That’s what it typically took to create a singleton pregnancy. Sometimes the result was multiples. My experience with multiple pregnancies in those early years opened my eyes and heart to the additional struggles that accompanied patients’ tremendous joy at finally being pregnant.

With the discoveries and improvements in both clinical and laboratory procedures and techniques in the early 2000’s, success rates for IVF boomed… allowing for the transfer of a much more limited number of embryos that depended on patient age and embryo quality. Ultimately, the goal was Single Embryo Transfer (SET), the transfer of one high quality embryo to eliminate the additional risks associated with multiple pregnancies.

The challenge has been that, despite the transfer of an embryo that appeared of highest quality, one could not tell by simply looking under the microscope that the embryo was genetically normal. Abnormal embryos were not just less likely to implant, but if they did, would miscarry or result in an abnormal fetus.

Technology to test embryos with CCS to determine if they were chromosomally normal before transferring them into the uterus has been available for over 10 years but previously the test was often inconclusive, occasionally inaccurate, and potentially hazardous to the embryos. In addition, the test cost between $5000 and $7000. Today, CCS (also known as PGS) has improved to the point that it is nearly 100% accurate and rarely inconclusive or damaging to embryos and the cost is generally not significantly more than $3000, depending on the number of embryos tested.

Incorporating CCS/PGS into IVF will increase the ability for a patient to achieve a live birth of a normal healthy baby while minimizing the risk for a miscarriage and to do so in fewer embryo transfers since only normal healthy embryos need be transferred. It is envisioned that the additional cost of PGS will be offset by virtue of going through fewer frozen embryo transfers .

These 30 years, I have seen a number of game changers in IVF.  CCS/PGS may be among the most significant.

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Would you consider using CCS/PGD?

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ASRM 2015: Looking Back and Moving Ahead “We Could Always Do More and Do Better”

By David Kreiner MD

October 18th, 2015 at 12:58 pm

It was fitting that this year’s national infertility meeting, the ASRM was held in Baltimore, the city where the recently deceased Dr. Howard W. Jones Jr. first trained and rose to prominence in the field of reproductive medicine.  In the 1950′s and during his career at Johns Hopkins, he was involved in the controversial biopsy of cervical cancer patient, Henrietta Lacks, which led to the most widely utilized and researched cell line of all time.  Thereafter, he became an expert in genetic disorders and reproductive developmental issues that led to his opening the first transgender surgery clinic.  Remarkably, however, “Dr. Howard” (as we students called him) is best known for work he performed after his retirement from Hopkins when he moved to Norfolk and started the first IVF clinic in the Western Hemisphere resulting in the birth of the country’s first IVF baby, Elizabeth Carr, in 1981.

 

My first ASRM (called the American Fertility Society at the time) meeting in 1983 was a showcase of this brand new technology of IVF despite a success of 10% in the best clinics. Reproductive surgery was still more successful than IVF so there were presentations by the premier microsurgeons, laparoscopists and hysteroscopists who were demonstrating the latest advances that were becoming available as instrumentation had improved and laser had become a tool of the reproductive surgeon.  IVF was performed laparoscopically and ovarian stimulations were being performed with some variation of human menopausal gonadotropin, Pergonol, derived from the urine of menopausal women and Clomid.

 

In 2015, we reviewed the impact of social media in the opening presidential lecture urging members of the Reproductive Science community to spread the word about reproductive technology advances and utilize social media tools to educate the public.

 

In this meeting, it was now recognized that the LGBT community needed to become a special interest group within the ASRM with focus on alternative family-building that was available not just to lesbian couples but to gay male couples and transgenders.

 

With the successful fertilization and subsequent pregnancies achieved through egg freezing, fertility preservation for women undergoing cancer treatment, gender reassignment or aging prior to a time when they are ready for motherhood is now available. The technology of egg freezing thrusts upon women important new options to be considered (often on an urgent basis) when preparing for chemotherapy, radiation, hormone therapy or surgery… or simply before aging does irreversible damage to one’s fertility.

