Recurrent Miscarriages Need Evaluation

Hello. Last week I received a phone call from a Dear patient that had a tubal reversal not too long ago. It seems that the reversal is working because she has achieved three pregnancies since. Unfortunately, she has miscarried all of them in the first trimester. She lives in a rural area and expressed some frustration that her local physician has not suggested an evaluation for recurrent pregnancy loss. I explained that the most common cause of an early miscarriage is that there has been a chromosomal number problem in the fetuses. These problems increase with age so that someone in her 20s has a risk of miscarriage of about 15% while someone at 40 can miscarry more than 50% of early pregnancies. There is a standard evaluation for patients experiencing miscarriages. The outline of the evaluation is:

1. Anatomic evaluation of the Uterus ( Saline sonogram, HSG, or Hysteroscopy) to rule out fibroids, polyps, and congenital anomalies of the uterus.

2. Blood Chromosome analyses on both partners in order to rule out a chromosomal translocation in the parents. Please review the genetic section of our web site www.geneticsandfertility.com

3. Antiphospholipid antibody tests and Lupus anticoagulant.

4. A general health screen to rule out diabetes, medical problems, or thyroid problems.

5. An endometrial biopsy to rule out chronic inflammation of the womb.

6. Luteal phase progesterone levels.

Despite a thorough evaluation, many patients’ tests do not identify a specific causes. These patients may benefit from IVF with pre-implantation genetic screening of the embryos prior to implantation or reassurance that all that can be tested has been tested.

Best wishes to all.

Dr. Pabon

Julio E. Pabon, M.D. 2014
Julio E. Pabon, M.D. 2014

 

Florida IVF Doctor reviews recent information about In Vitro Fertilization Risks

A recent article published in JAMA (July 2013), Autism and Mental Retardation Among Offspring After In Vitro Fertilization by Sven Saudin et al., reminds us that most well done assessments have shown that the observed problems are most likely the result of the genetics of the patients being treated and not due to the IVF treatment.  Humans have a risk of congenital problems that is in the range of 3-4%.  These congenital problems may be as minor as a mole or as severe as a major heart defect.  The 3-4% risk of congenital anomalies is seen in a fertile population while infertility patients may expect the risk of congenital anomalies to be almost twice that even if a spontaneous conception occurs after prolonged sub-fertility.

As a Florida IVF Doctor, I find this recent report by Saudin et al (JAMA July 2013) very interesting.  He evaluated Swedish infants born between 1982-2007 for the incidence of autism or mental retardation.  They compared the incidence of these conditions in children conceived with IVF as compared to children born after spontaneous conception.  In my opinion, this is the greatest limitation of this study and many others that attempt to see if the IVF procedures are a cause of congenital anomalies or developmental problems.  Studies are flawed because these problems may be inherent to the infertile population or the multiple pregnancy itself and not the IVF procedures.  An example of this type of problem was seen a few years ago when there was a scare about whether IVF procedures were “causing” and increase in the risk of genetic imprinting disorders like the Angelman syndrome.  A follow up study evaluated the incidence of these conditions in the infertile or subfertile population that eventually conceived without IVF found that the conditions had the same incidence in the subfertile population whether they were treated with IVF or not.

Machelle L. Cedars, M.D. is Professor and Director of the UCSF Women’s Health Clinical Research Center.  He wrote an editorial in the same issue of JAMA.  I include some of his comments about this recent report:

“Prior studies have been largely reassuring regarding the risk of autism following IVF. Most of these studies have come from the Scandinavian countries where country-wide databases and registries provide populations for study and linkage with important aspects of both the exposures and outcomes of interest.  However, these studies have been compromised by relatively small sample sizes, poorly characterized outcomes of interest, and limited specific details about IVF and the associated procedures.”

“The results of the study support the absence of an association between any IVF procedure and autistic disorder compared with spontaneous conception.”

Although the authors found a small risk of mental retardation following IVF compared with spontaneous pregnancies (RR, 1.18 [95% CI, 1.01- 1.36]; 46.3 vs 39.8 per 100 000 person-years), this increase became nonsignificant when only evaluating singleton births.”

“The association of multiple birth and preterm birth with these outcomes is particularly important because decreasing the number of multiple births is a primary goal of assisted reproductive technology.”

