The first successful IVF treatment was achieved with a fresh embryo transfer and this continued to be the standard practice for many years. In the first three decades of IVF, embryo freezing was less effective and to ensure the highest chance of achieving pregnancy, multiple fresh embryos were transferred resulting in many multiple pregnancies at the high risk of complications.
Fresh versus frozen embryo transfer in IVF
The advent of freezing techniques and introduction of a technology called vitrification in particular, dramatically increased the success rate of frozen embryo transfers to an extent that a debate ensued in the academic community for several years as to whether fresh embryo transfers should be abandoned in favour of frozen thawed transfers. While there is some place for fresh embryo transfers in select situations, currently frozen embryo transfers comprise the vast majority of embryo transfers worldwide.
Increased effectiveness of vitrification was not the only driver of the switch to frozen embryo transfers, over time it has been realised that high estrogen levels as well as elevated progesterone levels during stimulation of ovaries caused rapid advancement of endometrium, the lining of the womb, leading to asynchrony with embryos and decreased chances of pregnancy with a fresh transfer. This is not rare in stimulated cycles. In such instances it is now possible to synchronise the endometrium with the embryo in a frozen transfer cycle.
Rarely, ovaries can respond excessively to stimulation and ovarian hyperstimulation syndrome can occur. This condition is characterised by fluid collection in the tummy and risk of blood clots. Fortunately, it can be mostly prevented by specific measures during treatment, which includes forfeiting a fresh embryo transfer, since pregnancy hormones also stimulate ovaries and can aggravate the condition. When at risk of hyperstimulation freezing all embryos for later transfer following ovarian quiescence is the safest strategy.
Finally, increasing use of preimplantation genetic testing (PGT) for embryos is also a factor leading to frozen embryo transfers. PGT is a highly accurate technology in identifying embryos that will not implant or reach live birth. As such it allows us to choose the embryos with the highest chance of live birth. Since PGT requires about 10 – 15 days, embryos need to be frozen until results are received. PGT also allows us to screen for particular genetic conditions if the parents are carriers of a genetically inherited condition or affected by them.
Increased success of embryo freezing also improved the cumulative chance of pregnancy from one stimulation cycle through the use of surplus embryos — those remaining after initial transfers. ART Fertility Dubai’s confidence in frozen embryos coupled with a selection of chromosomally normal embryos with PGT allow us to transfer embryos one-by-one in most cases to decrease the risk of multiple pregnancy.
Having a baby after cancer treatment
Additional benefits of vitrification include fertility preservation for medical and elective indications. Over the past four decades, advances in cancer therapies particularly chemotherapeutics, have led to dramatic improvements in patient survival. Given that more patients are surviving their cancer, care is increasingly expanding to include improving long-term health and quality of life. One of the most important quality of life issues in reproductive–age cancer survivors is the ability to have biological children. Freezing of eggs, embryos and ovarian tissue allow female patients the opportunity to preserve their fertility in advance of commencing cytotoxic treatments which may render them infertile. Sperm freezing provides similar opportunities for male patients. ART Fertility Dubai offers fertility preservation services to women and men undergoing treatment for cancer.
There is also a steady increase in the number of women who wish to freeze eggs to prevent age-related infertility. Stable high pregnancy rates with frozen eggs have rendered this a realistic option for over ten years. As such, egg freezing can be regarded as a second revolution after the invention of birth control pills, enabling women control over their reproductive status. Yet, it should be noted that the success of procedures will depend on age at oocyte freezing and the total number of frozen eggs for future use. Indeed, women should not necessarily wait until advanced reproductive age or until their ovarian reserve declines to freeze eggs. The procedure will yield higher chances at younger age and younger women generally produce more eggs in one cycle.
What is the best way to prepare the womb for a frozen embryo transfer?
Frozen embryo transfers can help decrease some other obstetric risks as well. A growing body of evidence to support the association of fresh embryo transfer with increased risk of small-for-gestational-age and low birth weight babies, albeit the absolute risk is still low. On the contrary, frozen embryo transfer in unstimulated cycles decrease the risk of these complications. A meta analysis of 26 studies found that singleton pregnancies achieved after frozen embryo transfer have a reduced risk of preterm birth, small-for-gestational-age and low birth weight babies. However, risk of large-for-gestational-age-babies and hypertensive disorders of pregnancy were found to be higher as compared to pregnancy after fresh embryo transfer. Further research showed that risk of hypertensive disorders was solely related to the absence of ovulation in hormonally prepared frozen embryo transfer cycles — HRT cycles. For this type of preparation, estrogen may be administered orally, vaginally or via the transdermal route. In the majority of HRT protocols estrogens are administered for approximately 2 weeks in an attempt to mimic the natural cycle. Ovaries and uterine lining are monitored by vaginal ultrasound and progesterone administration is usually commenced prior to embryo transfer. Advantages of the HRT protocol include flexibility in the timing of the embryo transfer procedure, less clinic visits for patients and disturbances due to variation in natural cycles can be avoided.
The other alternative is transferring frozen embryos in a natural menstrual cycle without exogenously administered estrogen and progesterone. While capturing the exact time of spontaneous ovulation may require more visits, blood tests, and experience from clinicians, frozen embryo transfer in a natural cycle can yield somewhat higher pregnancy rates and the presence of a ‘corpus luteum’ — hormonally active post-ovulatory follicle that seems protective against pregnancy induced hypertension and postpartum bleeding.
Each patient is different with regard to anatomy and ovulation pattern, underlying risk factors for pregnancy complications, as well as need for scheduling. The importance of collecting a full and detailed medical history at the first consultation including previous treatment cycles and previous pregnancy outcomes cannot be over stated. ART Fertility Dubai assesses these factors and advises its patients accordingly to ensure that the agreed treatment plan is individualised to best meet their needs.
At ART Fertility Clinics, the vast majority of frozen embryo transfer cycles are performed in spontaneous natural ovulatory cycles. In a natural cycle, follicle growth and spontaneous ovulation are crucial for endometrial preparation. Following ovulation the corpus luteum produces estradiol, progesterone and relaxin which promotes vasodilatation and normotension. The key to success of embryo transfer in a natural cycle is the accurate detection of ovulation in order to determine the timing of the embryo transfer accurately.
At ART Fertility Clinic Dubai, one of our main research interests is the optimisation of frozen embryo transfer in natural cycles. Using its proprietary algorithm, ART Fertility detects ovulation with high precision by both ultrasound monitoring of follicular growth and serial monitoring of hormonal levels resulting in the excellent pregnancy rates achieved of 70- 80 per cent per euploid (chromosomally normal as diagnosed with PGT) single embryo transfer.
ART Fertility aims for healthy, full term pregnancies with safe outcomes for both mother and baby. It does not regard its responsibility to be limited with a positive pregnancy test. As in all aspects of medicine, the plan for a frozen embryo transfer must be individualised to give patients the very best chance of treatment success and safe, healthy pregnancies.
As long as couples maintain their motivation and hope, close to 90 per cent patients will eventually fulfil their dreams. As long as there are eggs, sperm and a womb, there is always a chance. Research has shown that live birth rate is over 90 per cent after the transfer of three euploid blastocyst — PGT normal embryos. Since age determines the chance of generating an euploid blastocyst, treatments are more successful at younger ages.
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