 

There was an Acupuncture symposium that presented research demonstrating improved success with IVF when utilized twice a week for at least 4-5 weeks prior to retrieval, before and after transfer.  The use of the mild male hormone, DHEA, was discussed in yet another symposium as a potential benefit to patients with diminished ovarian reserve to optimize number of eggs and embryos and improve pregnancy rates.

 

Elective freezing of embryos to transfer in a non-stimulated cycle and embryo-banking combined with complete genomic sequencing of the embryos to selectively transfer only healthy embryos has demonstrated improved success of IVF. And aside from the increased cost and time involved, it appears to be the ideal approach to IVF today.

 

I think Dr. Howard would be happy with these developments in the field and the direction the society is going both towards a more efficient and safer treatment and to widening its scope to be inclusive of the LGBT community.  Though typical of Dr. Howard, he always thought we could do more and better.  Weeks before his death, he called my friend and former fellow, “Richard S”.  He complemented him on his great work but complained to Richard that he wasn’t measuring some hormone or factor that Dr. Howard thought needed to be checked in Richard’s research…

We have come a long way in the 32 years that I have been active in ASRM. I’m proud that Long Island IVF has always been on the cutting edge of reproductive medical technology with programs and practices already existing for this year’s most popular ASRM topics, including social media, LGBT-focused and friendly alternative family-building, egg-freezing, complete genomic sequencing aka PGS (pre-embryo genetic screening), and acupuncture. Let it never be said that the work is done and that we are satisfied with the status quo.  As Dr. Howard would say, “we could always do more and do better”.

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Have you considered using any of these latest technologies or programs in your family-building plans?

 

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The Fertility Awareness Opportunities Angelina Jolie Missed

By Tracey Minella

March 27th, 2015 at 11:57 am

 

 

credit: Paul Sherman/ wpclipart


Actress, director, humanitarian, ambassador, mom of twins, adoptive mom, wife of Brad Pitt. And she’s gorgeous.

What’s not to hate?

Oh, I’m just sort of  kidding. No, really. But despite all the good she does, there will always be haters. People who want her money, her talent, her babies, or her man. Jealousy can do that.

I don’t necessarily admire many celebrities… and that’s fine, because their only job is to entertain me, not impress me. But I am impressed with Angelina Jolie. She’s charitable with her time and money and seems pretty grounded for a megastar. And she uses her celebrity for good.

It’s been only two years since Jolie made headlines for undergoing a preventative double mastectomy after testing positive for the BRCA gene mutation… a mutation that significantly increases the lifetime risk of getting breast cancer. At that time, she was open about her decision and used her celebrity to increase breast cancer awareness.

Now Angelina revealed that she took those preventative measures to the next level. This time, she had both of her ovaries and fallopian tubes removed in the hope of avoiding ovarian cancer…another deadly cancer linked to the same gene mutation. Jolie lost her mom to ovarian cancer and said in a recent New York Times Op Ed piece that she doesn’t want her children to experience the same loss. Her openness is raising awareness of ovarian cancer.

But there is another untold story here, too…a fertility awareness story…and it needs to be heard.

Unless you’ve been hiding under a rock, you know Jolie has six children. She adopted three children internationally and gave birth to a singleton and a pair of twins. Practically eliminating her risk of getting ovarian cancer is not the only result of her surgery.

The media is reporting that she can no longer have biological children. And Jolie acknowledged how hard her decision would be for a woman who has not completed her family-building. Perhaps because of the size of her family, this point seemed lost on the general public. But it’s not lost on you, is it? This surgery is a big deal. And before others who may not be done with their family-building journeys emulate Jolie and follow her path, some crucial missing information needs to be shared.

In fact, there are three opportunities here to increase fertility awareness and educate the public about advances in the field of reproductive technologies, namely PGD, Egg donation, and Egg-freezing.

First, there’s pre-implantation genetic diagnosis (“PGD”). PGD enables couples who are concerned about passing a life-threatening genetic disease on to their children to have their embryos pre-screened for gene mutations. This screening can only be done in conjunction with an in-vitro fertilization (IVF) procedure, where eggs are retrieved and fertilized in a lab and the resulting embryos can be tested. Then, only those embryos that did not test positive for the mutated gene would be transferred into the uterus…virtually eliminating the chance of passing on that hereditary disease. BRCA is one of the many genes that can be screened through PGD. Long Island IVF offers PGD.

