Common practices of the best IVF programs

September 10, 2010Carole 12 Comments »

I was happy to find an article in Fertility and Sterility which held more than academic interest to IVF geeks like me but might be directly useful to patients. In their article entitled “What do consistently high-performing in vitro fertilization programs in the US do? “, four IVF providers (Dr. Bradley J. Van Voorhis and Amy Sparks, PhD at the Dept. Ob/Gyn at University of Iowa Carver College of Medicine, Dr. Mika Thomas of Dallas-Fort Worth Fertility Associates and Dr. Eric S. Surrey from the Colorado Center for Reproductive Medicine) polled ten IVF clinics that were consistently high-performing IVF programs in the US. They didn’t reveal the names of these top performers because they wanted to focus on identifying best practices and not providing advertising for these programs.

Their method. They sent a 15 page best practice questionnaire to 12 programs who were consistently present in the top 25 IVF clinics who reported their results to the CDC in 2005 and 2006. Of these 12, ten responded. Programs were excluded if they did not perform at least 100 cycles per year for women in the youngest age group, under 35 years of age. Singleton delivery rate per cycle was the outcome data used to identify the best programs.

About the ten best clinics. These clinics had an average live birth rate per cycle in 2006 of 52% compared to 39% for all reporting programs. The authors note that the range of success rates (live birth per cycle) for all programs reporting in 2007 in the youngest age group of a patients (under 35 years of age who should have the best prognosis) was between 9 percent and over 50%!! Nine percent. That’s not a typo. This is why I urge all my readers to check the CDC reported rates for any program they are considering for IVF services.  Forty percent is acceptable, especially if there is no patient selection against hard patients. Fifty percent is good. Over 50% is the target. A nine percent pregnancy rate is simply not defensible.

THE RESULTS:

The best programs diagnose ovarian reserve. In order to customize the stimulation and treatment to the patient, doctors need to find out where you are in the pre-menopause, in menopause and post-menopause stages of egg quality and supply. As a natural result of aging, the quantity and quality of our eggs decrease. Sometimes, this decrease is more rapid than expected for our chronological age. Tests used to estimate ovarian reserve include number of follicles visible by ultrasound (100% of top ten clinics did this), blood test for follicle stimulating hormone (FSH) levels on day 3 of the cycle (90% used this), test for anti-Mullerian hormone (30%) and Clomid challenge test (20% in older women only). Finding out that your ovarian reserve is low may mean that your stimulation may be more aggressive or you will be directed to donor egg sooner rather than later. Better diagnosis up front should minimize the number of ineffective treatments you endure.

Weight exclusion for treatment. Forty percent of the top ten programs excluded women from IVF treatment if their body mass index (BMI) suggested morbid obesity. A BMI greater than 30 was used by two clinics, another used BMI greater than 35 and one used a weight greater than 136 kilograms or around 300 pounds. This may seem really discriminatory and mean at first look but actually it is not counter to the patients best interests. If a woman is morbidly obese, she is far less likely to conceive using IVF. if she does conceive, she is more likely to lose the baby, suffer pregnancy complications and may even damage her own health and lose her life. So the program that accepts everyone into their program is not doing those patients a favor, but they are raising revenue. Studies looking at  bariatric surgery and weight loss before IVF are encouraging.

Best clinics evaluate the uterine cavity to make sure it is implantation-ready. Saline infusion sonography (SIS)  is a test used to evaluate the uterine cavity. The uterus and tubes are filled with saline and ultrasound imaging is used to look inside the uterus and tubes to see if all’s clear. Inserting a tiny camera to look directly at the uterine lining is another way to check the uterus in a surgical procedure called  hysteroscopy. If endometrial (uterine lining)  polyps are found, 60% of the clinics will remove them, the rest of the clinics will remove them if they are of a certain size. Similarly, if submucousal (deeper level) fibroids are found, 70% will always remove them, 30% will remove them selectively. Sometimes the Fallopian tubes balloon with retained fluid to form an abnormal tube called a hydrosalpinge. Removal of hydrosalpinges has been found to benefit IVF outcomes in some cases. Large hydrosalpinges are routinely removed by surgery in all the top ten clinics. Smaller ones are removed by 40% and left in place by 60%.

A mock transfer is performed by all top clinics. To get an idea of how easy it will be to thread a catheter containing embryos through your cervix and into the uterus, doctors will perform a practice transfer using saline before the real deal. Top ten clinics always practiced their ET technique and 90% did this practice before they even started the stimulation to get early warning of special challenges in anatomy or nervous response that may be present at transfer.

