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Clinical experience, as well as baseline variables such as age, antral follicle count (AFC), serum anti-Mullerian hormone (AMH), body mass index (BMI), and follicular phase serum FSH level, are used in selecting an appropriate dose in patients presenting for their first treatment cycle for IVF.
Repeated COS does not seem to have any adverse effect on ovarian response to higher doses of artificial gonadotropin. The quality of oocytes collected and their embryological developmental potential is not affected by the number of successive stimulation cycles. However, the effect of multiple COS on the health of the oocyte donor needs to be assessed for future purposes.
Aneuploidy rates are equivalent in unstimulated and stimulated IVF cycles. The prevalence of aneuploidy in natural cycles increased with the age of the female partner in a manner identical to that seen in stimulated IVF cycles. Moreover, sustained implantation rates of euploid blastocysts are equivalent in natural and stimulated IVF cycles.
Thus rates of embryonic aneuploidy are not impacted by follicular stimulation with exogenous gonadotropins.
The association between ART treatment and ovarian cancer is likely influenced by increased detection due to multiple ultrasound scans during ART treatment.
Undergoing ART treatment without the presence of endometriosis is not associated with an increased risk of ovarian cancer, which is reassuring. Whether ART treatment increases the risk of ovarian cancer among women with endometriosis needs further investigation.
There is no evidence of a beneficial effect on live birth rate/ongoing pregnancy rate using estrogen as pre-treatment in GnRH antagonist protocol, compared to no pre-treatment. The evidence regarding the effect of oestradiol pre-treatment on the number of oocytes retrieved is conflicting.
Similarly, Progesterone pretreatment is not recommended.
However, estrogen or progesterone are widely used for scheduling purposes. This is probably acceptable given the data on efficacy and safety.
COCP pre-treatment (12-28 days) is not recommended in the GnRH antagonist protocol because of reduced efficacy.
There is evidence of a lower live birth/ongoing pregnancy rate using 12 up to 28 days of COCP pre-treatment in the GnRH antagonist protocol. Even though the evidence for poor responders is less clear, the GDG recommends against (12-28 days) COCP pre-treatment in GnRH antagonist protocol.
In high responders, co-treatment with letrozole may reduce supraphysiological late follicular phase estradiol levels and the incidence of premature progesterone elevation at the end of the follicular phase, thereby impacting positivity on endometrial receptivity. However, this hasn’t been proven beneficial rather it may produce a harmful effect on the pregnancy outcome.
The use of clomiphene or letrozole may lead to a reduction in the number of gonadotropins required and the incidence of OHSS. However, the use of clomiphene citrate or letrozole may be associated with a significant increase in the incidence of cycle cancellations, as well as reductions in the mean number of oocytes retrieved in both the general IVF population and the poor responders. Larger, high-quality randomized trials are needed to reach a firm conclusion before they are adopted into routine clinical practice.
The use of recombinant LH (rLH) + recombinant FSH (rFSH) for ovarian stimulation is probably not recommended over human menopausal gonadotropin (hMG) in GnRH agonist protocols with regards to safety. HMG and rFSH+LH appear to result in an equal probability of pregnancy in GnRH agonist protocols. However, the risk of OHSS appears to be higher with the use of rFSH+rLH. The recommendation is not applicable to GnRH antagonist cycles.
According to the best available evidence, the addition of rLH to rFSH or the use of combination preparations of rLH and rFSH results in similar live birth rates compared to rFSH alone. For the general population, the addition of rLH to rFSH is probably not recommended, however, it could be applied in specific patient groups such as WHO-I anovulatory patients. Further studies would be necessary to strengthen this conclusion in GnRH antagonist-treated patients.
Physicians may choose the follicle size upon which final oocyte maturation is triggered on a case-to-case basis. LaterhCG administration is associated with the retrieval of more oocytes. However, the decision on the timing of triggering in relation to follicle size is multifactorial, taking into account the size of the growing follicle cohort, the hormonal data on the day of pursued trigger, duration of stimulation, patient burden, financial costs, the experience of previous cycles and organizational factors for the center. Most often, final oocyte maturation is triggered at sizes of several of the leading follicles between 16-22 mm.
Use of r-FSH and high E2 levels at trigger are associated with elevated P levels in the late follicular phase. Fresh embryo transfers performed in spite of elevated P levels are associated with low pregnancy rates and unfavorable outcomes.
Progestins effectively block the LH surge and do not affect the number and quality of collected eggs and obtained embryos. Its main constraint is that it requires total freezing and delayed transfer. With improvements in vitrification, this might be promising. This approach is easy, cheap, and patient-friendly.
Current evidence in normal responders has reported no difference in efficacy in terms of the number of oocytes retrieved with non-conventional start stimulation as compared to conventional start stimulation, however, freeze-all oocytes or embryos is mandatory.
Double stimulation should only be used in the context of clinical research. Due to the absence of RCT, comparing a double stimulation within the same cycle with mandatory postponed transfer and two conventional stimulations, the double stimulation in poor responder patients is not recommended.
However Double stimulation can be considered for urgent fertility preservation cycles.
