Florida IVF Specialist and New Endometriosis Guidelines

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As a busy practicing IVF specialist I welcome good summaries of useful information.  Endometriosis is a very common affliction.  It is estimated that 15% of the female population has endometriosis while about a third of patients suffering with infertility may have it.  As the years pass, more good information is emerging that has diminished the indications for surgery for the endometriosis patient that is infertile.  Recently, we have learned that patients may gain little from aggressive removal of ovarian endometriosis because that may significantly reduce their ovarian reserve.  More patients are being treated with IVF instead of surgery.  Of course, this approach does not apply to patients that need improvement of significant symptoms like pelvic pain, incapacitating menstrual pain, or painful intercourse.  Below please find and excellent article written for Medcape by Peter Kovacs, MD, PhD summarizing new guidelines from the European Society of Human Reproduction and Embryology.

ESHRE Guideline: Management of Women With Endometriosis

Dunselman GA, Vermeulen N, Becker C, et al

Hum Reprod. 2014;29:400-412


Endometriosis can be diagnosed when endometrial tissue is found in extrauterine locations. It is found in 10%-15% of the general population and in up to one third of the infertile population.[1] There are various theories that attempt to explain its etiology. Some cases can be explained by retrograde menstruation, but metaplasia, hormonal, inflammatory processes, and abnormal cytokine function also seem to play a role.[2]

A wide variety of symptoms may accompany endometriosis. Some women are asymptomatic, whereas others are affected by dysmenorrhea, menorrhagia, dyspareunia, chronic pelvic pain, and urinary and gastrointestinal symptoms. The symptoms typically recur in a cyclic fashion, and an exacerbation can occur around menstruation.

The diagnosis can be suspected on the basis of symptoms but is established when histologic confirmation of endometrial glands and stroma is made from a tissue biopsy sample obtained from an extrauterine location.

Treatment may involve management of the symptoms, medical therapy to suppress endometriosis, and conservative or definitive surgical therapy. The decision is typically made on the basis of the severity of the symptoms, the age of the patient, her wish for future fertility, and potential contraindications to certain therapies.

The Guideline

This guideline is an update of an earlier one aiming to address all important diagnostic and therapeutic issues related to endometriosis.

The authors discuss that various cyclic symptoms and physical findings may raise the possibility of endometriosis, but the gold standard to establish the diagnosis is histologic analysis of tissue samples obtained at the time of surgery. Ultrasonography, MRI, and certain biomarkers may also raise suspicion but should not be used alone to establish diagnosis.

Empirical treatment of pain (without using surgical confirmation) using analgesics or suppressive therapy with oral contraceptive pills (OCPs) may be appropriate for young patients. Hormonal treatment using OCPs, progestins, androgens, and gonadotropin-releasing hormone (GnRH) agonists are all appropriate to manage pain associated with endometriosis. OCPs, especially if use is extended, are appropriate to manage dysmenorrhea and dyspareunia. GnRH agonists with or without hormonal add-back may also be offered to manage painful symptoms.

Surgery and excision or ablation of endometrial implants is also effective to manage endometriosis-associated cyclic symptoms, and providers are encouraged to proceed with removal of endometriosis at the time of diagnosis (“see and treat”). Ovarian endometriomas should be removed by cystectomy, rather than drainage and coagulation, to avoid recurrence. Deep infiltrating endometriosis should be managed by experienced surgeons, because complication rates are high. There is no proven benefit of hormonal treatment as adjuvant therapy to surgery, but nor is there proven harm with this approach. After cystectomy, hormonal therapy may be offered to reduce the risk for recurrence in patients who do not seek immediate conception.

Dietary supplements, transcutaneous nerve stimulation, traditional Chinese medicine, and acupuncture have not shown to be effective for the management of endometriosis.

Medical therapy alone does not improve one’s chance of achieving a pregnancy and should not be offered for this reason. Surgical treatment of early-stage endometriosis improves fertility outcome. Operative laparoscopy can be considered to manage advanced-stage endometriosis (stage III-IV). Before surgical removal of endometriomas, the ovarian reserve should be assessed and the results should be considered. Hormonal treatment after surgical removal of endometriosis has not been shown to improve fertility outcome.

