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Archive for the ‘ASRM’ tag

Sunshine, Vitamin D, and Your Fertility

By Dr. David Kreiner and Brianna Rudick, MD

May 27th, 2014 at 3:02 pm



image courtesy of victor Habbick/

Vitamin D is a fat soluble vitamin that is present in a variety of forms but has recently been recognized as playing a critical role in reproduction.  It is essential in the production of sex hormones in the body.  It is thought that a deficiency of Vitamin D may lead among other things to ovulation disorders.

It has been demonstrated that Vitamin D deficient rats had a 75% reduced fertility and a 50% smaller litter size that was corrected with Vitamin D treatment.  In addition, sperm motility in males was reduced in the presence of a Vitamin D deficiency.

A recent study at the Yale University School of Medicine revealed that only 7% of 67 infertile women studied had normal Vitamin D levels and not a single woman with an ovulatory disorder had normal levels.  Nearly 40% of women with ovulatory dysfunction had a clinical deficiency of Vitamin D.

At an American Society of Reproductive Medicine conference, a study presented by Dr. Briana Rudick from USC showed that a deficiency of Vitamin D can also have a detrimental effect on pregnancy rates after IVF, possibly through an effect on the endometrial lining of the uterus.   In her study only 42% of the infertile women going through IVF had normal Vitamin D levels.  Vitamin D levels did not impact the number of ampules of gonadotropin utilized nor the number of eggs stimulated, embryos created or embro quality.  However, Vitamin D levels did significantly affect pregnancy rates even when controlled for number of embryos transferred and embryo quality.  In this study the pregnancy rate dropped from 51% in Caucasian women undergoing IVF who had normal Vitamin D levels to 44% in those with insufficient levels and 19% in those that were deficient.

Vitamin D deficiency has also been associated with poor pregnancy outcomes including preeclampsia and gestational diabetes.

Vitamin D can be obtained for free by sitting out in the sun and getting sun exposure on the arms and legs for 15-20 minutes per day during peak sunlight hours.  The sunlight helps the skin to create Vitamin D3 that is then transformed into the active form of Vitamin D by the kidneys and liver.   An oral supplement is available also in the form of Vitamin D3, with a minimum recommended amount of 1000 IU a day for women planning on becoming pregnant.  For those with clinical insufficiencies a higher dose may be administered by injection.

Our study and many others suggest that the effect is endometrial, but we don’t know for sure.

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Did you know that Vitamin D deficiency can affect your fertility? Do you know if you are deficient?  

*****Note that if you’re thinking of sitting outside without sunscreen now that the sun is scorching hot, please check with your doctor first for guidelines on how much time, if any, he or she recommends you spending outside with minimal or no sunscreen. It is not for everyone. And you can burn even when it’s cloudy.

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Infertility Podcast Series: Journey to the Crib: Chapter 20: Co-Culture of Embryos

By David Kreiner, MD

June 24th, 2013 at 9:34 pm


Welcome to the Journey to the Crib Podcast.  We will have a blog discussion each week with each chapter.  This podcast covers Chapter twenty: Co-culture of Embryos. You, the listener, are invited to ask questions and make comments.  You can access the podcast here:

Co-Culture of Embryos

Co-Culture is a procedure whereby “helper” cells are grown along with the developing embryo.  The most popular cell lines include endometrial cells (from the endometrium or uterine lining) and cumulus cells from a woman’s ovaries.  Both cell lines are derived from patients.  Endometrial cells are more difficult to obtain and process, while cumulus cells are routinely removed along with the oocytes during the IVF retrieval.

Cumulus cells play an important role on the maturation and development of oocytes.  They produce hyaluronan which is normally involved in cell adhesion, growth and development in the body and is found in the uterus during implantation.

Co-culture of cumulus cells provides an opportunity to detoxify the embryo’s culture medium that the embryos are grown in and produce growth factors important for cell development.