Second, there’s egg donation. If a woman has her ovaries and tubes removed, she cannot thereafter have a biological child…one created using her own eggs… however she may still experience childbirth. If she still has a healthy uterus, it may be possible for her, through IVF, to use eggs from an egg donor and the sperm of her partner or a donor, and have the resulting embryos transferred into her uterus where a pregnancy can implant and grow to term. Long Island IVF’s Donor Egg Program brought Long Island its First donor egg baby decades ago.

Finally, there’s the latest breakthrough in women’s fertility preservation technology: egg freezing. Egg-freezing offers an exception to the egg donor statement above. If… prior to removing her ovaries… a woman undergoes IVF for the purpose of either freezing her retrieved eggs (or freezing the embryos resulting from the fertilization of her retrieved eggs), then instead of needing donor eggs, she would be able to later have her own frozen eggs (or embryos) thawed and transferred into her uterus in the hope of becoming pregnant with her own biological child. Or if her uterus was unsuitable or absent, she could still have a biological child by having someone else carry a pregnancy for her. (Note: Surrogacy and gestational carrier laws vary from state to state.) Long Island IVF has an Egg Freezing Program.

These three fertility awareness opportunities, when coupled with Jolie’s breast cancer and ovarian cancer awareness, will further empower women everywhere to make better medical choices and take charge of their fertility and general health.

Shame on the haters. It’s wonderful that Jolie is open about her health in a way that raises awareness for others. She is a just a mom. A selfless mom who just wants to be there to see her children and future grandchildren grow up.

Is there something wrong with being proactive after tests show you carry a gene that could one day take your life, like it took your mother’s? Are the haters just jealous of her? Is she a hero?

* ** * * * ******** *** * **

What do you think? What would you do?

 

 

no comments

The ABCs of IVF

By David Kreiner MD

May 9th, 2014 at 9:15 am

 

credit: digitalart/freedigitalphotos.net

If you’re not pregnant yet and you’re wondering what to do, this post may shed some light on infertility diagnoses and treatments. Yes, there’s a lot to learn. Yes, it can be overwhelming. But the good news is that you can go to the head of the class by the time you finish reading this post.

Dr. David Kreiner of Long Island IVF gives you the low-down and the lingo. It’s everything you need to know, from A to… well… P. And what better letter to stop at? “P” is for pregnant:

“Why me? My wife never had any infections, surgery or any other problem? I have no difficulty ejaculating and there’s plenty to work with so why can my friends and neighbors and coworkers get pregnant and we can’t?”

I hear these questions daily and understand the frustrations, anger and stress felt by my patients expressing these feelings through such questions. There are many reasons why couples do not conceive. An infertility workup will identify some of these. A semen analysis will pick up a male factor in 50-60% of cases. A hysterosalpingogram will locate tubal disease in about 20% of cases. Another 20-30% of women do not ovulate or ovulate dysfunctionally. A post coital test may identify that the problem is that the sperm is not reaching the egg. It may not be able to swim up the cervical canal into the womb and up the tubes where it should normally find an egg to fertilize. When these tests are normal a laparoscopy may be performed to identify the 20-25% of infertile women with endometriosis. However, even when this is normal and there is no test that logically explains the lack of success in achieving a pregnancy; an IVF procedure may both identify the cause and treat it successfully.

What is IVF?

In Vitro Fertilization, IVF, is the process of fertilizing a woman’s eggs outside the body in a Petri dish. Typically, a woman’s ovaries are stimulated to superovulate multiple eggs with gonadotropin hormones, the same hormones that normally make a woman ovulate every month. Injections of these hormones are usually performed by either the husband or wife subcutaneously in the skin of the lower belly with a very tiny needle. It takes 9-14 days for the eggs to mature. She will then take an HCG injection which triggers the final stage of maturation 35-36 hours prior to the egg retrieval. This is performed in an operating room, usually with some anesthetic. The eggs are inseminated in the lab and 3-5 days later, embryos are transferred into the uterus with a catheter placed transvaginally through the cervix into the womb.

