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Fertility, IVF and Egg Donation
by Dr. Mohamad Irani on Apr.02, 2019, under Chromosomal Abnormalities in Eggs, Embryo implantation, IVF success rates, Miscarriage, Number of IVF Embryos to Transfer, Preimplantation Genetic Screening, Single Embryo Transfer
It has been an exciting time for the field of Reproductive Medicine, which has witnessed major advances over the last three decades. For instance, the recent evolution in Preimplantation Genetic Testing for aneuploidy (PGT-A, formerly called Preimplantation Genetic Screening [PGS]), has provided an important tool to enhance embryo selection and subsequently elective single embryo transfer (eSET).
Advancements of Preimplantation Genetic Testing for Aneuploidy (PGT-A)
Embryo biopsy on Day 3 has been suggested to adversely affect the implantation potential of the embryo. Hence, the majority of IVF laboratories have switched to blastocyst biopsy on Day 5 or 6. Evidence supports that the improvements in the biopsy technique, and the removal of approximately 4-5 cells from the trophectoderm (precursors to the placenta) on Day 5, when performed by expert embryologists, may not negatively impact the reproductive potential of the embryo.
Furthermore, enhancements to genetic testing, which currently analyzes all chromosomes compared to the initial platform that analyzed only a limited number of chromosomes, have significantly improved the accuracy of the test.
Clinical Benefits of PGT-A
This technology has significantly decreased miscarriage rates and increased the implantation rate per transfer. The high implantation potential of embryos determined to be euploid by PGT-A has contributed to the increased adoption of elective single embryo transfer, (eSET). This has subsequently reduced the incidence of multiple gestations, and all associated maternal and fetal complications.
Despite its critical advantages, PGT-A comes with some risks and may not be the best option for all patients; therefore, personalization of care is key to success. All patients should understand the pros and cons of each procedure in order to make informed decisions.
In my practice, I help patients understand the advanced reproductive technologies that offer them their best chance of achieving a healthy baby.
The Society for Assisted Reproductive Technology (SART) has released the 2014 IVF success rate report in 2016. The SART in vitro fertilization outcome reports have been coming out annually for over 15 years. We are proud of our consistently high success rates. We encourage people to examine both our IVF success rates and our egg donation success rates and compare them to the national averages as well as to those of other clinics they might consider.
This year’s report represents a significant change in the way the data is reported as compared to the past. SART is trying to make the report more representative of IVF outcomes as they relate to the current styles of practice in IVF centers in the US.
In the past the SART report showed the IVF outcome data on a per started cycle, per egg retrieval, and per embryo transfer basis. However, this has basically been done away with in the 2014 report. The new SART report organizes IVF outcome metrics differently.
I will review some of the main highlights of the new report using screen shots from our own clinic’s 2014 SART report that can be found online at:
The first section in the outcome tables shows what start calls the Preliminary Cumulative Outcome per Intended Egg Retrieval. The intention is to show the cumulative chance for having a baby from both the primary embryo transfer procedure and any also any subsequent embryo transfers using frozen eggs or embryos that were not transferred initially.
I think it is unfortunate that SART put this table at the top of the report. It makes it seem that this is the most important outcome metric. However, there are problems with this metric including the fact that any embryo transfers with subsequent live births that do not fall within that calendar year will not be included in the cumulative outcome.
SART is extremely focused on singleton pregnancy outcomes. Many couples with infertility are much less focused on avoiding twins. The SART report highlights the singleton line in green. I have highlighted the live birth line in red. This line shows the cumulative live birth rate per intended egg retrieval. In my opinion the live birth rate is also important for couples struggling with infertility.
The next table is referred to by SART as the Preliminary Primary Outcome per Intended Retrieval. The preliminary primary outcome is the outcome of the first embryo transfer following the egg retrieval.
- Therefore, if there is a fresh embryo transfer that is done several days after the egg retrieval that outcome would be the preliminary primary outcome.
- However, if all of the embryos from that egg retrieval were frozen and none were transferred fresh – then the first frozen embryo transfer cycle would give the preliminary primary outcome.
