OBJECTIVE

To compare the efficacy and safety of the use of transdermal estradiol hemihydrate (Oestrogel) and oral estradiol valerate (Proginova) in cryoprotocols of ART programs in routine clinical practice.

MATERIAL AND METHODS

In the multicenter prospective comparative study were included 260 patients aged 10—40 years planning pregnancy as a result of the cryoprotocol (cryo transfer of embryos) of the ART program in a cycle on hormone replacement (estradiol) therapy using their own genetic material. The recruitment of patients was carried out from March to September 2020 in 16 clinics in Russia providing medical assistance under ART programs. All patients were divided into two groups depending on the prescribed treatment. The doctor’s decision to prescribe a particular drug to the patient (in accordance with the approved instructions for medical use), as well as the tactics of further observation and treatment, was made before the patient was included in the study and independently of it. Patients of the first group (130 women) received therapy of transdermal estradiol hemihydrate (Oestrogel, transdermal gel), patients of the second group (130 women) — oral estradiol valerate (Proginova, pills) from 2—4 days of the menstrual cycle of cryotransfer period. Follow-up of patients in the study continued until confirmation of the onset of biochemical pregnancy (14—15 days after cryotransfer), the frequency of which was considered the primary endpoint of efficacy. The study also assessed the dynamics of endometrial thickness (according to ultrasound investigation), the duration and total dose of the estradiol used, as well as indicators of the blood coagulation system (APTT, antithrombin 3, platelets and fibrinogen) and the concomitant therapy used to correct it, if necessary. Safety was assessed by the total number of adverse events in patients, stratified by severity and frequency. Statistical analysis was performed using the IBM SPSS 23 software.

RESULTS

According to the primary criterion for evaluating the effectiveness (the incidence of biochemical pregnancy), the patients of the study groups did not differ (54.6% and 55.4%, respectively, p=0.901), as well as the dynamics of changes in the thickness of endometrium during treatment — the frequency of achieving the thickness of endometrium in the groups ≥8 mm on the day of cryotransfer was 96.1% and 96.2%, respectively, p=0.990. The duration of estradiol treatment was not significantly different between the groups. The average total dose of the drug used until the endometrial thickness is ≥8 mm/before cryotransfer was: 38.5 mg/62.8 mg estradiol hemihydrate in group 1 and 53.2 mg/87.8 mg estradiol valerate in group 2. In the analysis indicators of the blood coagulation system, statistically significant differences were revealed between the groups on days 10—14 of therapy (on the day of administration of gestagens) according to the following indicators: APTT 30.0 and 32.1 sec (p=0.039), fibrinogen 2.87 and 3.23 g/l (p=0.004) for 1 and 2 groups respectively. Antiplatelet agents were used in the study groups as concomitant therapy in 22.3% and 26.9% (p=0.388), anticoagulants in 9.2% and 11.5% (p=0.542) of cases, respectively. 12 mild AEs were identified with complete resolution during the study without significant differences between groups (p>0.05).

CONCLUSION

The presented study results demonstrate the comparable efficacy of the preparations of transdermal estradiol hemihydrate and oral estradiol valerate. However, the study revealed a difference in the total dosage of estrogen preparations to achieve the required endometrial thickness and by the time of cryotransfer — when using etransdermal estradiol hemihydrate, the dose was significantly lower. Also, when assessing the safety, there were no differences in the total number of adverse events, but in the group of oral estroyegna administration, more significant changes in the blood coagulation system were revealed. The revealed trend requires further detailed study.