What is ICSI?

Some times even in the presence of a normal semen analysis, and normal results on all the infertility tests, fertilization may not occur without microsurgically injecting the sperm directly into the egg. This procedure is called Intracytoplasmic Sperm Injection or ICSI and may achieve fertilization in almost all circumstances where there is otherwise a sperm cause for lack of fertilization.

If it looks like a sperm and swims like a sperm, why doesn’t it work like a sperm?

A South African gynecologist, Thinus Kruger, discovered that small differences in the appearance of sperm affected the sperm’s ability to fertilize an egg. In 1987, Thinus demonstrated that when we used the very strict Kruger criteria for identifying a normal sperm, we were able to identify most men who had normal semen analyses and were yet unable to fertilize their wife’s eggs. Most of these couples suffered from unexplained infertility except now utilizing the Kruger criteria for sperm morphology we were able to identify the problem. Today, these couples are successfully treated with the ICSI procedure.

Old eggs?

As women age, the percentage of genetically abnormal eggs increases. These older eggs are less likely to fertilize, divide normally into healthy embryos or result in a pregnancy. When older women do conceive they are more likely to miscarry then when they were younger. Aging of eggs begins in the 20’s but accelerates after age 35. This is why a woman’s fertility drops as she gets older. The age at which it becomes significant for a woman varies. Some women in their 30’s have significant aging of their egg. Others less so and may have a good number of healthy eggs into their 40’s.

ABC’s of IVF

Assisted Hatching is when the embryologist makes a hole in the shell around the embryo called the zona pellucidum. This is performed minutes prior to embryo transfer and may be performed chemically with acid tyrodes, mechanically with a micropipette or with a laser. It is commonly believed that older eggs may lead to embryos with a thicker or harder shell that may prevent the natural hatching of an embryo that must occur prior to the embryo implanting into a woman’s lining of her womb.

Blastocyt embryo transfers occur on day 5 or 6 after the egg retrieval. This is the embryonic stage when an embryo normally implants into the womb. These embryos have been selected to be healthier by virtue of the fact that they have made it to this stage. Statistically, the pregnancy rates for women who have had blastocysts transferred is higher than when the same number is transferred on day 3 using “cleaved” embryos of 4-10 cells. As the advantage of the blastocyst transfer may be only a matter of selection, it is thought that there may be no advantage if the embryologist is able to select just as well the best embryos to transfer on day 3 which is typically the case when there are not excess numbers of high quality embryos which will vary according to the patient and be dependent on the age of the patient.

Bravelle – Brand of FSH, follicle stimulating hormone which is a gonadotropin used to stimulate a woman’s ovaries to superovulate and make multiple eggs mature during the IVF cycle.

Cetrotide – Brand of Gonadotropin Releasing Hormone Antagonist that prevents a woman’s pituitary gland from producing LH, luteinizing hormone. LH increases can trigger premature ovulation and stimulate testosterone and progesterone production which can be harmful to a woman’s egg production and prematurely mature the lining of womb potentially affecting implantation.

Co-culture of a woman’s endometrial cells from the uterine lining or granulosa cells from aspirated ovarian follicles along with the embryos in the same culture dish is thought to provide growth factors for the embryos which may improve the health and growth of the embryos.

Cleavage Stage Embryos are 2-10 cell embryos transferred on day 2 or 3. They are often graded by their lack of fragmentation and granularity of the inside of the cell cytoplasm; A to D or 1to 5 with A or 1 being the best grade.

Cryopreservation or freezing can be performed on individual eggs where it may serve as a way to preserve a woman’s fertility either due to aging or in preparation for surgery, chemotherapy or radiation which may affect future access to a woman’s eggs.  It may be performed on cleaved embryos or blastocyst embryos that are already fertilized either because they are in excess of the desired number of embryos to be transferred fresh or to bank for a future PGS/PGD or to improve implantation by delaying transfer to a subsequent unstimulated cycle.

