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Archive for the ‘PGS’ tag

4 Hot Fertility Questions at ASRM 2016

By David Kreiner MD

November 7th, 2016 at 7:45 am

The theme for the 2016 ASRM (American Society for Reproductive Medicine) conference in Salt Lake City, Utah was “Scaling New Heights in Fertility”.  As one whose life on Long Island sheltered me from views of snow-capped mountain tops, the perspective of the attendees appeared to climb higher and perhaps to possibilities never previously conceived.

I summarize here 4 Hot Fertility Questions that were debated and discussed in the conference:

1)      Should PGS screening be routine for all IVF patients?

2)      Should all IVF transfers be restricted to blastocysts only?

3)      Should we freeze all embryos and transfer in an unstimulated cycle?

4)      What is the best treatment for the patient with diminished ovarian reserve?

Should PGS screening be routine for all IVF patients? 

The theoretical benefit of Pre-Implantation Genetic Screening, or“PGS”, testing is that it allows one to select a single “tested normal” embryo in the presence of multiple embryos which is more likely to implant and less likely to miscarry.  Absent testing the chromosome number of the embryos, to insure a similar chance of conception one might transfer two embryos– increasing the likelihood that twins would result in a pregnancy at greater risk for prematurity and complications affecting the health of the babies.  Most miscarriages are the result of abnormal chromosomes and if the embryos had normal chromosomes then there should be less of a chance the pregnancy would result in miscarriage.

The argument against routine PGS testing is based mainly on the fact that the test is not 100% accurate or predictive of either normalcy or abnormalcy in addition to not obtaining a result in some cases.  It is argued that the error rate is only 1% but there is a phenomenon called mosaicism where an embryo may have more than one cell line. It is not rare that an embryo which has an abnormal cell line in addition to a normal one can, during development, shed the abnormal cells and evolve normally.  However, PGS testing may pick up only the abnormal cell or detect both normal and abnormal and then there is the question of what to do with the mosaic embryos since there is no current way to predict whether these embryos will ultimately be normal.

Another argument against routine PGS testing is that most abnormal embryos never implant anyway and that perhaps the reduction in miscarriages with PGS is not as great as predicted.  Still another argument that holds true for younger patients in particular is that the pregnancy rate for a single blastocyst transfer is nearly as high without PGS testing and that one can achieve equal success without the risk of discarding potentially normal embryos.

Should all IVF transfers be restricted to blastocysts only?

In addition to improving the ability to select the best embryo, the proposed advantages of a blastocyst transfer (typically 5-6 days old) versus a cleaved embryo transfer (usually 3 days old) include the following:

  • an embryo transferred 5-6 days after ovulation is closer to the natural physiologic state
  • there are thought to be fewer uterine contractions 5-6 days post ovulation than 3 days;
  • blastocysts have a larger diameter and are thought to be less likely to be pushed into the fallopian tubes—which may lead to a lower ectopic pregnancy rate;
  • there is a shorter time to implantation and therefore less opportunity for a deleterious event to occur to an embryo in the uterus.

However, there are some patients, in particular older or those with more fragile embryos, which have been shown to fail to conceive on multiple occasions after a blast transfer but successfully get pregnant and deliver healthy babies after transfer of cleaved embryos.  Furthermore, there is evidence that in some of these cases embryos that may have been destined to otherwise result in a normal pregnancy may fail to develop to blast in the laboratory.

Should we freeze all embryos and transfer in an unstimulated cycle?

There is a growing consensus nationally among IVF programs that the endometrium is less receptive to embryo implantation during a stimulated cycle–especially one in which the estradiol and/or progesterone levels are high.  Although convincing patients to delay transfer to a subsequent unstimulated cycle is a challenge, growing evidence is pushing the field in this direction.

What is the best treatment for the patient with diminished ovarian reserve?

Optimal treatment of the patient with diminished ovarian reserve remains a challenge to the IVF program.  There is growing evidence that adjuvant therapy, including such things as acupuncture and Chinese herbs as well as supplements such as CoQ10 and DHEA, may improve a patient’s response to stimulation and improve pregnancy rates.  Other strategies include sensitizing follicles with estradiol and/or Growth Hormone pre-treatment and banking embryos from multiple cycles with transfer during an unstimulated cycle.  Still another strategy is milder stimulation in an attempt to improve the quality of the retrieved egg/s.