- If all embryos were frozen from the fresh egg retrieval and preimplantation genetic screening (PGS) was performed and all PGS results were abnormal resulting in no frozen embryo transfer – then the outcome is a failed cycle at that point.
This change in outcome metrics was put into place by SART because in recent years some clinics have moved more to performing frozen embryo transfers and are doing more “freeze all” cycles. In a freeze all cycle, all embryos are frozen several days after the egg retrieval and then thawed and transferred in a subsequent cycle. I think that SART should have put this table at the top of the page.
Again, I have highlighted the live birth row which I believe is important in red in contrast to what SART is highlighting in green.
The next table is for what SART refers to as Preliminary Subsequent Outcomes (frozen cycles). SART defines this as cycles using any frozen thawed eggs or embryos after there has already been a primary outcome. So for the most part this table represents the frozen embryo transfer success rates for the clinic. However, it excludes frozen embryo transfers that would have been the primary embryo transfer (from freeze all cycles).
The next table SART calls the Preliminary Live Birth per Patient. This table is reporting outcomes only for those patients who are new to that specific clinic and starting their first cycle for egg retrieval during that year. I have no idea why SART thinks that this is an important metric and deserving of its own table.
The last 4 tables on the page of the new SART report are for donor eggs and donor embryos. There is a table for live birth outcomes using fresh donor eggs, another table for frozen donor eggs, then frozen thawed embryos from donor eggs, and finally a table for transfers using donated embryos. These tables are easier to understand because they do not follow the “preliminary” and “subsequent” outcome methodology that SART now uses for the cycles performed using a woman’s own eggs.
There are some interesting and potentially useful features built into the new report. For example, the report now allows the viewer to apply filters to the data set. For example, you can filter frozen embryo transfer cycles to see only those results that had preimplantation genetic screening (PGS) performed on the embryos. Other filters can be applied as well.
SART is an organization of medical and other professionals. SART members are from academic medical centers and also from private practice fertility clinics. SART members could be fertility doctors, nurses, embryologists, lab directors, mental health professionals, attorneys that specialize in reproductive law, and others.
SART members have different agendas depending on the details of their own organizations and business models. Therefore, SART will be pulled in different directions by members with their own agendas. Such a varied organization will never be able to please all members. The major changes in the 2014 SART report seems to have been done in an effort to satisfy some factions within the organization. However, that has led to some problems with the report.
I have been working as a fertility doctor for over 20 years and during that time have used databases and spreadsheets on a daily basis. Understandably, I am very familiar with IVF outcome measures. However, this report was confusing for me until I studied it carefully. It took some time to figure it out. Therefore, I think that this report will be very difficult (or impossible) for the average infertility patient to understand well.
If the 2014 SART report satisfies some SART members regarding their gripes about past year’s reports then maybe it serves the SART organization’s agenda. Overall, I think it is a work in progress.
Do IVF frozen embryo transfer (FET) cycles have increased success rates or other benefits as compared to fresh transfers?
Over the past several years there have been several studies published that investigated whether fresh or frozen transfers result in higher IVF pregnancy success rates and also which type of transfer is associated with healthier outcomes for mothers and babies.
In fact, some IVF programs have completely stopped doing fresh embryo transfers and are only performing frozen embryo transfers. As of now (summer 2016), the IVF field in the US seems to be slowly moving toward doing more frozen embryo transfers and less fresh transfers. This might be a long-term trend that could help us achieve the most successful treatment outcomes.
There are 2 general issues related to the possible superiority of frozen embryo transfer as compared to fresh transfer.
- The rate of implantation could be reduced in fresh transfers as compared to frozen embryo transfers.
- There could be a “healthier” implantation process in FET cycles with development of a better connection between the placenta and the mother. This could potentially result in benefits at multiple levels.
Over the last 10 years or so embryo freezing and thawing efficiency has improved dramatically with widespread use of vitrification (ultra-rapid freezing) vs. the older slow freezing method. This led to much better pregnancy success rates with frozen embryos than we saw in the past. Now some fertility specialists are claiming that frozen embryo transfers actually give higher success rates than fresh transfers.
