Top 14 Risks Associated with IVF: What are they?
In Vitro Fertilization is the most common technique used for resolving complex and challenging infertility cases. It has higher success rates compared to the other Assisted Reproduction Techniques. But it is not always possible to get a positive result. And sometimes IVF may lead to undesired complications starting from empty follicle syndrome, failed fertilization, embryonic arrest, and delayed Embryo Transfer, and ending with Ovarian Hyperstimulation, Miscarriage, ectopic pregnancy, having a preemie newborn, and even surgical complications.
Over the last 5 years, the possible side effect associated with IVF decreased dramatically, and most of them are possible to avoid using the new IVF Protocols and personalizing each stage of the Treatment to the patient’s case.
What are the potential IVF complications?
Poor ovarian response to stimulation & low number of oocytes produced during the cycle
In some cases, the Ovarian Stimulation Protocol could be not as effective as expected. In such cases DuoStimulation Protocol involving two stimulations and two Oocyte Collections are performed during a single menstrual cycle (approximately 24–28 days) can be suggested. But not always even DuoStimulation Protocol can make the ovaries produce an optimal number of oocytes, and if fertilization of a few oocytes is failed, the Embryo Transfer can be cancelled.
Empty follicle syndrome or oocyte maturation arrest
Naturally, once the ovarian follicle has reached an adequate size (17–20 mm), Luteinizing Hormone (LH) is released from the pituitary gland to complete the oocyte maturation and trigger ovulation (the release of the egg from the follicle in the ovary into the fallopian tube). In contrast to natural ovulation, in ART cycles, an hCG (Chorionic Gonadotropin hormone) is used to perform this function.
Despite there are new Ovarian Stimulation Protocols, including DuoStimulation for producing more oocytes in a single cycle, and Dual trigger Protocols that can increase the number and maturity of the oocytes retrieved, Empty Follicle Syndrome (no eggs collected during Egg Retrieval) or oocyte maturation arrest (the oocytes produced by the ovaries are immature) may happen.
In the first case, the fertilization Protocol is canceled as there are no oocytes at all. And in the second case, In Vitro Maturation (IVM) Protocol can be fueled and if Oocyte Maturation would be successful, conventional fertilization or ICSI (Intracytoplasmic Sperm Injection) will be done with following culturing of the embryos and Embryo Transfer.
Ovarian Hyperstimulation Syndrome
Depending on the type of stimulation Protocol used and the ovarian response to stimulation, one of the potential side effects of IVF Treatment is Ovarian Hyperstimulation Syndrome (OHSS). It is a potentially life–threatening complication caused by an excessive response by the ovaries to ovarian stimulation using hormones during IVF/ICSI Treatment. It can be mild, moderate, or severe. Whilst mild to moderate form can be managed without hospitalization, the severe form of OHSS usually requires long Treatment at the hospital.
In the past, cases of OHSS were frequent, but nowadays, Ovarian Hyperstimulation Syndrome is an exception as new Ovarian Stimulation Protocols make it possible to avoid OHSS in 99% of cases.
Possible complications during & after Egg Retrieval
Follicular aspiration’s possible risks include pain, hemorrhages, injuries to the uterine lining, infection in the ovaries and pelvis, injury to the ovaries, uterus, bowel, bladder, or major blood vessels. Nowadays most fertility clinics use the new Oocyte Retrieval needles designed in a way to reduce the possibility of bleeding and the risk of injuries to the uterine lining, whilst minimizing stress in the oocyte during aspiration. And since follicular aspiration is done under ultrasound guidance, the Oocyte Retrieval needle is visualized on the screen which lowers the chance of series problems dramatically: in under 1 in 500 cases.
Fertilization failure
Total Fertilization Failure (TFF) may occur both in convenient fertilization and more sophisticated fertilization technique called ICSI, leading to cycle cancellation. Total fertilization failure may happen if the quality of oocytes is low, if the oocytes are immature, if there is no availability of motile sperm, and/or if sperm has severe defects. Fertilizing the oocytes with abnormal or immature sperm may lead to TFF too. And using the ICSI technique instead of conventional fertilization can also fail.
Embryonic arrest
Fertilization (the fusion of the oocyte and sperm gametes), activates the oocyte to commence embryonic development. And commonly, the embryos from the same cohort (from the same Ovarian Stimulation cycle) develop in different ways: some may develop fast, some — slower, and some might stop their development before they reach the blastocyst stage.
For the first 12 hours after fertilization, the fertilized oocyte remains a single cell. But within 24 hours of being fertilized, it starts dividing fast into many cells. Reaching the blastocyst stage on Day 3, an embryo has up to 10 cells (6–10 cells). On Day 4 it has between 12–50 cells. On Day 5 embryo is called the Blastocyst and it has up to 100 cells.