Ovarian Stimulation practices. Top clinics had three types of protocols in their bag of tricks, long luteal phase GnRH agonist protocol, microdose flare GnRH agonist protocol and GnRH antagonist protocol. Eighty percent of top clinics reported a step-down in their dosing as the cycles progressed. Most clinics liked to use a combination of FSH and luteinizing hormone (LH) or a LH-like hormone called human chorionic gonadotropin (hCG) to optimize response. Starter doses ranged from 150IU per day to 300 per day. Some clinics use single injections per day and others preferred two half-dose injections per day. Metformin was used by all clinics for PCOS patients and half of the clinics used it for obese or insulin-resistant patients.

Measuring Ovarian Response. Every top clinic measured E2 blood levels and monitored follicle growth by ultrasound. Some also measured progesterone levels (50%), LH (40%) and FSH (20%). The number and kind of tests that are performed are hotly debated in the medical community have heard some doctors dismiss testing of P4, LH and FSH as having no value except in generating revenue. Other docs make decisions (usually to cancel a cycle) based on these other tests. Four to six testing events over the cycle or a test every 2-3 days is pretty typical according to the report of top clinics. Top clinics canceled cycles if less than 3-5 follicles were generated. The time to give hCG depended on the size of the biggest two follicles reaching an average size of 18 mm or greater (range 17mm to greater than 20mm). Oocyte retrieval was scheduled for 34-36 hours later and 60% of clinics performed the procedure at 36 hours.

Retrieval Best Practices. All top clinics used a propofol- or fentanyl-based anesthetic and 40% used Versed. Most top clinics (60%) used single lumen needles and the rest used a mixture of single lumen and double lumen needles. Double lumen needles are usually used to run flush fluid through the follicle after suction to rinse out the follicle and any sticky eggs.

Embryo Transfer best practices. 80% of top clinics use ultrasound imaging during the transfer to guide placement of the embryo in the uterus. Of the remaining 20%, 10% never use it and 10% only use it for the most difficult transfers. In high volume centers, I can believe that doctors get so experienced that they can do the transfer by feel but IMHO, doctors just learning to perform embryo transfers need that extra edge of being able to see where they are going. Eighty percent of top clinics load bubble into the catheter so that it can be visualized on the ultrasound. When your doctor says, “Can you see your embryos being deposited here? ” during the ultrasound, he is really pointing out the marker bubbles that are on either side of your embryos in the catheter. This little deception always annoyed me but why ruin a perfect Kodak moment?

Progesterone supplementation after transfer. All top clinics give progesterone (luteal phase hormonal support) after the transfer. Half use estrogen supplements also in all patients, 30% use estrogen only in the poor responders. Discontinuation of support varied widely with some clinics discontinuing support at the pregnancy test, others discontinuing support at 12 weeks of pregnancy.

IVF lab best practices.  ICSI was used selectively by top clinics although the middle level of usage reported (the median) was 60% of cases. Best IVF programs cultured their embryos in groups using microdrops of culture medium. This approach is based on scientific data suggesting the group culture is beneficial due to growth factors produced by the embryos. Measuring the ph of culture medium to determine if the delivery rate of CO2 into the incubator needs to be adjusted. In the old days, we adjusted our incubators to deliver 5% Co2 as measured by the sensors in the incubator. Although the point of adjusting the CO2 is to make the medium stable at a desired pH,  we never completed the loop and checked the actual pH achieved in the medium after equilibration in the incubator. When we did that, we realized that the CO2 sensor wasn’t always a reliable endpoint. The best labs recognize this and check the pH directly.  Selective use of assisted hatching and preimplantation genetic screening for aneuploidy based on the age of the woman. Both these procedures were used as needed by top clinics, not across the board for all patients. No preference for either day 3 or day 5 transfer was obvious among the top clinics.

Laboratory Environment. Best labs took measures to assure good air quality such as positive air pressure in the lab, HEPA filtration of lab air, extra filters to remove volatile organic compounds (think smelly chemicals like organic solvents- tile adhesives, paints, ehtanols) from the air, use of laminar flow hood to keep work surfaces sterile and heated stages to maintain warm temperatures for embryos and gametes when they are being handled outside of the incubator. These are really minimal requirements but surprisingly, these minimal requirements are not consistently found in every IVF lab. I have heard of labs without hard OR ceilings so controlling air flow is not possible. I have walked into labs with no moving air so its like a crypt in the lab. And I have seen labs where surfaces were not properly or consistently warmed.

The Human Factor. Intangibles associated with high success rates are sufficient number of experienced IVF personnel (doctors, nurses and lab technicians).  Members of the IVF team need to have a consistent approach and high attention to detail. Good communication between all members of the team were found essential to keep everyone on track and alert to problems.