For the infertile patient with early-stage endometriosis (stage I-II), intrauterine insemination can be offered to improve the chance of pregnancy. Success rates of in vitro fertilization seem to be lower among women with endometriosis, but reports are conflicting. GnRH agonist down-regulation for 3-6 months immediately before IVF may improve treatment outcome. The removal of larger endometriomas (> 3 cm) has not been shown to improve IVF outcome, although surgery is recommended to those with painful symptoms. After surgical removal of endometriomas and before IVF is started, hormonal therapy may be considered to reduce the risk for recurrence.

Postmenopausal women with a history of endometriosis should be offered combined hormonal treatment instead of estrogen alone if hormone replacement is needed.



Endometriosis is a rather common, benign gynecologic disease. It is defined as the presence of endometrial tissue outside the uterine cavity. The diagnosis is established by histologic confirmation of both endometrial glands and stroma in tissue specimens obtained at the time of surgery.

Asymptomatic endometriosis does not require surgical treatment, because the natural course of the disease is not known. Patients with recurrent symptoms that are not responsive to medical treatment and significantly affect everyday quality of life may need to be managed with definitive surgery: removal of the uterus and ovaries. For those with less severe symptoms, a wide variety of therapies can be offered.

Medical therapy may involve the use of nonsteroidal anti-inflammatory drugs when the main problem is the cyclic occurrence of painful symptoms. Hormonal therapy that suppresses endometriosis and induces the regression of endometrial tissue has been shown to improve pain, dysmenorrhea, and dyspareunia. OCPs, progestins, androgens, and GnRH agonists can all be considered for this purpose. Deep infiltrating endometriosis often requires surgical management. The procedure should be done by experienced surgeons, as the risk for bladder and bowel injury is relatively high and it may require the resection of the affected bowel segment.

Endometriosis can be detected in up to one third of infertile women.[3,4] Its impact depends on the stage of the disease. Even early-stage endometriosis may lower implantation rates. Surgical treatment of early-stage disease has been shown to improve pregnancy rates.[5] Advanced-stage endometriosis may distort the anatomy and could result in infertility. Surgical correction can be considered, but most of these patients will eventually require IVF. Suppression of endometriosis with a GnRH agonist or extended OCP use improves IVF outcome.

The management of ovarian cysts may pose a clinical dilemma. One the one hand, cysts may lower the response to stimulation, could interfere with successful oocyte collecting during IVF, and may be associated with pain. They may also increase the risk for adnexal torsion during pregnancy when left untreated. On the other hand, even the most careful surgery could negatively affect ovarian reserve when healthy tissue is removed as well. A patient with already compromised ovarian function is likely not to benefit from the surgery. For those without associated symptoms, the removal of endometriomas is not required. Patients with symptoms associated with endometriosis, however, most likely would benefit from surgery before fertility treatment.[6]

Endometriosis is associated with a wide variety of symptoms, and treatment is needed in symptomatic patients. Treatment may involve surgery, medical therapy, or a combination of the two. The treatment has to be individualized to address the patient’s symptoms and her desire for fertility. Treatment should also be determined by assessing the risk/benefit ratios of the various hormonal surgical options.


  1. Somigliana E, Infantino M, Benedetti F, Arnoldi M, Calanna G, Ragni G. The presence of ovarian endometriomas is associated with a reduced responsiveness to gonadotropins. Fertil Steril. 2006;86:192-196. Abstract
  2. Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39:535-549. Abstract
  3. Barnhart K, Dunsmoor-Su R, Coutifaris C. Effect of endometriosis on in vitro fertilization. Fertil Steril. 2002;77:1148-1155. Abstract
  4. Harb HM, Gallos ID, Chu J, Harb M, Coomarasamy A. The effect of endometriosis on in vitro fertilisation outcome: a systematic review and meta-analysis. BJOG. 2013;120:1308-1320. Abstract
  5. Marcoux S, Maheux R, Bérubé S. Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis. N Engl J Med. 1997;337:217-222. Abstract
  6. Garcia-Velasco JA, Somigliana E. Management of endometriomas in women requiring IVF: to touch or not to touch. Hum Reprod. 2009;24:496-501. Abstract

Fox News Medical “A” team incendiary statements about PGD

I am a frequent watcher of Fox and Friends in the morning.  I have enjoyed their show as well as the medical “A” team.  The medical “A” team has always been quite objective and interesting.