Embryo Glue is a protein supplement to the transfer media prepared minutes prior to transfer to make the embryo more likely to stick to the lining of the womb. It is believed that some embryos may not implant since they are not adhering to the lining and do not get an opportunity to burrow into the endometrium.

Estradiol is produced by the granulosa cells of the follicle which surround the egg in the ovary. As follicles are stimulated and grow they produce more estradiol. We measure estradiol to monitor development of the follicles. It also helps to prepare the lining of the womb for implantation.

Follistim – Brand of FSH, follicle stimulating hormone which is a gonadotropin used to stimulate a woman’s ovaries to superovulate and make multiple eggs mature during the IVF cycle.

Ganirelix – Brand of Gonadotropin Releasing Hormone Antagonist that prevents a woman’s pituitary gland from producing LH, luteinizing hormone. LH increases can trigger premature ovulation and stimulate testosterone and progesterone production which can be harmful to a woman’s egg production and prematurely mature the lining of womb potentially affecting implantation

Gonal F – Brand of FSH, follicle stimulating hormone which is a gonadotropin used to stimulate a woman’s ovaries to superovulate and make multiple eggs mature during the IVF cycle.

Gonadotropins – FSH, follicle stimulating hormone and LH, luteinizing hormone stimulate the follicles in the ovary to mature and produce ovarian hormones, estradiol, testosterone and progesterone. It also is used to stimulate a woman’s ovaries to superovulate and make multiple eggs mature during the IVF cycle. We adjust the ratio of FSH and LH to achieve goals of optimal follicular development and maturation while trying to minimize the risk of hyperstimulation. Typically we administer the gonadotropins to the woman for 8-14 days before giving her HCG 35-36 hours prior to the egg retrieval

HCG is human chorionic gonadotropin, the pregnancy hormone we measure to see if your wife is pregnant. We follow the numbers to monitor the growth and health of the pregnancy. HCG has the same biological effect as LH and therefore can be used to mature the egg in the same way as if it were getting ready to ovulate. We therefore administer HCG to women 35-36 hours prior to the egg retrieval. Brand names for HCG include Pregnyl and Ovidrel.  HCG is occasionally used in place of HMG (Menopur, see below) with similar effects.

HMG – Human Menopausal Gonadotropins are purified from the urine of menopausal women since they have high levels of FSH and LH. Menopur is the brand of HMG used in IVF stimulations containing a 1:1 ratio of FSH to LH. We adjust the ratio of FSH and LH to achieve goals of optimal follicular development and maturation while trying to minimize the risk of hyperstimulation. Adding pure FSH, i.e. Bravelle, Follistim or Gonal F will increase the ratio of FSH to LH which may be desirable especially early in a stimulation. Some patients may not need any supplemental LH and are stimulated with FSH only. HMG is sometimes added towards the end of a stimulation to minimize the risk of hyperstimulation syndrome.

Hyperstimulation syndrome is a condition which occurs approximately 3% of the time as a result of superovulation of a woman’s ovaries with gonadotropins. A woman’s ovaries become enlarged and cystic, fluid accumulates in her belly, and occasionally around her lungs. When it becomes excessive, it may make it uncomfortable to breathe. We remove this excess fluid with a needle. Women can also become dehydrated and put them at risk of developing blood clots. We therefore recommend fluids high in salt content like V 8 and Campbell’s chicken soup. We give patients baby aspirin to prevent clot formation and a medication called cabergoline which helps prevent the development of Hyperstimulation.  It may also be recommended to freeze all the embryos and postpone the transfer to a later cycle as pregnancy can significantly exacerbate Hyperstimulation syndrome as well as potentially be more likely to implant in a subsequent cycle.