“The increased risk of autistic disorder and mental retardation, largely accounted for by multiple pregnancies and preterm delivery, should provide another opportunity for reproductive health physicians to educate patients and other physicians about the importance of limiting embryo transfer number.”

“It is somewhat reassuring that the preliminary analyses in the current study failed to show an association with either assessed outcome and day 5 embryo culture.”

“Because ICSI is often used for male-factor infertility and is considered more invasive, it is of particular interest. The study by Sandin et al found an association between ICSI and mental retardation (RR, 1.51 [95% CI, 1.10-2.09]; 93.5 vs 61.8 per 100 000 person-years). However, similar to other outcomes, this relationship became nonsignificant in singletons.”

“The indication for ICSI in many of the studies with identified risk has been severe male-factor infertility. Very low sperm counts and sperm defects are frequently associated with paternal factors including increased genetic risk.”

“A recent study supports the concept that intrinsic genetic abnormalities of sperm may be a source of identified risk with ICSI in cases of very low sperm counts.”

We need to continue to evaluate these issues.  One fact is exceedingly clear.  We need to continue to do our best to avoid multiple pregnancies.  Recent technological advances with more reliable genetic evaluation of the embryos may make a significant difference in reducing the risk of a multiple pregnancy, the most obvious risk factor for potential morbidity.

Julio E. Pabon, M.D., F.A.C.O.G., July 4, 2013IMG_0440

Medical and Laboratory Director

Fertility Center and Applied Genetics of Florida

Sarasota and Bonita Springs, Florida

www.geneticsandfertility.com

 

 

Congratulations to A Riverview/Lakeland IVF Family

Hi Dr. Pabon!  I can’t thank you enough for helping to make our dreams come
true!  It was certainly a challenge, but it was all worth it to finally have
our miracle baby in our arms.  :-)  Caroline is such a sweet, precious baby!
Scott and I are so completely in love!

Amazingly enough, my pregnancy was so easy!  I never had any problems, not
even morning sickness in the beginning.  My doctor closely monitored me to
make sure no problems developed.  I had non-stress tests twice a week
starting at 32 weeks, and had ultrasounds at 32 and 36 weeks to check her
growth.  Luckily though, all was fine and there was never any pre-eclampsia
problems, or any other problems.  Definitely counting my blessings!

Thank you so much for all your hard work to get us to this point.  You truly
are a miracle worker!  I will bring Caroline by sometime soon to meet you
and all your amazing staff.

Thank for your kind words, M.M.

Dr. Pabon and staff

copyright J. Pabon collection
copyright J. Pabon collection

Polycystic Ovarian Syndrome: Updated Ultrasound Criteria

Polycystic ovarian syndrome or PCOS is a very common cause of chronic anovulation and infertility.  Unfortunately, there has been  recent confusion among health care providers as to which patients are most likely PCOS.  The confusion has come from studies that have included patients as PCOS based on ultrasound criteria.

The hallmarks of PCOS are oligomenorrhea (infrequent menstrual cycles due to infrequent ovulation) and hyperandrogenism (the presence of physical manifestations of increased male hormone levels).  Sometimes the history and physical signs can be vague.  For that reason, clinicians and researchers have been looking for more sensitive ultrasound findings.  Unfortunately, the bar for the PCOS criteria for ultrasound findings appears to have been set too low.  This has led to over diagnosing many patients as PCOS.

In my clinic, it is common to see a patient that has been told that she has PCOS based on ultrasound criteria only while she reports regular ovulatory cycles.  This is incorrect.  The findings of this study may lead to less incorrect diagnoses.  The authors report on a higher threshold of 26 or more resting follicles per ovary in patients that also have oligomenorrhea and hyperadrogenism.

The analysis showed that a threshold of 26 follicles struck the best compromise between sensitivity (85%) and specificity (94%) when discriminating between women with PCOS and control participants.

“Using newer ultrasound technology and a reliable grid system approach to count follicles, we concluded that a substantially higher threshold of follicle counts throughout the entire ovary (FNPO)—26 versus 12 follicles—is required to distinguish among women with PCOS and healthy women from the general population.”