I was surprised on Feb 20th, 2014, when I saw and heard Dr. Marc Siegel comment on new PGD technology that allows us to test embryos for the presence of the BRCA Breast Cancer Mutations.  The usually objective Dr. Seigel  seemed to be fine with the test, but then went on to share his anxiety about the potential of PGD to lead us down the pathway of genetic engineering and the possibility that we may create an “evil super race” akin to the evil super beings from “Star Trek.” I was surprised to see Dr. Seigel go down the road of the news correspondent that tries to sensationalize a story for ratings.

Dr Siegel should have emphasized that Pre-implantation Genetic Diagnosis allows physicians like me to treat a family and many subsequent generations.  There are many horrible genetic mutations that lead to severe morbidity and the early death of children.  A mother that has lost a baby in her arms due to one of these conditions like cystic fibrosis or spinal muscular atrophy or a family that has dealt with the severe mental afflictions of Fragile X should have the choice to grow their family with much reduced risk of the known disease that they wish to avoid.  Dr. Seigel did acknowledge the usefulness of PGD in these severe and lethal conditions, but should not criticize families that may choose to modify the risk of a condition like breast cancer in their offspring.  Statements like the ones made on Fox and Friends alluding to physicians like me may potentially create an “evil superhuman race” are incendiary at the least and should not be made by a true man of science.

Twenty seven years ago I chose my career path with the hope that I would be able to apply genetic knowledge for the prevention of human afflictions.  Now it is part of my daily practice.  It is a powerful practice that inspires and humbles at the same time when we choose to implant a human pre-embryo that we know is free of the affliction to which his or her older sibling succumbed.

Julio E. Pabon, M.D. , F.A.C.O.G.IMG_0440 copy


Fertility Center and Applied Genetics of Florida


Tampa / Sarasota Clinic Leads in New IVF Technology

Our Tampa / Sarasota IVF Clinic leads in the application of new PGS / PGD IVF technology in Florida.  Our results from our 2012 IVF with PGS / PGD Blastocyst Laser assisted trophectoderm biopsy program show that patients that had a single euploid (number of chromosomes) embryo implanted had great success.  Patients that had fresh single embryo transfer achieved a pregnancy in 75% of cases.  More than 90% of patients who were treated with “all freeze” protocols followed by single euploid transfers achieved a pregnancy.  These results exclude patients that had abnormal endometrial lining development.nav

New IVF technology has allowed us to increase the probability of a normal pregnancy while limiting serious complication of Assisted Reproductive Technology associated with multiple pregnancies.  Our program has also eliminated severe ovarian hyper-stimulation as a complication due to our lupron trigger protocol and “all freeze” protocols.

Contact us at (941) 787-2287 or at www.geneticsandfertility.com or www.drpabon.com

Dr. Pabon in Sarasota
Dr. Pabon in Sarasota

Do fertility drugs increase the risk of ovarian cancer?

Fertility Drugs like Clomid, Menopur, Pergonal, Gonal F, Follistim, and others have been used for many years to induce ovulation in both women who don’t ovulate and those that need to produce more than one egg at the time.  Physicians have tracked whether patients have a higher risk of future ovarian cancers after receiving such drugs.  So far there is no evidence that shows that there is a higher risk of ovarian cancers after using fertility drugs.  What we know is that actually being pregnant or using a birth control pill can lower the risk of future ovarian cancers.  Here is a recent article that reassures us in this regard.  Note that patients that took Clomid and then never became pregnant did have a higher risk of future ovarian cancer.  This implies that the risk may not have been increased by the drug, but because the patients did not conceive and did not use oral contraceptives either.

Julio E. Pabon, M.D., F.A.C.O.G., October 2013IMG_0440 copy


No Increased Risk of Ovarian Cancer Found With Common Fertility Drugs

October 14, 2013


By Lorraine L. Janeczko

NEW YORK (Reuters Health) Oct 14 – Women taking ovulation-inducing drugs are not at increased risk of ovarian cancer, researchers have found.

Writing in Fertility and Sterility, online September 6, Dr. Britton Trabert and colleagues note that the use of fertility treatment has been on the rise. It is biologically plausible, they add, that ovulation-inducing drugs could be associated with ovarian cancer.

