Progesterone supplementation in natural cycles improves live birth rates after embryo transfer of frozen-thawed embryos-a randomized controlled trial.

STUDY QUESTION: Does supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles improve the live birth rate? SUMMARY ANSWER: Supplementation with vaginal tablets of progesterone after frozen-thawed embryo transfer in natural cycles significantly improves the number of live births. WHAT IS KNOWN ALREADY: Progesterone supplementation during luteal phase and early pregnancy may improve the number of live births after frozen-thawed embryo transfer. However, due to the limited number of previous studies, being mainly retrospective, evidence is still limited. STUDY DESIGN, SIZE, DURATION: This is a prospective randomized controlled trial, performed at two university clinics. In total, 500 subjects were randomized with a 1:1 allocation into two groups, during the period February 2013 to March 2018. Randomization was performed after a frozen embryo transfer in a natural cycle by use of opaque sealed envelopes. The primary outcome was live birth rate; secondary outcomes were pregnancy, biochemical pregnancy, clinical pregnancy and miscarriage rate, and if there was a possible association between the serum progesterone concentration on the day of embryo transfer and live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women, receiving embryo transfer in natural cycles participated in the study. The embryos were frozen on Day 2, 3, 5 or 6. In total, 672 women having regular menstrual cycles were invited to participate in the study; of those, 500 agreed to participate and 488 were finally included in the study. Half of the study subjects received progesterone supplementation with progesterone vaginal tablets, 100 mg twice daily, starting from the day of embryo transfer. The other half of the subjects were not given any treatment. Blood samples for serum progesterone measurements were collected from all subjects on the day of embryo transfer. MAIN RESULTS AND THE ROLE OF CHANCE: There were no differences in background characteristics between the study groups. In the progesterone supplemented group, 83 of 243 patients (34.2%) had a live birth, compared to 59 of 245 patients (24.1%) in the control group (odds ratio 1.635, 95% CI 1.102-2.428, P = 0.017*). The number of pregnancies was 104 of 243 (42.8%) and 83 of 245 (33.9%), respectively (odds ratio 1.465, 95% CI 1.012-2.108, P = 0.049*) and the number of clinical pregnancies was 91 of 243 (37.4%) and 70 of 245 (28.6%), respectively (odds ratio 1.497, 95% CI 1.024-2.188, P = 0.043*). There were no significant differences in biochemical pregnancy rate or miscarriage rate. There was no correlation between outcome and serum progesterone concentration. LIMITATIONS, REASONS FOR CAUTION: The study was not blinded because placebo tablets were not available. Supplementation started on embryo transfer day, regardless of the age of the embryos, which resulted in a shorter supplementation time for Day 5/6 embryos compared to Day 2/3 embryos. WIDER IMPLICATIONS OF THE FINDINGS: Supplementation with progesterone in natural cycles improved the number of live births after frozen-thawed embryo transfer and should therefore be considered for introduction in clinical routine. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by Uppsala University, the Uppsala-Family Planning Foundation, and Ferring Pharmaceuticals AB, Malmö, Sweden. The authors have no personal conflicting interests to declare. TRIAL REGISTRATION NUMBER: NL4152. TRIAL REGISTRATION DATE: 5 December 2013. DATE OF FIRST PATIENT'S ENROLMENT: 18 February 2013.

Carotenoid and protein supplementation have differential effects on pheasant ornamentation and immunity.

A currently popular hypothesis states that the expression of carotenoid-dependent sexual ornaments and immune function may be correlated because both traits are positively affected by carotenoids. However, such a correlation may arise for another reason: it is well known that immune function is dependent on nutritional condition. A recent study has suggested that the expression of ornaments may too depend on nutritional condition, as males in good nutritional condition are better at assimilating and/or modulating carotenoids. Thus, carotenoid-dependent ornaments and immune function may be correlated because both are dependent on nutritional condition. To elucidate if, and how, ornamentation and immune function are linked, pheasant diets were supplemented with carotenoid and/or protein in a fully factorial experiment. Carotenoid treatment affected wattle coloration and tail growth, but not cellular or humoral immunity. Immunity was unrelated to males' initial ornamentation including wattle colour. Males in better body condition, measured as residual mass, increased their wattle coloration more when carotenoid supplemented. Protein positively affected humoral but not cellular immunity, but had no effect on ornaments. Cellular, but not humoral, immunity increased with male body condition. Thus, there was no evidence that an immune-stimulatory effect of carotenoids resulted in wattle coloration honestly signalling immune function, but wattle coloration may still signal male body condition.