Reference:  Hum. Reprod. (2013) 28 (5):1361-1368.doi: 10.1093/humrep/det062First published online: March 15, 2013

Julio E. Pabon, M.D., F.A.C.O.G.

copyright J. Pabon collection
copyright J. Pabon collection

 

IVF Babies not at higher risk of birth defects

Babies born by IVF not at higher risk of birth defects: study

The Associated Press

Published  May 7, 2012

Test-tube babies have higher rates of birth defects, and doctors have long wondered: Is it because of certain fertility treatments or infertility itself? A large new study from Australia suggests both may play a role.

Compared to those conceived naturally, babies that resulted from simple IVF, or in vitro fertilization — mixing eggs and sperm in a lab dish — had no greater risk of birth defects once factors such as the mom’s age and smoking were taken into account.

However, birth defects were more common if treatment included injecting a single sperm into an egg, which is done in many cases these days, especially if male infertility is involved. About 10 per cent of babies born this way had birth defects versus 6 per cent of those conceived naturally, the study found.

PHOTOS

Doctors used a technique called preimplantation genetic diagnosis to screen out embryos that would carry either the BRCA-1 or BRCA-2 gene, linked to breast cancer.

Doctors used a technique called preimplantation genetic diagnosis to screen out embryos that would carry either the BRCA-1 or BRCA-2 gene, linked to breast cancer.

It could be that the extra jostling of egg and sperm does damage. Or that other problems lurk in the genes of sperm so defective they must be forced to fertilize an egg.

“I don’t want to scare people,” because the vast majority of babies are born healthy, said the study’s leader, Michael Davies of the University of Adelaide in Australia.

Couples could use simple IVF without sperm injection, freeze the embryos and implant only one or two at a time, he said. All of those can cut the chance of a birth defect.

The study was published online Saturday by the New England Journal of Medicine and presented at a fertility conference in Barcelona, Spain. Health agencies in Australia paid for the research.

More than 3.7 million babies are born each year through assisted reproduction. Methods include everything from drugs to coax the ovaries to make eggs to artificial insemination and IVF. Fertility treatments account for about 4 per cent of births in Australia and as many as 8 per cent of them in Denmark, where costs are widely covered, Davies said.

In the United States, more than 60,000 babies were born in 2009 from 146,000 IVF attempts. About three-quarters of them used ICSI, or intracytoplasmic sperm injection.

ICSI was developed because of male infertility. But half the time, it was not done for that reason but to improve the odds that at least some embryos will be created from an IVF attempt. Many clinics do it in all cases.

IVF costs around $10,000 to $12,000 per attempt and another $2,000 for sperm injection.

The study used records on nearly 303,000 babies conceived naturally and 6,163 conceived with help in Australia from 1986 through 2002, plus records on birth defects detected by age 5. Researchers counted heart, spinal or urinary tract defects, limb abnormalities and problems such as cleft palate or lip, but not minor defects unless they needed treatment or were disfiguring.

They looked at birth defect rates according to type of fertility treatment. They also had three comparison groups of women who conceived naturally, including some with some history of infertility or who previously needed help to get pregnant.

Among fertility treatments, only ICSI, the sperm injection, resulted in higher rates of birth defects once other factors that affect these odds were taken into account.

“They take a sperm that is probably not normal and force it to conceive,” said Dr. Darine El-Chaar, an OB-GYN at Canada’s University of Ottawa. She led a smaller previous study of this and called the new work impressive and “the study that needed to be done” to sort out the source of these risks.

In the study, frozen embryos were less likely to result in birth defects than fresh ones used soon after they were created. Defective ones may be less likely to survive freezing and thawing, so the fittest embryos result in pregnancies, Davies said.

Babies born to women with a history of infertility who ended up conceiving on their own, or who had natural pregnancies after assisted ones, also had higher rates of birth defects. That suggests that infertility itself is playing a role.

Dr. Glenn Schattman, president of the Society for Assisted Reproductive Technologies and a Cornell University fertility specialist, said it was reassuring that ordinary IVF is safe. If ICSI is chosen because male infertility is involved, “parents have to be aware that by having a child with their own genetic material, they might be increasing their risk” of a birth defect, he said.

Dr. Joe Leigh Simpson, a geneticist and research chief at the March of Dimes, said doctors should take this work seriously and discuss it with patients. He said techniques have improved over the last decade and ICSI may be safer now than when this study began.