But as Dr. Trabert told Reuters Health by email, “we found no evidence that either clomiphene or gonadotropins, the drugs in our study most commonly used to treat infertility, were associated with an increased risk of ovarian cancer.”

Dr. Trabert, from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute in Bethesda, Maryland, and her colleagues analyzed data from women seen for infertility at five large U.S. practices between 1965 and 1988.

Nearly 10,000 women with at least one intact ovary were included in the study. The researchers followed the cohort for a mean of 17.6 years for ovarian cancer cases (n=85) and for a mean of 26.2 years for non-cases.

Overall, they found no association of ovarian cancer risk with ever use of CC (adjusted relative risk 1.34; 95% confidence interval 0.86 to 2.07) or gonadotropins (aRR 1.00; 95% CI 0.48 to 2.08).

However, women who used CC and remained nulligravid at follow-up were at higher risk of developing ovarian cancer than were those who successfully conceived, compared with nonusers (aRR 3.63; 95% CI 1.36 to 9.72 vs. aRR 0.88; 95% CI 0.47 to 1.63, respectively).

Dr. Trabert said it remains unclear whether nulligravid women on anti-ovulation drugs are at higher risk than are nulligravid women without exposure to the medications.

“These findings shouldn’t influence current treatment practices,” she said. “Our study evaluated drugs as they were prescribed mainly in the 1970s and 1980s, and many of the exposures were much higher than those with the drugs used today.”

Dr. Caren M. Stalburg, who wasn’t involved in the study, said the findings are reassuring and consistent with earlier meta-analyses that showed no link between ovulation-inducing drugs and ovarian cancer.

“They may also help identify a subset of individuals who are at increased risk for ovarian cancer long-term, that is, those women who remain nulligravid after the use of clomiphene citrate,” Dr. Stalburg, an ob-gyn at the University of Michigan Medical School in Ann Arbor, told Reuters Health by email.

“Given that we do not have effective mechanisms for ovarian cancer screening, it is unclear how these individuals should be monitored per se,” she added. “Awareness of the risks in this subset of women may be all that is possible for now.”


How Old is Too Old To Become a Parent?

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This is a difficult question.  As Reproductive Endocrinologists, it seems that the boundaries of acceptability are always changing.  In my practice, we do not discriminate on the basis of age.  Older patients are informed of the increased risk of pregnancy complications such as hypertension, diabetes, and pre-term birth that are more common as patients age.  Patients are treated into their late forties and  and early fifties.  We screen patients very thoroughly and require a cardiac stress test for those over 45.  Patients that choose to try to conceive in their mid forties or later are informed that they have to be in optimal health and not have significant “co-morbidities.”  The most common one of these is obesity.  If a patient wishes to try to become pregnant later in life, she needs to demonstrate  that she is not increasing the risk further by being obese.

I try to educate patients about the ethics of advanced age parenting and assess the family structure to make sure kids will be cared for if the older parents become ill.

There was and interesting case a few years ago in Florida when a lady called a Florida IVF clinic and was turned away by the receptionist “because of her age.”  It turns out the patient was in the legal profession and sued that clinic for age discrimination.

The article below comments about a terrible event in Italy and suggests that there should be legal age limits imposed upon patients and clinics.  Who is to decide what is the proper limit.  What about an older man that marries a younger lady or vice versa.  It is best to make these assessments on an individual basis instead of making more rules.  I hope that U.S. Reproductive Endocrinologists will use good judgement on a case by case basis.

Here is the article as reported in the A.P. by A Vasireddy and S. Bewley

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


How Old Is Too Old to Become a Parent?

Tragic Outcome of Post-menopausal Pregnancy: An Obstetric Commentary

Vasireddy A, Bewley S
Reprod Biomed Online. 2013;27:121-124


Initially, in vitro fertilization (IVF) was offered to overcome the problem of tubal disease. As experience has grown with the treatments and as the technology has improved, IVF has become available to a wider patient population, based on more heterogeneous indications. Nowadays, it is offered to treat male factor, tubal, immunologic, hormonal, unexplained, etc. causes of infertility. Over the years, it also became evident that the treatment can be successfully completed with donated gametes (egg, sperm donation) or when the embryo is implanted into a surrogate’s uterus. This has opened up new areas of use. The availability of such “nonclassic” methods also raises legal and ethical questions.