An embryonic arrest may happen at any stage of the development starting from post–fertilization and up to the blastocyst stage. If there is no cellular division for at least 24 hours that seems an embryo stopped its development. Stopping to develop means an embryonic arrest. Mostly it happens because of gene variations, and chromosomal abnormalities including multiple chromosomal abnormalities, non–activation of embryonic genome, metabolic profile, and morphological features.
Reduced number of top–quality embryos
Embryos generated during IVF may have also different quality. Some of them may feature top quality and high implantation potency, some may be good quality and good implantation potency, and some may be low quality and poor implantation prognosis. And this is why the number of top–quality embryos suitable for transfer can be reduced.
Before doing a Transfer, the Embryologist will evaluate each IVF embryo from the cohort and exclude the ones with low quality and low implantation potency as transferring an embryo with poor implantation prognosis in 90% of cases leads to a negative result.
Cancelled Embryo Transfer
For different reasons, the IVF cycle can be completed without Embryo Transfer. In case of low ovarian response to stimulation, or if there are no oocytes retrieved, the oocytes or/and sperm are immature, the oocytes or/and sperm are abnormal, the endometrium is not thick enough for making embryo implantation possible, if there is a high risk for Ovarian Hyperstimulation Syndrome after triggering final oocyte maturation with hCG injection (Trigger shot), no viable embryos for transfer, Preimplantation Genetic Testing (PGT) is performed and embryos should be vitrified while waiting for the results, or if there is no top quality embryo(s) suitable for transfer, or if there are chromosomal/genetic abnormalities, or if embryos are mosaic, and so on. Some IVF cycles may bring negative results as they do not work. In these cases, a great option to continue your cycle is having a cohort of vitrified oocytes and cryopreserved sperm samples. Alternatively, having a frozen embryo left from the previous cycle as a back–up.
Delayed Embryo Transfer
If there is a high risk of developing Ovarian Hyperstimulation Syndrome (OHSS), Ovarian Torsion, or other complications, the Embryo Transfer can be delayed and all embryos that meet quality criteria will be vitrified and stored until the time when the cycle can be continued. The new cycle will be done without stimulation and Egg Retrieval if using the vitrified embryo (FET).
Embryo Transfer can be delayed also in case of high ovarian response to Ovarian Stimulation followed by the generation of a large number of oocytes. In this situation, after follicular aspiration, the patient is suggested to delay the Embryo Transfer because there is a risk of having a severe complication if pregnancy is achieved.
Not all IVF embryos left after the transfer can be vitrified
Vitrification–Devitrification process is challenging and stressful for the embryos, therefore, not all of them can be cryopreserved for future cycles. If vitrifying the embryos with morphological, chromosomal or genetic abnormalities, or mosaic ones, it would lead to undesirable results, first of all, because such embryos cannot be transferred.
Before deciding on performing or cancelling Embryo Vitrification, each embryo from the cohort undergoes evaluation and selection. Embryo Selection is based on morphological grading and kinetic parameters, which improve the accurate selection of viable embryos suitable for Vitrification. Those embryos that don’t meet selection criteria, won’t be vitrified.
Implantation failure & Miscarriage
Embryo implantation is a biological mystery. The blastocyst comes into contact with the endometrium and forms the placenta that will provide an interface between the growing fetus and the mother. Although embryo quality is essential for implantation, thick and receptive endometrium is also a vital thing for making it possible. If something is wrong, the embryo would not implant.
Implantation failure after IVF happens if the embryo is not good enough (genetically or morphologically abnormal, or mosaic), or the endometrium is not ‘receptive’ enough (doesn’t allow the embryo to implant).
Negative pregnancy test
A pregnancy test measures human Chorionic Gonadotropin (hCG) hormone levels. Increased hCG levels indicate pregnancy. Both urine and blood tests for hCG can be used for this purpose. High levels of hCG detected in urine and blood samples confirm a pregnancy. And vice versa: low levels of hCG confirm that person is not pregnant.
No heartbeat detected on high-resolution ultrasound after positive pregnancy test
Along with confirming a pregnancy, a quantitative hCG test may also indicate abnormal pregnancy and other health conditions not related to pregnancy that can raise hCG levels. So, if the heartbeat is not detected after getting a positive β–hCG, it may seem there is an implantation failure, ectopic pregnancy, or other health conditions.
Multiple pregnancy
Transferring more than one embryo may potentially lead to multiple pregnancy. Multiple pregnancy is a high–risk pregnancy both for mother and fetus.
Currently, in many countries, the number of embryos transferred for completing the cycle is limited to 3 maximum. Most countries transfer two embryos. And in some countries, only one embryo can be transferred per cycle.