ICSI – Some times even in the presence of a normal semen analysis, and normal results on all the infertility tests, fertilization may not occur without microsurgically injecting the sperm directly into the egg. This procedure is called Intracytoplasmic Sperm Injection or ICSI and may achieve fertilization in almost all circumstances where there is otherwise a sperm cause for lack of fertilization

Lupron is a Gonadotropin Releasing Hormone Agonist that must be administered after a woman ovulates or concurrent with progesterone or oral contraceptive pills to effectively suppress gonadotropins. Lupron prevents a woman’s pituitary gland from producing LH, luteinizing hormone. LH increases can trigger premature ovulation and stimulate testosterone and progesterone production which can be harmful to a woman’s egg production and prematurely mature the lining of womb potentially affecting implantation

Monitoring of a woman’s stimulation with gonadotropins is performed by transvaginal ultrasound examination of her ovarian follicles and blood hormone levels. The gonadotropin doses can be adjusted according to the results of the monitoring. The timing of the HCG and subsequent egg retrieval are likewise based on the monitoring. Typically, a woman need not be monitored more frequent than every 3 days initially but may need daily monitoring as she approaches follicular maturation to determine timing of the HCG injection and retrieval.

Morula is the stage between the cleavage stage embryo and blastocyst. It is when the embryo is a ball of cells and is usually achieved by the 4th day after insemination.

Oral contraceptive pills are often given prior to the stimulation to help time stimulation starts and bring a woman’s reproductive system to a baseline state from which the stimulation may be initiated.

PGD/PGS is preembryo genetic diagnosis and screening.  PGD refers to diagnosing the presence of a single gene disorder in the embryo.  Typically, patients with a prior history of producing a child with this disorder or where both partners are known carriers for a genetic disease are candidates for PGD.  Alternatively, patients could make the diagnosis in pregnancy by chorionic villus sampling or amnioscentesis.  PGS is screening for chromosomal abnormalities and has been used to improve success after embryo banking, to prevent chromosomally caused recurrent miscarriages, to improve success with older patients’ IVF cycles and for family balancing/gender selection.  Embryos are biopsied 3 days after retrieval in the cleaved state or 5 or 6 days after retrieval in the blastocyst state. 

Progesterone is an ovarian hormone that prepares the lining of the womb for implantation. We measure it during stimulation to check if the lining is getting prematurely stimulated. We add it to the woman after the retrieval to better prepare the lining and continue it as needed to help sustain the implanted embryo until the placenta takes over production of its own progesterone.  It may be administered as an intramuscular injection in which it is placed in various oil media to facilitate absorption.  It may also be administered as vaginal suppositories or tablets either as compounded micronized progesterone or in the commercially prepared brands; Endometrin and Crinone.

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ASRM Retrospective 30 Years Later

By David Kreiner MD

October 17th, 2013 at 1:48 pm

image courtesy of renjith krishnan/freedigital photos.net

 

Flying into Boston this week it occurred to me that this was the 30 year anniversary of the first ASRM meeting I ever attended.  In 1983, the American Fertility Society “AFS” meeting (as it was called then) was held in San Francisco and I attended as a third year ob-gyn resident. I was in awe attending this huge conference of about 3-5,000 held at the Hyatt Hotel as I recall.


Though I was required to man the Ovcon 35 birth control pill exhibit (since Ovcon’s manufacturer was paying my way), I was drawn to the microsurgery and in vitro fertilization exhibits and presentations.  

In the ballroom, the presenters presided over a few thousand of us eager to hear about the most recent successes in IVF.  Already, Norfolk had achieved dozens of births through this new scientific process which brought gynecological surgeons (laparoscopists) together with embryo biologists, endocrinologists, andrologists and numerous nurses, technicians and office staff.  For me, hearing Dr. Howard Jones, American IVF pioneer, and others speak about their experiences with this life creating technique was exhilarating.

Years later, as a Jones Institute reproductive endocrinology fellow, I would hear Dr. Howard proclaim that a chain is only as strong as its weakest link.  IVF required every link to maintain its integrity for the process to work.

In 1985, I presented my own paper at the AFS meeting in Phoenix, Arizona.  My wife and two sons joined me.  My presentation on endometrial immunofluorescence in front of hundreds of experts and specialists in the field remains one of the strongest memories in my life.