A trend in delaying childbearing can be observed in the past decades. Women in increasing numbers continue their education and seek a professional career. In modern societies, it also seems more difficult to establish stable relationships that could be the base of a family. The result of these changes is that more and more women start thinking about conceiving once they are already over 30.

The ovaries contain a finite number of eggs. Reduced oocyte availability and poorer egg quality are associated with increased reproductive difficulty as women age. While under 30 years of age, only 5%-10% of couples face infertility problems. By the age of 40, the incidence of infertility is over 40%. Over the age of 45, women rarely conceive on their own or with assisted reproductive technology (ART).

Age-related problems in the woman can usually be overcome with the use of donated oocytes. This commentary article discusses the ethical and biological aspects of oocyte donation at an advanced age in relation to a controversial legal case.

Commentary Summary

According to a 2011 report, an Italian court took a 1-year-old child away from a couple as they were considered too old to be fit parents at the female age of 57 and male age of 70. The child was conceived through ART treatment abroad.

The authors discuss that as women age, the proportion of embryos affected by aneuploidy increases, and this is a major limiting factor in achieving pregnancy in the late 30s and early 40s. The uterus also shows some signs of aging, probably related to suboptimal blood supply, but this seems to be less of an issue because the age factor can be overcome by the use of donated oocytes.

It is also known that pregnancies at the extremes of the reproductive years are associated with a higher frequency of medical complications (hypertensive complications, gestational diabetes, preterm delivery, stillbirth, operative delivery). A pregnancy conceived through egg donation in a woman with advanced age is also associated with an increased incidence of medical complications, so the use of “young” eggs does not prevent these complications.

Even if a pregnancy progresses uneventfully and results in the delivery of a healthy child, one has to consider the chronic medical problems and malignancies that affect women in the fourth through sixth decades of life when they need to raise the child. While one tries to help couples whose last resort is gamete donation, the interest of the offspring also needs to be considered. Should the parents become incapable of fulfilling their parental responsibilities, it will become the responsibility of the society to provide care for these children. Therefore, the authors feel that the fertility treatment of women of advanced age or even in menopause should be regulated to avoid future cases like that in Italy.

Age is probably the single most important parameter affecting reproductive success. A woman’s chance to conceive starts to decline at around the age of 30, and over 45 it is very rare to achieve a successful pregnancy. This is due to the reduced number of eggs available for fertilization as well as to their poorer quality that leads to increased aneuploidy rates with age. Women who delay childbearing can expect a longer time to succeed, more need for ART, and smaller family size. ART may compensate for some of the reduced chance but cannot make up for all of it. Pregnancies that are conceived in women over 35 are complicated by higher miscarriage and stillbirth rates; medical complications during pregnancy are more common too.

Women over 40 are more likely to require donor eggs to achieve a pregnancy when compared with younger women. An embryo that is created from a younger woman’s egg will have a high chance to implant, so women even after reaching natural menopause still have a chance to achieve a successful pregnancy. However, they need to be aware that these pregnancies are still complicated by more hypertensive complications, low birth weight, and need for operative delivery.

A child born to older parents may face relationship or emotional problems with his/her parents due to the big age gap. On the other hand, older parents are more likely to be able to provide the financial needs required to raise a child. The availability of social egg freezing is another issue that will likely result in more pregnancies among women of advanced reproductive age. Freezing eggs at a younger age allows women to study and start a job before they interrupt their professional career with a pregnancy and delivery. These women will probably not have big families that may have consequences to society. These women may also be diagnosed with medical problems or may be affected by undiagnosed medical issues by the time they decide to use their eggs, which may complicate the pregnancies and may lead to a higher rate of maternal morbidity/mortality.

Therefore, care providers have to be very careful when counseling women about pregnancies at an older age. Women should be encouraged to try on their own at a young age. Those who for various reasons cannot complete their desired family size early on should undergo a thorough medical evaluation before their own or donated eggs are used. An upper age limit should also be set to avoid problems like the one discussed in the article and to make sure parents will be there for their children until their children at least reach adulthood.