There were many heights achieved during this meeting and to this boy from Queens I was impressed not just with the science and the breathtaking vistas of the regal mountains forming a horseshoe around Salt Lake City but also with the most pleasing goodness of the people native to the city who genuinely offered their time to help make our experience a pleasant one.

 

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The Difference Between Genetic Carrier Screening and Comprehensive Chromosome Screening

By Satu Kuokkanen, MD, PhD

June 6th, 2016 at 12:35 pm

image: cooldesign/ freedigitalphotos.net

Many infertility patients want to know the difference between genetic carrier screening and comprehensive chromosome screening (CCS), as well as why we perform these screening tests.

 

Genetic carrier screening refers to testing of one or both partners for a large scale genetic carrier status of select conditions that often result in severe early childhood diseases in their offspring. Some examples include cystic fibrosis, sickle cell anemia, and spinal muscular atrophy.  It is important to know that these devastating conditions are rare in the general population; however, some of them cluster in certain ethnic backgrounds or geographical regions.

 

Most diseases tested are inherited in recessive fashion, which essentially means that a person will need to have two mutated copies of the gene (one inherited from each parent) to actually get that disease. On the other hand, the carrier status by definition indicates that a person has only one mutated gene of the disease in their genome (DNA) and therefore will never contract the disease, but can pass this mutated gene to their offspring. This situation becomes particularly problematic if both partners are carriers for the same condition because, in such case, each of their offspring will have 1 in 4 or 25% risk of getting that disease. Thus, genetic carrier screening attempts to identify parental carrier status prior to pregnancy to avoid conception with a fetus with severe disease(s).

 

If both parents are carriers for the same genetic condition, the couple can proceed with in vitro fertilization (IVF) in combination with preimplantation genetic diagnosis (often referred as PGD) to essentially weed out affected embryos. Performed on the embryos created after fertilization, PGD tests the embryos for specific gene mutations, prior to transferring any embryos back to the woman’s uterus.  Theoretically, in such scenarios 1 in 4 of the embryos are affected and the rest should be unaffected for the tested condition. The unaffected embryos are transferred to the female partner’s uterus in the hope of establishing a healthy pregnancy.

 

On the other hand, Comprehensive chromosomal screening (CCS), also known as preimplantation genetic screening (PGS) refers to the testing of an embryo’s numeric chromosome component and can be done as part of IVF whether a couple is concerned about genetic diseases or not. Normal female chromosome component is 46, XX and male 46, XY.  Some conditions typically screened for through CCS are Down’s syndrome (extra chromosome 21) and Turner syndrome (missing chromosome X).

 

When CCS is elected, embryos are cultured to day 5, the blastocyst stage, allowing biopsy of a number of cells from each embryo.  The numeric chromosome component of each embryo is then analyzed, thus providing the selection of embryos with normal chromosome numbers for transfer. The improvement in pregnancy rates with CCS makes an elective single embryo transfer a feasible option for many patients, thereby avoiding multiple pregnancies and associated adverse maternal and fetal effects.

 

Importantly, the patients who need genetic carrier screening for specific gene mutations, such as cystic fibrosis, can have their embryos simultaneously analyzed for CCS from the same biopsy.

 

In addition, CCS includes the sex chromosomes: X and Y. When the chromosome screening results of the embryos are available, the information on sex chromosomes becomes optional for patients. Patients can either elect to transfer embryos of a particular gender or may decide not to know the gender of their embryos.

 

As the field of genomics continues to evolve, the ongoing research and clinical trials will provide more information on how and to what extent CCS and other tests can be applied to improve IVF outcomes and establish healthy pregnancies for our patients.

 

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Have you considered genetic carrier screening or comprehensive chromosome screening?

 

 

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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 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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Long Island IVF and the ASRM 2012

By David Kreiner MD

November 5th, 2012 at 10:08 pm

Annually, reproductive endocrinologists and fertility experts from all over the world converge for information sharing and presentations of the most recent scientific advances in our field.  This year, the American Society for Reproductive Medicine (ASRM) meeting took place in San Diego, in a venue that was fertile ground for the growth and development of reproductive medicine.