Today, the ASRM must be held in mega convention centers like the one in Boston where it could accommodate tens of thousands of attendees.  One presentation estimated the number of IVF births worldwide at over five million. Interestingly, per capita, the US performs one fifth the number of IVFs as Europe–where IVF is much more accessible and typically covered by government insurance.

Today, success in the US is better than fifty per cent for most people, thereby making single embryo transfer (“SET”) for good prognosis patients a viable option to avoid the risk of multiple pregnancy. Minimal stimulation IVF (“Micro-IVF”) is a viable alternative for many patients, offering a lower cost and lower risk option.  Egg freezing offers a means of fertility preservation, especially valuable to women anticipating cancer therapy.  Pre-embryo genetic screening (“PGS”) is an option that allows patients to screen for and eliminate genetically undesirable embryos that may otherwise lead to miscarriage or termination.

Looking back at the past thirty years, I am amazed at the progress and achievements made by my colleagues in IVF and happy that I was able to participate in this most rewarding field that has brought so much joy to millions of people.

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photo credit: renjith krishnan http://www.freedigitalphotos.net/images/agree-terms.php?id=10058384

 

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The Powerful Impact of PGD in Infertility Treatment

By Tracey Minella

June 13th, 2013 at 11:37 am

credit: Dream designs/freedigitalphotos.net

Preimplantation genetic diagnosis (or screening)…a/k/a PGD or PGS… is a process by which embryos created through in-vitro fertilization (IVF) are screened for various reasons prior to transferring them back into a woman’s uterus in the hope of implantation.
Why would a couple do this?
Well, most people think of infertility as being unable to get pregnant. While that is true, it is only one half of the definition. When you can conceive on your own but can’t maintain the pregnancy, as in the case of recurrent miscarriages, you are also considered clinically infertile.
PGD/PGS can help infertile couples in many ways:
• Improve IVF success rates by selecting for “chromosomally normal” embryos;
• Reduce the incidence of miscarriage;
• Reduce the risk of a live born child with a chromosome or genetic abnormality;
• Reduce cycle numbers to a live birth.

 

Simply put, screening embryos before transfer increases the chance of transferring embryos that are the most likely to implant. Screening may reduce miscarriage or a pregnancy at risk of a baby with a genetic condition.
PGD/PGS can be used to screen embryos for hereditary genetic diseases or conditions and gives couples the choice of transferring back only embryos that do not appear to carry the disease. For example, Spinal Muscular Atrophy (SMA) is a devastating, often fatal disease and is the leading genetic cause of death in infants. The carrier rate for someone to have the gene for SMA is only 1 in 50. Unfortunately, testing for such diseases is not performed prenatally so parents only learn they are carriers after they have a child affected. Other more commonly-known diseases that can be screened by PGD/PGS include Cystic Fibrosis, Tay Sachs, Muscular Dystrophy, and Huntington’s disease. In fact, there are literally hundreds of diseases we can test for with this technology.
PGD/PGS can also screen embryos for chromosomal abnormalities which may be the cause of recurrent miscarriages, enabling the couple to transfer back only viable, chromosomally-accurate embryos. It also can help in cases of repeated implantation failure.
In addition, PGD/PGS can be used for gender selection…choosing the sex of your baby. There are genetic diseases that run through offspring of only one sex, so by selecting to transfer only embryos of the opposite sex, couples can increase the odds of avoiding that disease in their children. However, gender selection can also be used for “family-balancing”, a sometimes controversial topic. Critics cite religious and moral objections to using PGD/PGS for the sole purpose of balancing out your family by choosing embryos of the sex opposite the child(ren) you already have.