Fertility Options for Cancer Patients

The Sarasota oncofertility meeting last weekend reviewed fertility options for cancer patients.  The first oncofertiity meeting in Sarasota was successful in elevating awareness of the fertility options for cancer patients.  I give my thanks to Joann Heaton, MS, ARNP, AOCNP, ACHPN, Nurse Educator of Sarasota Memorial Hospital as well as the Medical Education committee of SMH for all the effort and planning of the meeting.  I also give special thanks to Dr. Quinn from Moffitt Cancer Center for her participation.


Scottish Loch Copyright J. Pabon collection
Scottish Loch
Copyright J. Pabon collection

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

Fertility Center and Applied Genetics of Florida

Sarasota and Bonita Springs, Florida  U.S.A.

Here is a recent publication form the American Society of Clinical Oncologists:

Fertility Preservation in Patients with Cancer: American Society of Clinical Oncology Guideline Update

Published online before print May 28, 2013, doi: 10.1200/JCO.2013.49.2678
Alison W. Loren, Pamela B. Mangu, Lindsay Nohr Beck, Lawrence Brennan, Anthony J. Magdalinski, Ann H. Partridge, Gwendolyn Quinn, W. Hamish Wallace and Kutluk Oktay

Purpose: To update guidance for health care providers about fertility preservation for adults and children with cancer.

Methods: A systematic review of the literature published from March 2006 through January 2013 was completed using MEDLINE and the Cochrane Collaboration Library. An Update Panel reviewed the evidence and updated the recommendation language.

Results: There were 222 new publications that met inclusion criteria. A majority were observational studies, cohort studies, and case series or reports, with few randomized clinical trials. After review of the new evidence, the Update Panel concluded that no major, substantive revisions to the 2006 American Society of Clinical Oncology recommendations were warranted, but clarifications were added.

Recommendations: As part of education and informed consent before cancer therapy, health care providers (including medical oncologists, radiation oncologists, gynecologic oncologists, urologists, hematologists, pediatric oncologists, and surgeons) should address the possibility of infertility with patients treated during their reproductive years (or with parents or guardians of children) and be prepared to discuss fertility preservation options and/or to refer all potential patients to appropriate reproductive specialists. Although patients may be focused initially on their cancer diagnosis, the Update Panel encourages providers to advise patients regarding potential threats to fertility as early as possible in the treatment process so as to allow for the widest array of options for fertility preservation. The discussion should be documented. Sperm and embryo cryopreservation as well as oocyte cryopreservation are considered standard practice and are widely available. Other fertility preservation methods should be considered investigational and should be performed by providers with the necessary expertise.

Disclaimer: The clinical practice guidelines and other guidance published herein are provided by the American Society of Clinical Oncology, Inc. (“ASCO”) to assist practitioners in clinical decision making. The information therein should not be relied upon as being complete or accurate, nor should it be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. With the rapid development of scientific knowledge, new evidence may emerge between the time information is developed and when it is published or read. The information is not continually updated and may not reflect the most recent evidence. The information addresses only the topics specifically identified therein and is not applicable to other interventions, diseases, or stages of diseases. This information does not mandate any particular course of medical care. Further, the information is not intended to substitute for the independent professional judgment of the treating physician, as the information does not account for individual variation among patients. Recommendations reflect high, moderate or low confidence that the recommendation reflects the net effect of a given course of action. The use of words like “must,” “must not,” “should,” and “should not” indicate that a course of action is recommended or not recommended for either most or many patients, but there is latitude for the treating physician to select other courses of action in individual cases. In all cases, the selected course of action should be considered by the treating physician in the context of treating the individual patient. Use of the information is voluntary. ASCO provides this information on an “as is” basis, and makes no warranty, express or implied, regarding the information. ASCO specifically disclaims any warranties of merchantability or fitness for a particular use or purpose. ASCO assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of this information or for any errors or omissions.

Last updated 5/28/2013

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




Happy Mothers’ Day To All


Maternal bliss Copyright J. Pabon collection
Maternal bliss
Copyright J. Pabon collection

My sincere best wishes to all the Moms and Mothers to be.  Today is a special day about remembering and appreciating all that our mother s have done and do for us.

All the  Best!!


