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Archive for the ‘blastocyst embryos’ 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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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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Figuring out YOUR Odds of a Live Birth With IVF

By David Kreiner MD, and Tracey Minella

July 2nd, 2012 at 8:35 am

 

 

Statistics can be confusing. And when you’re on fertility meds and your hormones are raging, it can be hard to think clearly. So grab a cup of coffee and your thinking cap because you’re going to be interested in this post from Dr. Kreiner.

It’s about a recent study published in the New England Journal of Medicine that finally sheds light on a woman’s odds of having a live birth from IVF. The study examined data from SART (Society for Assisted Reproductive Technology), the primary organization that collects data, sets the guidelines, and helps maintain the standards for the practice of assisted reproductive technologies.

Dr. Kreiner reports:

NEJM Study Uses SART Data to Determine Cumulative Birth Rates for Individual Patients with In Vitro Fertilization

A new study published in the New England Journal of Medicine links data from the SART Clinic Outcome Reporting System to individual women who underwent cycles from 2004 to 2009.  In this way a cumulative live birth rate over the course of all their cycles could be determined.

The researchers reviewed data from 246,740 women, with 471,208 cycles and 140,859 live births, found that live-birth rates declined with increasing maternal age and increasing cycle number when patients’ own oocytes were used, but live-birth rates remained high in donor egg cycles. See Luke et al, Cumulative Birth Rates with Linked Assisted Reproductive Technology Cycles, N Engl J Med 2012; 366:2483-2491 June 28, 2012. http://www.nejm.org/doi/full/10.1056/NEJMoa1110238

By the third cycle, the conservative (patients who underwent fewer than three cycles were assumed not to get pregnant) and optimal estimates of live-birth rates (patients with fewer than three cycles were assumed to have a live birth) with autologous oocytes had declined from 63.3% and 74.6%, respectively, for women younger than 31 years of age to 18.6% and 27.8% for those 41 or 42 years of age and to 6.6% and 11.3% for those 43 years of age or older. When donor oocytes were used, the rates were higher than 60% and 80%, respectively, for all ages. Rates were higher with blastocyst embryos (day of transfer, 5 or 6) than with cleavage embryos (day of transfer, 2 or 3).

At the third cycle, the conservative and optimal estimates of cumulative live-birth rates were, respectively, 42.7% and 65.3% for transfer of cleavage embryos and 52.4% and 80.7% for transfer of blastocyst embryos when fresh autologous oocytes were used.

The study looks for the first time at a “cumulative live birth rate” for each patient going through three embryo transfers. They provide a range based on those patients who did not proceed with subsequent cycles assuming no pregnancy for lower end and live birth in upper end. They do not go into number of embryos transferred or multiple pregnancies.  This provides the best data we have available to answer the question of what the odds are that a patient will experience a successful live birth with IVF.  Understanding that the data is now a little dated and represents a national average, my expectation is that on the average we should see even somewhat better success.

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What did you think of the study? Any questions? Ask Dr. Kreiner right here.

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