So there you have it. Because there is no control group (worst IVF programs?) and because there are some selection criteria applied to inclusion in the study, this paper is not a perfect scientific study. But it does provide an insight into various phases of IVF treatment and what is probably important to achieving high pregnancy rates and low multiple births for patients. I hope that this review gives you some items for comparison among candidate programs when you are shopping for a good program and also some topics to discuss with your doctor.

© 2010 – 2015, Carole. All rights reserved.

12 Responses to this entry

  • webdesign Says:

    my God, i thought you were going to chip in with some decisive insght at the end there, not leave it
    with ‘we leave it to you to decide’.

  • Carole Says:

    I appreciate your comment because I am sure that other readers are frustrated that I don’t simply say, Go to program X, it’s the best. Or this treatment is always superior to that treatment. Sometimes I do state a strong opinion, if it is anchored in scientific fact. For instance, it is a fact that if your tubes are blocked, insemination and intercourse won’t work. On the other hand, it is my opinion that day 5 transfers give better pregnancy results because they did in my program. But in other programs, that may not be the case and the patient is better served to go with the strengths of THEIR program. For much of ART, there is enough variation in effective treatments and enough differences in patient preferences, I would be flat out wrong to impose my opinion on my readers because that won’t always be the right answer for them. My goals are to explain basic biology, explain the scientific basis to ART treatments, give patients tools to find the best infertility treatments for them based on consumer information, not advertising.

  • Ten things about IVF that you must know | Fertility Lab Insider Says:

    […] Common practices of the best IVF programs […]

  • Anonymous Says:

    My BMI is within normal range, but my body fat percentage (measured by my scale and also calculated manually using my body dimensions) is 35% which is considered too high. Could high body fat percentage cause infertility?

  • Anonymous Says:

    Hi Carole,
    Can you elaborate more on the group culturing of the embryos? What other ways do labs do it? Thanks!

  • Carole Says:

    There is a lot of scientific data to suggest that weight extremes in either direction can cause hormonal dysfunction and therefore fertility problems. This is really a medical question for your doctor- not your embryologist! 🙂 Best wishes!

  • Carole Says:

    Some labs culture each embryo in its own microdrop from the beginning to the end. A microdrop is a tiny volume (35 to 50 microliters of medium under a oil layer to help maintain pH and temp for brief periods out of the incubator. Some labs do the fertilization step in a larger volume of medium in a test tube, then move embryos to drops in dishes. Some labs culture a group of eggs with a swarm of sperm and give each normally fertilized egg its own drop later or continue co-culture. I like group culturing because there is evidence that embryos produce growth factors and co-culture may be beneficial to their development. There are lots of ways to grow embryos that will work.

  • Jane Says:

    Regarding culture media, is it lab created, something a vendor supplies, a combo of sorts? What kind of variation is there lab to lab and is there such a thing as a “better culture media” and would explain better results?

  • Carole Says:

    In the old days, every IVF lab made their own medium because there were no commercial vendors. Making good medium is not a trivial matter because it must be made precisely every time and each batch or “lot” must be tested to ensure it is embryo safe. Before commercial vendors took over this process, there was lots of variability in culture media from batch to batch or lab to lab. Labs would have to keep or have access to mouse colonies to create mouse embryos in vitro to test the new medium batches. Embryologists are not pharmacists so this home brew method was not ideal. When commercial vendors came on the scene, it became possible to get high quality medium consistently. That doesn’t mean that from time to time even the big vendors might have manufacturing issues but it’s a whole lot better regulated. My favorite medium was from Vitrolife because their medium was backed up by two decades of animal IVF studies and they had really good scientific support for the IVF labs. I have no commercial stake in Vitrolife but I liked the embryos we got with this medium. So in answer to your question, almost every lab buys their medium these days. Some labs may buy a protein supplement to add to the medium but both the base medium and supplements are produced commercially even if they are combined in the IVF lab just before use. Yes, there is better culture medium. One lab I knew bought research quality medium from an IVF vendor because it was cheaper than the human culture medium. The company was not pleased because the bottles were clearly labeled “For research only”. So some labs may try to cut costs by making their own medium or using medium not intended for human IVF to save money- this is an example of “worse culture medium” and could make a difference.

  • Jane Says:

    “One lab I knew bought research quality medium from an IVF vendor because it was cheaper than the human culture medium. The company was not pleased because the bottles were clearly labeled “For research only”.”

    OMG! If I were a patient there I would ask if they would feed their children “for research only” Milk. That is terrible.

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  • Kirsten Says:

    Wonderful blog – thanks for all of the tips. My RE has high success rates, but it’s also reassuring to see that he generally follows all of the practices you outline above. Thanks for the good feedback!

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