Dr. Pabon

Sarasota and Bonita Springs, Florida

Mother and children in Central Park copyright J. Pabon collection
Mother and children in Central Park
copyright J. Pabon collection

IVF NEWS: Low Sugar and Higher Protein Diet Boosts IVF Success

IVF success may be boosted by a protein rich and low sugar diet.  More and more medical scientists and physicians are recognizing that  the usual American diet that is rich on carbohydrates may be bad for your health.  More evidence is piling up regarding the inflammatory nature of sugar.  High sugar/carbohydrate consumption has been shown to elevate serum inflammatory markers like C-reactive protein.  Inflammation is being recognized at the basis of the pathophysiology of diseases like atherosclerosis.  More and more cardiologists are realizing that a low carbohydrate diet may be healthier.  Inflammation and high sugar levels may not be the optimal environment for the developing gametes and embryos.

Personally speaking, many of you know that I adhere to a low carb. lifestyle (not a diet).  Since I have changed my habits, my serum inflammatory markers have normalized as well as my cholesterol and triglyceride levels.  I have also lost a significant amount of weight.

I have been recommending  a lower carb and higher protein diet to my obese patients.  Some have lost more than 100 pounds by just following this simple advice:

Buy a good scale and weigh each morning.

Drink an 8-10 ounce glass of sugar-free metamucil each day.

Take a prenatal vitamin or multivitamin.

Stop eating sugar, bread, flour, flour products, pasta, potatoes, sweets, sweet fruits, yogurt, and cereals.

Instead eat protein rich low sugar/carbohydrate foods like meats, eggs, cauliflower, broccoli, cheeses, etc.

Have your doctor check your cholesterol levels before you begin and repeat them after a few weeks on the program.  You will be amazed.  The physiology of the weight loss effect has to do with the lower insulin levels and the higher glucagon levels that result from this diet.

Now, the research quoted below applies to even patients of normal weight.  Read on…

Low-Carb Diet Improves In Vitro Fertilization

By Kate Johnson/As published on Medscape.com

May 08, 2013


Reducing carbohydrates and boosting protein intake can significantly improve a woman’s chance of conception and birth after in vitro fertilization (IVF), according to a new study.

The effect is “at the egg level,” said lead investigator Jeffrey Russell, MD, from the Delaware Institute for Reproductive Medicine in Newark. He presented the findings here at American Congress of Obstetricians and Gynecologists 61st Annual Clinical Meeting.

Carbohydrate-loaded diets create a hostile oocyte environment even before conception or implantation, he explained.

“Eggs and embryos are not going to do well in a high-glucose environment.” By lowering carbs and increasing protein, “you’re bathing your egg in good, healthy, nutritious supplements,” he said.

Dr. Russell said this study was prompted by the poor quality of embryos he was seeing in young, healthy women who came through his IVF program. “We couldn’t figure out why. They weren’t overweight, they weren’t diabetic,” he said.

The 120 women in the study, who were 36 and 37 years of age, completed a 3-day dietary log. It revealed that for some, their daily diet was 60% to 70% carbohydrates. “They were eating oatmeal for breakfast, a bagel for lunch, pasta for dinner, and no protein,” Dr. Russell explained.

Patients were categorized into 1 of 2 groups: those whose average diet was more than 25% protein (n = 48), and those whose average diet was less than 25% protein (n = 72). There was no difference in average body mass index between the 2 groups (approximately 26 kg/m²).

There were significant differences in IVF response between the 2 groups. Blastocyst development was higher in the high-protein group than in the low-protein group (64% vs 33.8%; < .002), as were clinical pregnancy rates (66.6% vs 31.9%; < .0005) and live birth rates (58.3% vs 11.3%; < .0005).

When protein intake was more than 25% of the diet and carbohydrate intake was less than 40%, the clinical pregnancy rate shot up to 80%, he reported.

Dr. Russell now counsels all IVF patients to cut down on carbohydrate intake and increase protein intake.

“There is no caloric restriction, but they have to get above 25% protein. This is not a weight-loss program, it’s a nutritional program. This is not about losing weight to get pregnant, it’s about eating healthier to get pregnant,” he said.

Back to Basics

In a study presented at the American Society of Reproductive Medicine (ASRM) meeting last year, IVF patients who switched to a low-carbohydrate, high-protein diet and then underwent another cycle increased their blastocyst formation rate from 19% to 45% and their clinical pregnancy rate from 17% to 83% (Fertil Steril. 2012;98[Suppl]:S47).

Even non-IVF patients with polycystic ovarian syndrome have improved pregnancy rates after making this lifestyle change, Dr. Russell noted.