 

It may be upsetting to infertile people who need IVF… and would be happy to have it produce a child of any sex… to hear that PGD/PGS can be used for gender selection by those who do not need IVF otherwise. However, others argue that anyone who undergoes the inconvenience and expense of IVF should be entitled to access any and all of the diagnostic tools available through today’s rapidly-developing assisted reproductive technology, including PGD/PGS for any purpose.
It is interesting to note that, although PGD/PGS is an additional out-of-pocket cost over and above traditional IVF, PGD/PGS may lower the overall total cost of IVF for those who produce an excess number of embryos. Since PGD/PGS seeks to select “chromosomally normal” embryos, patients can potentially avoid wasting money on thaw cycles for embryos that would likely not have the potential to develop into viable babies.
Long Island IVF is one of only five infertility practices in the country selected to participate in a recent PGD/PGS study by Reprogenetics. For more information on the study, including whether additional participants can be accommodated, please ask your Long Island IVF doctor, or contact Eva Schenkman, Senior Embryologist at evas@longislandivf.com
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How do you feel about PGD/PGS? Is it acceptable in any case, certain cases, or not at all?

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Exciting Long Island IVF Study Seeks to Prove that PGD/PGS Improves Pregnancy Rates in Older Women

By Eva Schenkman, M.S., C.L.T., T.S.

November 26th, 2012 at 12:49 pm

credit: Dream designs/freedigitalphotos.net

With advancing maternal age more embryos have chromosome abnormalities, from 60% in women younger than 35 to 80% in women 40 and older. This results in embryos failing to implant, pregnancy loss (miscarriage), or affected babies (i.e. Down’s syndrome). Because of that, more than one embryo is usually transferred during IVF. However, if two or more normal embryos implant, twins or triplets may result, which may result in a higher risk of congenital abnormalities, premature birth, and developmental problems.

A technique called PGD/PGS (preimplantation genetic diagnosis/screening) can detect if embryos are normal for chromosomes and may prevent the above problems.

In order to take advantage of this cutting edge technology, a woman must undergo in vitro fertilization (IVF), so her embryos may be examined. Embryos produced after IVF can be tested for the correct number of chromosomes through PGD/PGS.  During this process, a biopsy is performed on embryos on day 3, 5 or 6 of development, by inserting a small needle and withdrawing a few cells. Preliminary studies have shown that the biopsy does not harm the subsequent development of the embryo.

The biopsied cells are sent to a genetics laboratory, Reprogenetics, for rapid PGD/PGS testing using array CGH, a technique that allows for the analysis of all chromosomes, while the embryos remain in the IVF laboratory. PGD results are available in less than 24 hours, and an embryo classified by PGD/PGS as normal, can be transferred back to the woman’s uterus the next day. Extra embryos can be cryopreserved for future attempts at pregnancy.

Most studies performed to date have shown an improvement in pregnancy outcome when PGD/PGS is performed using array CGH.  Yet, so far, only one study (Yang et al. 2012*) has been performed with the utmost scientific rigor, that is, by blindly assigning patients at random to either a control group (no PGD) or to a PGD group.

This study was performed in young patients and showed that PGD significantly improved pregnancy rates even though only one embryo was transferred per woman. However, the same study has not yet been done for older patients (35 and older). In theory, older patients should benefit equally or more than younger ones since they produce more abnormal embryos.

We are excited to report that Long Island IVF has partnered with Reprogenetics and is currently recruiting patients for a study that will determine if this PGD approach is also beneficial for women 35 and older.  

If you are eligible you will be randomly assigned to either a control group (regular IVF and no PGD) or to a PGD group. The cost for PGD will be free. If you are assigned to the control group, have a transfer as a study participant, and do not become pregnant you will be offered PGD for free in your next IVF cycle. Eligibility depends on several factors which are determined at various stages of the IVF process, including the age of the woman (35 or older), having normal ovarian reserve, and producing 3 or more blastocyst embryos by day 5 of development. The PGD group will have only one normal embryo transferred while the control group will have up to two untested embryos transferred.

For more information, including the study’s complete eligibility guidelines and medically-qualifying criteria, contact: Eva Schenkman, MS, CLT, TS Senior Embryologist at Long Island IVF at 631-881-5337 or email at Evas@longislandivf.com  

*[Yang et al, Molecular Cytogenetics. 2012, 5:24] 

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Does the potential of PDG to significantly improve pregnancy rates in older women make this technology something you’d consider using?

Photo Credit: http://www.freedigitalphotos.net/images/Human_body_g281-Dna_p111802.html

 

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