Performing co-culture of embryos has improved implantation and pregnancy rates as presented by us at the national meeting of the American Society of Reproductive Medicine in 2007.

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Was this helpful in answering your questions about co-culture of embryos?

Please share your thoughts about this podcast here. Ask any questions an Dr. Kreiner will answer.

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Report From The 2010 American Society for Reproductive Medicine Meeting

By Dr. David Kreiner

November 10th, 2010 at 10:58 pm

It has been two weeks since my return from this year’s national fertility meeting, the ASRM (American Society for Reproductive Medicine) which was held in Denver this year.  It is the time and place that breakthroughs in fertility care are announced, results of research studies are discussed, problems and issues of the day are hammered out.

A few national trends were evident throughout the meeting.  Single embryo transfer is becoming common place and successful.  In some studies, it was as reliable as double embryo transfer in obtaining a baby.  Noteworthy, was a study out of the Cornell program which attempted to dispute the previously reported increase in pregnancy complications associated with IVF pregnancies.  They showed in their study that when only one embryo was transferred there was no increase in preterm birth complications.  They proposed that multiple embryo transfers perhaps with multiple implantations that spontaneously reduce to singletons are the cause for the reported increase in IVF pregnancy complications supposedly seen in singleton pregnancies.  This was yet another argument in addition to reducing the risk to multiple pregnancies proposed for transferring a single embryo at a time. 

Questions were raised as to how to motivate patients to transfer only one embryo at a time.  In addition to education, the concept at East Coast Fertility that is to offer those who transfer one at time free cryopreservation, storage and frozen embryo transfers was being practiced currently by at least one other program.  I believe we will be hearing next year that this became a nationwide practice.

There were several studies showing excellent success with minimal stimulation IVF.  Program directors actively providing minimal stimulation IVF complained that no distinction was made in the SART reporting so that the lower pregnancy rates seen with minimal stimulation still hurt those programs’ pregnancy statistics.   Hopefully, this much less expensive, less invasive, safer alternative will be evaluated separate from full stimulation IVF so programs that offer this service to patients are not discriminated against for doing so.

Perhaps the most exciting advance I heard about during the meeting was the improved pregnancy rates and diminished miscarriage rates seen with the 24 chromosome analysis preembryo genetic diagnosis.  This was being offered at the Blastocyst stage to improve cost effectiveness and reduce error and injury to the embryo.  If this holds up then the promise of improving pregnancy rates of a single embryo transfer known to be genetically normal will become the standard of care not just improving the efficiency of IVF but perhaps making it as safe as a naturally conceived pregnancy

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Will IVF Work For Me?

By Dr. David Kreiner

July 13th, 2010 at 12:00 am

What everyone wants to know when they decide to look into invitro ferilization (IVF) as a treatment option is "what is my chance for success?"  It’s a complicated question and the answer varies from  patient to patient. But let me try to break down a little bit for you.

In 2002 about 28% of cycles in the United States in which women underwent IVF and embryo transfer with their own eggs resulted in the live birth of at least one infant. This rate has been improving slowly but steadily over the years.  Patients should be aware, however, that some clinics define "success" as any positive pregnancy test or any pregnancy, even if miscarried or ectopic. These "successes" are irrelevant to patients desiring a baby. To put these figures into perspective, studies have shown that the rate of pregnancy in couples with proven fertility in the past is only about 20% per cycle. Therefore, although a figure of 28% may sound low, it is greater than the chance that a fertile couple will conceive in any given cycle.

Success varies with many factors. The age of the woman is the most important factor, when women are using their own eggs. Success rates decline as women age, and success rates drop off even more dramatically after about age 37. Part of this decline is due to a lower chance of getting pregnant from ART, and part is due to a higher risk of miscarriage with increasing age, especially over age 40. There is, however, no evidence that the risk of birth defects or chromosome abnormalities (such as Down’s syndrome) is any different with ART than with natural conception.