This “draws attention to a previously understudied area of reproduction…and opens the way for understanding a host of dietary factors that may be related to improved outcomes in the assisted reproductive technologies,” ASRM president-elect Richard Reindollar, MD, who is chair of obstetrics and gynecology at the Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, told Medscape Medical News.

“These studies demonstrate how little we know about the effect of micronutrients in our diets on various aspects of reproduction. They demonstrate a field wide open for future research and beg questions such as whether, for example, it is carbohydrates in general or the inflammatory effects of gluten in grain carbohydrates that are deleterious to IVF outcomes,” said Dr. Reindollar.

The study’s connection between high blood glucose to IVF success is “an interesting finding that deserves to be evaluated further,” said Sharon Phelan, MD, from the University of New Mexico in Albuquerque, who is a member of the ACOG Scientific Program Committee. She was asked by Medscape Medical News to comment on the findings.

“Although the blood glucose is not high enough to be in the diabetic range, it is enough to be toxic to the developing blastocyst,” she added.” Perhaps this is a call for us to get back to our ‘roots,’ or basic diets, again.”

Dr. Russell, Dr. Reindollar, and Dr. Phelan have disclosed no relevant financial relationships.

American Congress of Obstetricians and Gynecologists (ACOG) 61st Annual Clinical Meeting: Abstract 96. Presented May 6, 2013.

All the Best,


Julio E. Pabon, M.D.IMG_0440

Medical and Laboratory Director

Fertility Center and Applied Genetics of Florida

Sarasota and Bonita Springs, Florida, U.S.A.



Fertility Patients With Early Pregnancy Nausea

Here is a new product that can help patients feel better in early pregnancy.  I only wish the name was easier to remember. They should of named it something like nausearx or help-u-eat-better pill.  Anyway.  Here is the info:

FDA approves Diclegis for pregnant women experiencing nausea and vomiting

The U.S. Food and Drug Administration today approved Diclegis (doxylamine succinate and pyridoxine hydrochloride) to treat pregnant women experiencing nausea and vomiting.
Diclegis is a delayed-release tablet intended for women who have not adequately responded to conservative management of nausea and vomiting during pregnancy, such as dietary and lifestyle modifications. These modifications include eating several small meals instead of three large meals, eating bland foods that are low in fat and easy to digest and avoiding smells that can trigger nausea.
“Many women experience nausea and vomiting during pregnancy, and sometimes these symptoms are not adequately managed through recommended changes in diet and lifestyle,” said Hylton V. Joffe, M.D., M.M.Sc., director of the Division of Reproductive and Urologic Products in the FDA’s Center for Drug Evaluation and Research. “Diclegis is now the only FDA-approved treatment for nausea and vomiting due to pregnancy, providing a therapeutic option for pregnant women seeking relief from these symptoms.”
Diclegis was studied in 261 women experiencing nausea and vomiting due to pregnancy. Study participants in the clinical trial were at least 18 years old and had been pregnant for at least 7 weeks and up to 14 weeks. Women were randomly assigned to receive two weeks of treatment with Diclegis or a placebo. The study results showed that women taking Diclegis experienced greater improvement in nausea and vomiting than those taking placebo. Additionally, observational (epidemiological) studies have shown that the combination of active ingredients in Diclegis does not pose an increased risk of harm to the fetus.
Diclegis is taken daily. Tablets must be taken whole on an empty stomach. The recommended starting dose is two tablets taken at bedtime. If symptoms are not adequately controlled, the dose can be increased to a maximum recommended dose of four tablets daily (one in the morning, one mid-afternoon and two at bedtime).
Nausea and vomiting due to pregnancy usually improve after the first trimester. Health care professionals should reassess their patients for continued need for Diclegis as pregnancy progresses.
Drowsiness or sleepiness, which can be severe, is the most common side effect reported by women taking Diclegis. Women should avoid using Diclegis when engaging in activities requiring mental alertness, such as driving or operating heavy machinery, until cleared to do so by their health care provider.
Diclegis is marketed by Duchesnay Inc., based in Blainville, Québec, Canada.

All the Best!

Julio E. Pabon, M.D.

Bonita Springs and Sarasota, Florida

copyright J. Pabon collection
copyright J. Pabon collectionSarasota and Bonita Springs, Florida, U.S.A.