All about IVF.
Are you getting ready for IVF?
Are you considering IVF?
Has your doctor mentioned IVF?
This month the world’s first IVF baby turns 41!
One of the most frequent questions I get is about IVF, and frequently I find that many women don’t fully understand what IVF is.
IVF is in vitro fertilization. This means that eggs are taken out of the body and fertilized with sperm in the lab. Embryos are then grown in culture, and can either be transferred or frozen when they get to the blastocyst stage (the normal stage of implantation in which the embryo is approximately 100-200 cells).
There are many different reasons for IVF.
1. Male factor infertility – low sperm count
2. Tubal factor infertility – blocked sperm
3. Anovulation – not regularly ovulating
4. Age related infertility – can screen embryos or aneuploidy
5. Genetic disease – can test for specific genetic mutations
6. Family planning – can save embryos for conception at a later time
7. Unexplained infertility – all testing is normal, but no conception
I break the process down into steps for my patients:
1. Suppression - this can be done birth control pills, an injectable hormone called lupron, estrogen, or an antagonist
2. Stimulation - subcutaneous injectable hormones (FSH and LH, the normal hormones sent out by the pituitary gland to stimulate egg growth, just in very high and titrated doses). Sometimes patients are candidates for a more minimal approach to stimulation utilizing oral medications like clomid or letrozole
3. Egg retrieval - the most invasive part of the process (this is a transvaginal aspiration with a needle and ultrasound guidance while under anesthesia). Complications are rare (<1%) but include infection, bleeding, damage to surrounding structure.sa
4. Fertilization - can be either conventional (sperm and egg in the same dish and fertilization occurs “naturally”) or ICSI - intracytoplasmic sperm injection (where one sperm is selected and injected into each egg). ICSI is indicated for male factor and when genetic testing is being done, and often considered for unexplained infertility
5. Embryo culture - embryos grow out in the lab until the appropriate stage of implantation, called a blastocyst, at day 5-6 (previously culture was only until day 3 but an improvement in culture media has permitted extended culture and this is more rare now).
6. Embryo transfer or freezing - embryos can be transferred, frozen, or biopsied and tested for genetic disorders at this stage
7. If embryos are frozen – then a frozen embryo transfer will happen later (called an FET). For an FET cycle, you will need to time the transfer with your cycle (a natural cycle or modified natural cycle FET), or you can have a controlled cycle with estrogen priming (most common). Pros and Cons to both and this should be discussed with your RE!
Some game changers for those of us in the field are an improved freezing process (called vitrification, allowing for an increase in frozen embryo transfer cycles and greater focus on the uterine lining) and blastocyst biopsy with preimplantation genetic testing (PGT).
Vitrification is an improved freezing process over the prior “slow freeze” process. Embryo survival rates with vitrification are much better than in years past and we expect 98-99% of embryos to survive the freeze-thaw process. This improvement in technology has allowed us to safely freeze embryos and transfer fewer embryos at a time (typically one).
PGT allows us to test for both aneuploidy (an abnormal chromosome number, which is more common as women age and the most frequent cause of miscarriage) and for single gene disorders (such as cystic fibrosis, spinal muscular atrophy, etc). For PGT embryos are biopsied at the 5-6 day stage (blastocyst). The biopsy is taken from the trophectoderm (the outer cells, or the placental component of the embryo) and not from the actually inner cell mass. This biopsy is then evaluated to see if there is a normal number of chromosomes. Chromosome abnormalities are the most common reason why older women see a decrease in fertility and an increase in miscarriage.
In fact, the percentage of abnormal embryos increase dramatically with age.
In a study evaluating patients undergoing IVF, the percentage of abnormal embryos based on age (Simon Fertil Sterlil 2018);
· AGE <35: 27%
· AGE 35-37: 38%
· AGE 38-40: 55%
· AGE 41+: 72%
Chance of a live birth decreases proportionally, with the most recent SART data (2015) showing the chance of live birth based on age:
· AGE <35: 53%
· AGE 35-37: 40%
· AGE 38-40: 26%
· AGE 41-42: 12%
· AGE >42: 4%
However, with PGT we can significantly improve these live birth rates by transfer of a single euploid embryo to 60-70%. This means that PGT testing is very helpful as women age, but also become more costly as many older women will need multiple cycles to get a normal embryo due to a decrease in ovarian reserve seen with ago.
An honest discussion with your doctor of expectations is very important. Not every egg with be mature, not every mature egg will fertilize, not every fertilized egg will grow in culture to a blastocyst, not every blastocyst is genetically normal, and not every genetically normal embryo becomes a baby. There is loss along the way and setting appropriate expectation is helpful. That said, remember that odds are just guidelines – few don’t really know how your eggs, sperm, embryos will perform in the lab until we try.
Most women are surprised that the active portion of the IVF process is rather quick (approximately 2 weeks from start of hormone injection to the egg retrieval) although there is a lot of passive waiting time (getting the cycle started, time on birth control for suppression, time waiting for an embryo transfer).
The art of this medicine (over the science) is in picking the right protocol for the right patient and monitoring for when the greatest number of mature eggs are present. The science and the always changing tech in the lab is fascinating.
A note about unexplained infertility, it is a very hard diagnosis. If you have been trying to conceive over 1 year, with normal testing, your rate of conception per month decreases after 1 year of trying to 5%, and if over 2 year it drops to 2-3%. This is even more pronounced as women are older.
A few studies to help guide us for treatment in women with unexplained infertility:
The FASTT Trial looked at women unexplained infertility who were divided into 3 groups: Clomid with an IUI, Injectable FSH with an IUI, and immediately to IVF. Pregnancy rates were:
• Clomid + IUI: 7.6%
• FSH + IUI: 9.8%
• IVF: 30.7%
Take home: there was no significant benefit of FSH/IUI, move faster to IVF if not pregnant after clomid + IUI.
The FORT-T Trial included women with unexplained infertility for 6 months when female partner age 38-42. This study looked at 2 cycles of IUI (clomid or FSH) and then IVF or immediately to IVF. Pregnancy rates were:
• Clomid + IUI: 21.6% (after 2 cycles)
• FSH + IUI: 17.3% (after 2 cycles)
• IVF: 49% (1 cycle)
Take home: superior pregnancy rates and fewer cycles with immediate IVF if female partner 38 or older.
These studies help us know that in coupes with “unexplained infertility” – many of the issues that we are not able to diagnose are overcome in the lab but not in an IUI cycle. Factors including fertilization issues, embryo transit, tubal environment, and more may play a bigger role in natural cycles and IUI cycles but are overcome in the controlled and non-toxic environment of the IVF lab. I often have patients with unexplained infertility say “nothing is wrong with me so why do I need IVF? So a reminder: just because none of the tests that are easy for us to do show any issues, does not mean that there is some underlying problem that is just harder to detect yet significantly improved with our most advanced technology: IVF.
For more information, feel free to listen to the podcast epidoes:
IVF