Even with genetic testing for various diseases, “we always tell our patients that this doesn’t guarantee a perfect baby,” he said.

Dr. Julio E. Pabon, Medical director of Fertility Center and Applied Genetics of Florida and faculty member of Florida State University College of Medicine, agreed with Dr. Simpson’s comments while adding that congenital anomalies seen when ICSI is used to overcome a very severe male factor problem, there may be genetic aberrations present in the father that increase the risk of urogenital anomalies in the male children because the genetic information for the genes that may have caused the infertility may be closely linked to other developmental genes.  The anomalies are uncommon and are usually easily diagnosed and treated.  “Couples do not choose to use a sperm donor to avoid ICSI.”

Naples IVF Patients Have Access To The Highest Technology

IVF Technology advances with Pre-implantation genetic screening, vitrification, and single embryo transfers.

Twin and higher order pregnancies are considered a complication of IVF and super-ovulation.  Twin and Higher order pregnancies can end prematurely in more than 70% of cases.  Pre-term birth is very dangerous for babies.  There can be respiratory, vascular, intestinal, infectious, and brain complications that can lead to a life of disability.

IVF patients have been asking on a weekly basis for twin pregnancies.  Patients say things such as “twins are cute,” or “I only want to go through one pregnancy,” or “I am older and only want to go through one more pregnancy.”  Some patients also focus on the cost of ART treatments and the desire to increase the chance of a live birth by implanting more embryos.  I assure you that the cost of the NICU and the care that a pre-term baby or babies with short term or long term morbidities may require is many, many, many times higher that the cost of many IVF tries.

Up until recently, we have usually transferred one or two embryos into younger patients early in the process.  Sometimes more embryos are transferred in special situations.

Recently, technology has changed.  One such change has been the new freezing technology called Vitrification.  With this technology, the pregnancy chance with a fresh embryo transfer is similar to that of a frozen/thawed embryo transfer.  Therefore, there is not a “fear” of freezing embryos anymore.  In the past, frozen/thawed embryo transfer pregnancy rates were a fraction of a fresh transfer.  Nowadays, the transfer of a frozen/thawed embryo into a “programmed” uterus may result in a higher chance of pregnancy than the transfer of a fresh embryo into a hyper stimulated patient.  That is why many patients hear the “all freeze” protocol information in our consultations.  The better freezing technologies present patients with the choice of transferring one embryo at the time.

Unfortunately, a single embryo transfer carries a lower chance of pregnancy than when 2 or 3 are transferred.  Most younger patients can expect a chance of pregnancy with a single embryo in the range of 35-40%.   So, commonly, patients will ask for two.

Recently there is a whole new technology that is really a game changer.  Pre implantation genetic screening of embryos at the blastocyst stage yields such good data that patients can expect a chance of pregnancy in excess of 80% per transfer per single embryo.  The reason for this huge jump is that the single embryo being transferred has been shown to carry the normal number of chromosomes by very powerful technology.

With pregnancy rates in excess of 80% per “normal” embryo transferred (normal within the limits of the technology), transferring two such tested embryos is essentially a planned twin pregnancy.

I have been trying to counsel our patients to accept single embryos for transfer, but many are still pushing and pushing.  At this time we can manage cases on a one on one basis, but patients should educate themselves of the risks to themselves and their babies. I have discussed this issue with our Maternal Fetal Medicine consultants and they all support the transfer of single embryos after PGS with trophectoderm blastocyst biopsies and 24 chromosome microarray complete genomic hybridization.

I will follow this post with the American Society of Reproductive Medicine document about multiple pregnancies.

Julio E. Pabon, M.D., F.A.C.O.G.

www.geneticsandfertility.com

copyright J. Pabon collection
copyright J. Pabon collection

CEO Fertility Center and Applied Genetics of Florida

Assistant Clinical Professor/Florida State Univ. College of Medicine

 

 