Embryo implantation with a frozen cycle could be better with the more “natural” hormone environment in the uterus. The uterine lining in a fresh cycle with ovarian stimulation is exposed to unnaturally high levels of the reproductive hormones estrogen and progesterone which could deter effective embryo implantation.
Some of the studies done so far show significantly higher pregnancy rates with frozen embryo transfers as compared to fresh embryo transfers. However, other studies have shown no significant difference in success rates between fresh and frozen transfers.
One problem is that there are several variables that are difficult to control for in order to have the proper study design to answer this question. Overall, at this point the evidence suggests that frozen transfers seem to have somewhat higher pregnancy rates as compared to fresh transfers.
Further studies should be done to confirm (or deny) this and also to investigate whether there are subsets of patients that benefit more than others by having their transfer “deferred” to a frozen cycle. It is possible that some patients would get a large increase in their chances for pregnancy with an FET and others would get little or no benefit at all. We just don’t know enough yet.
For example, several studies that have shown that IVF patients that take a “pure” Lupron trigger (without any HCG trigger) have better pregnancy rates in an FET cycle vs. with fresh transfer. However, the magnitude of the difference is debatable and in many clinics (ours included) it is a relatively small percentage of the patients that get a pure Lupron trigger.
This issue is about ovarian hyperstimulation syndrome, OHSS. Mild ovarian hyperstimulation is fairly common with IVF and is not a major medical problem. It goes away fairly quickly and has no major consequences. However, severe OHSS is serious and needs to be avoided.
By utilizing a pure Lupron trigger (also called an agonist trigger) severe OHSS can be completely avoided. However, some IVF patients do not get a pure Lupron trigger (they took some HCG at trigger time) and these women might become significantly hyperstimulated if they become pregnant from a fresh embryo transfer. These women should have their embryos frozen and then later thawed and transferred (FET) after the hyperstimulated ovaries regress to normal.
Tubal pregnancy rates
There is some evidence from retrospective studies that ectopic pregnancies are more common after fresh as compared to frozen embryo transfers. For example, one study reported ectopic pregnancies occurring in 4.6% of clinical pregnancies after fresh transfers and 2.2% of clinical pregnancies after frozen transfers. Some other studies have shown smaller differences.
Obstetric and perinatal outcomes
So far, the studies on health outcomes for mothers and babies after fresh vs. frozen embryo transfers show mixed results. Overall, it seems that there might be more healthy outcomes after FET as compared to after a fresh transfer. However, more research is needed in this area. The list below summarizes results from some recent studies.
- The risk for a baby to have low birth weight is increased after fresh compared to frozen transfers (favors doing FET)
- The risk for having a preterm birth is increased after fresh compared to frozen transfers (favors doing FET).
- The risk for having placenta accreta (placenta attached deeply in uterine wall and difficult to separate at delivery) seems to be increased in frozen as compared to fresh embryo transfers (favors doing fresh transfer).
- The risk for having a large for gestational age baby seems to be increased in frozen as compared to fresh embryo transfers (favors doing fresh transfer).
There is some evidence that pregnancy rates are somewhat higher and overall outcomes may be better for pregnancies with frozen transfers compared to with fresh transfers. However, as discussed above, some of the outcome data shows pros and cons for FETs.
Other important questions are how much better will these outcomes be, and how much extra will it cost with switching from fresh embryo transfers to FETs? Then, couples (and their doctors) must decide whether that additional benefit is worth that extra cost.
That question will not have the same answer for every couple because financial resources and insurance coverage varies between couples. If patients have excellent insurance coverage that will pay for multiple cycles of fresh and frozen embryo transfers then the economic decision for a couple could be easy. However, few people have insurance coverage like that.
The debate about these issues continues in our field of medicine. There are important questions to answer and well designed studies are needed. In the meantime we try to make the best decisions with our patients on a case by case basis.
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Advanced Fertility Center of Chicago
Richard Sherbahn, MD is a Board Certified Reproductive Endocrinology and Infertility specialist.
Dr. Sherbahn founded the Advanced Fertility Center of Chicago in 1997.
He will post regularly about fertility issues.
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