Among the most exciting topics was the use of pre-implantation genetic screening (PGS) of embryos to improve IVF live birth rates and eliminate miscarriages.  Aneuploidy, the presence of chromosomally abnormal embryos, may be diagnosed through PGS with techniques that can analyze all 23 pairs of chromosomes.  One such method, aCGH (microarray comparative genomic hybridization), is available in most labs on day 3 cleaved biopsies as well as blastocyst biopsies.

The biopsied embryos can be determined to be euploid (chromosomally normal) or aneuploid.  Transfer then can be limited to only the euploid embryos which will eliminate most miscarriages and potentially improve the live birth rate.  This is especially useful in cases of repeat miscarriages and repeat implantation failures.

Whether to have the embryos biopsied on day 3 or day 5 depends on a few factors:

1-         Day 3 biopsy is a somewhat more invasive procedure with a higher rate of mosaicism (embryos containing multiple cell lines) leading to occasional false positive results.

2-         Day 5 biopsies are less likely to lead to fresh transfers.  Success is dependent on the survival of thawed frozen blastocysts.  The recommended form of blastocyst freezing is through vitrification.

Since most miscarriages are the result of implanted aneuploid embryos, we hypothesize that if we add PGS to an IVF protocol we can prevent most miscarriages.

In one study where PGS was performed as an adjunct to IVF/ICSI for patients with recurrent miscarriages (>2miscarriages), it was found that 53.7% of embryos studied were aneuploid in patients with a mean age of 37.5.  In 21.4% of all cases studied all the embryos from the IVF cycle were found to be aneuploid.

I recommend that you ask your physician whether PGS would be useful in your case.

 

 

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How Fertility Issues Might Play Out for William and Kate

By Tracey Minella

May 1st, 2012 at 5:09 pm

 

It’s been one year since the royal wedding and no signs of a baby bump for the new, young Dutchess. Of course, inquiring minds want to know…

My mind is not inquiring. I don’t want to know.  Is yours? I positively loathed all the nagging during my own fertility journey.

Imagine how stressful it must be to be public figures like them, pestered by paparazzi and press who say the worst, hurtful, personal things. And what about the outright lies?

But unlike your average young celebrity couple, poor William and Kate’s royalty status adds a whole other level of stress and spotlight to their life when it comes to the meddling fertility questions. No one with a brain truly cared if J-Lo and Marc, or Mariah and Nick, or any other celebrity couple had children. They could choose not to.

That is not an option exercised by royals. Especially by the future King of England.

Imagine being a royal in line for the throne? Producing an heir is a job requirement! Whether they have a child or not impacts a nation. Which is why there’s such speculation on the subject. That, and the fact that they are an almost universally-loved couple. 

Although I don’t obsess with their family-planning efforts (or lack thereof), I’ve read many blogs speculating on whether Kate was put through any fertility screening prior to the marriage. How awful if that’s the case. If so, it makes me wonder if William was similarly screened. What if  he had issues?

One thing I haven’t seen in these blogs or articles…which struck me right away…was not “What if they do need IVF?”, but rather, “If they do need IVF, would they do sex selection to have a male heir?”

Sex selection, especially when used for gender preference rather than to screen for genetic abnormalities, has been a controversial topic  ever since it became available. Many infertile, childless couples are frustrated or even angered by its use by parents who simply want another child of the opposite sex.

I hope William and Kate (and all couples) will be able to  build their families the natural way when they are ready to do so, and will not be burdened with infertility. Though it would be interesting to see how they’d choose to handle it if IVF ever became necessary. Would they be open about this personal issue and help raise public awareness? Surely they are entitled to the same level of privacy as any couple. Just because you are a celebrity, doesn’t mean you have to make your personal issues public. But imagine what an impact they could have on how the world views infertility if they ended up with fertility issues and chose to go public. (Gee, I hope that didn’t just sound like I wished it on them just so they could champion the cause…I’d never wish infertility on my worst enemy.)

To me the real story, if there is ever one to consider, is in the impact of IVF on the royal world. The basis for the succession of the British monarchy for centuries can now be manipulated and turned on its ear not only by IVF, but by other advances in assisted reproductive technology, like sex selection. Couples who may never have been able to conceive naturally can now not only have a baby, but can take advantage of the heir-producing technology to assure that the throne travels continually down their branch of the family tree. Now you can have an heir with (or without) a spare. 

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What do you think?

 

Photo credit: (public domain): http://fundraisingcoach.com/2011/04/29/3-ways-that-fundraising-is-like-the-royal-wedding/

 

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