ASRM Mourns Loss of IVF Pioneer Sir Robert Edwards

ASRM Mourns Loss of IVF Pioneer Sir Robert Edwards
ASRM released the following statement this morning, attributable to Linda C. Giudice, MD, PhD, President, American Society for Reproductive Medicine.
“All of us in the American Society for Reproductive Medicine mourn the passing of Sir Robert Edwards.
Dr. Edwards was a great scientist whose stellar scientific work advanced our understanding of human reproduction, human embryonic stem cells, advanced pre-implantation genetic diagnosis and revolutionized the treatment of infertility. We extend our condolences to his family, and his many friends around the world.”
The Nobel Prize-winning scientist worked with Dr. Patrick Steptoe to bring about the birth in 1978 of the first baby conceived through in vitro fertilization.  See  BBC News coverage- “Test-tube baby pioneer Professor Sir Robert Edwards dies” at http://www.bbc.co.uk/news/uk-england-cambridgeshire-22091873.
images

Is A Planned Twin IVF Pregnancy Wrong?

Twin and higher order pregnancies are considered a complication of IVF and super-ovulation.  Twin and Higher order pregnancies can end prematurely in more than 70% of cases.  Pre-term birth is very dangerous for babies.  There can be respiratory, vascular, intestinal, infectious, and brain complications that can lead to a life of disability.

IVF patients have been asking on a weekly basis for twin pregnancies.  Patients say things such as “twins are cute,” or “I only want to go through one pregnancy,” or “I am older and only want to go through one more pregnancy.”  Some patients also focus on the cost of ART treatments and the desire to increase the chance of a live birth by implanting more embryos.  I assure you that the cost of the NICU and the care that a pre-term baby or babies with short term or long term morbidities may require is many, many, many times higher that the cost of many IVF tries.

Up until recently, we have usually transferred one or two embryos into younger patients early in the process.  Sometimes more embryos are transferred in special situations.

Recently, technologies have changed.  One such change has been the new freezing technology called Vitrification.  With this technology, the pregnancy chance with a fresh embryo transfer is similar to that of a frozen/thawed embryo transfer.  Therefore, there is not a “fear” of freezing embryos anymore.  In the past, frozen/thawed embryo transfer pregnancy rates were a fraction of a fresh transfer.  Nowadays, the transfer of a frozen/thawed embryo into a “programmed” uterus many times has a higher chance of pregnancy than the transfer of a fresh embryo into a hyper stimulated patient.  That is why many patients hear the “all freeze” protocol information in our consultations.  The better freezing technologies present patients with the choice of transferring one embryo at the time.

Unfortunately, a single embryo transfer carries a lower chance of pregnancy than when 2 or 3 are transferred.  Most younger patients can expect a chance of pregnancy with a single embryo in the range of 35-40%.   So, commonly, patients will ask for two.

Recently there is a whole new technology that is really a game changer.  Pre implantation genetic screening of embryos at the blastocyst stage yields such good data that patients can expect a chance of pregnancy in excess of 80% per transfer per single embryo.  The reason for this huge jump is that the single embryo being transferred has been shown to carry the normal number of chromosomes by very powerful technology.

With pregnancy rates in excess of 80% per “normal” embryo transferred (normal within the limits of the technology), then transferring two such tested embryos is essentially a planned twin pregnancy.

I have been trying to counsel our patients to accept single embryos for transfer, but many are still pushing and pushing.  At this time we can manage cases on a one on one basis, but patients should educate themselves of the risks to themselves and their babies. I have discussed this issue with our Maternal Fetal Medicine consultants and they all support the transfer of single embryos after PGS with trophectoderm blastocyst biopsies and 24 chromosome microarray complete genomic hybridization.

I will follow this post with the American Society of Reproductive Medicine document about multiple pregnancies.

Julio E. Pabon, M.D., F.A.C.O.G.

www.geneticsandfertility.com

copyright J. Pabon collection
copyright J. Pabon collection

CEO Fertility Center and Applied Genetics of Florida

Assistant Clinical Professor/Florida State Univ. College of Medicine

 

 

Doctor Pabon Will Attend 2013 London Fertility Show

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Dr. Pabon, C.E.O., Medical and Laboratory Director of Florida’s premier IVF center will attend the London Fertility Show in November 2013.  He and his staff will be at booth 18 during the meeting to answer questions about all aspects of IVF and assisted reproductive techniques and how we help patients from Europe.  Please view our web site at www.geneticsandfertility.com or www.drpabon.com for further information.

A Doctor Pabon baby in London Copyright J. Pabon collection
A Doctor Pabon baby in London
Copyright J. Pabon collection