Success rates vary with the number of embryos transferred. However, transferring more embryos at one time not only increases the chance of success with that transfer, but will also increase the risk of a multiple pregnancy, which are much more complicated than a singleton pregnancy. The impact of the number of embryos that are transferred on success rates also varies with the age of the woman.

Pregnancy complications, such as premature birth and low birth weight, tend to be higher with ART pregnancies, primarily because of the much higher rate of multiple pregnancies. Nationally, in 2002-2003 about 30% of ART deliveries were twin deliveries, versus 1-2% of spontaneous pregnancies. The risk of pregnancy containing triplets or more was 6% in 2003.

As women get older, the likelihood of a successful response to ovarian stimulation and progression to egg retrieval decreases. These cycles in older women that have progressed to egg retrieval are also slightly less likely to reach transfer.  The percentage of cycles that progress from transfer to pregnancy significantly decreases as women get older.  As women get older, cycles that have progressed to pregnancy are less likely to result in a live birth because the risk for miscarriage is greater.  This age related decrease in success accelerates after age 35 and even more so after age 40.  Overall, 37% of cycles started in 2003 among women younger than 35 resulted in live births. This percentage decreased to 30% among women 35–37 years of age, 20% among women 38–40, 11% among women 41–42, and 4% among women older than 42.  The proportion of cycles that resulted in singleton live births is even lower for each age group.

The success rates vary in different programs in part because of quality, skill and experience but also based on the above factors of age, number of embryos transferred and patient population.  Patients may also differ by diagnosis and intrinsic fertility which may relate to the number of eggs a patient may be able to stimulate reflected by baseline FSH and antral follicle count as well as the genetics of their gametes.  These differences make it impossible to compare programs.

Another factor often overlooked when considering one’s odds of conceiving and having a healthy baby from an IVF procedure is the success with cryopreserved embryos.

Thus, a program which may have a lower success rate with a fresh transfer but much higher success with a frozen embryo transfer will result in a better chance of conceiving with only a single IVF stimulation and retrieval.  Success with frozen embryos transferred in a subsequent cycle also allows the program to transfer fewer embryos in the fresh cycle minimizing the risk of a riskier multiple pregnancy.  It may be more revealing to examine a program’s success with a combination of the fresh embryo transfer and frozen embryo transfers resulting from a single IVF stimulation and transfer.  For example, at East Coast Fertility, the combined number of fresh and frozen embryo transfers that resulted in pregnancies for women under 35.from January 1, 2002 to December 2008 was 396.  The number of retrievals during that time was 821.  The success rate combining the fresh and frozen pregnancies divided by the number of retrievals was 61%.  The high frozen embryo transfer pregnancy rate allowed us to transfer fewer embryos so that there were 0 triplets from fresh transfers during this time.

What can I do to increase my odds?

Patients often ask if there are any additional procedures we can do in the lab that may improve the odds of conception.  Assisted hatching is the oldest and most commonly added procedure aimed at improving an embryo’s ability to implant.  Embryos must break out or hatch from their shell that has enclosed them since fertilization prior to implanting into the uterine lining.  This can be performed mechanically, chemically and most recently by utilizing a laser microscopically aimed at the zona pellucidum, the shell surrounding the embryo.  Assisted hatching appears to benefit patients who are older than 38 years of age and those with thick zonae.

Recently a protein additive called “Embryo glue” was shown to improve implantation rates in some patients whose embryos were transferred in media containing “Embryo glue”.  Time will tell if the adhesive effect of this supplement is truly increasing success rates and warrants wide scale use in IVF programs.

Embryo co culture is the growth of developing embryos is the same Petri dish as another cell line.  Programs utilize either the woman’s endometrial cells obtained from a previous endometrial biopsy or granulosa cells obtained at the time of the egg retrieval from the same follicles aspirated as the eggs.  Growth factors produced by these endometrial and granulosa cell lines diffuse to the developing embryo and are thought to aid in the growth and development of the embryo.  It appears to help patients who have had previous IVF failures and poor embryo development.

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