The continuum of ovarian response leading to BIRTH, a real world study of ART in Spain.

BACKGROUND: The first biosimilar of recombinant follicle stimulating hormone (rFSH) launched in Europe was Bemfola® in 2014 following a clinical development programme demonstrating efficacy and safety to the satisfaction of the European Medicines Agency. Since then the increasing use of biosimilar rFSH has provided the opportunity to study both effectiveness across the whole population and the variation of rFSH use during routine clinical care in a real-world setting in Spain. METHODS: This is a real-world study of 1222 women treated in 26 assisted reproduction treatment centres throughout Spain providing experience of the use of a biosimilar recombinant follicle stimulating hormone in four distinct populations. The four populations studied were poor responders, suboptimal responders, normal responders and oocyte donors. The primary endpoint was the total number of oocytes retrieved. Secondary endpoints included number of days of rFSH stimulation, total dose of rFSH administered, number of MII oocytes, number of fertilized oocytes, quality of embryos, number of embryos transferred, implantation rates, clinical pregnancy rates following embryo transfer, number of multiple pregnancies and number of serious adverse reactions, including moderate-to-severe OHSS. RESULTS: Differences were seen across the populations both in the characteristics of the women and ART outcomes suggestive of a continuum of fertility prognosis. In the poor responders, suboptimal responders, normal responders and oocyte donor populations the mean age in years was 39.9 (±SD 3.4), 38.4 (±SD 2.9), 34.4 (±SD 3.3) and 26 (±SD 4.6) respectively and number of oocytes retrieved was 4.1 (±SD 2.7), 8.6 (±SD 6.0), 12.2 (±SD 7.2) and 19.5 (±SD 9.5) respectively. The proportion of embryos graded as best quality was 18.5%, 33.0% and 43.8%, and graded as worst quality was 20.4%, 5.8% and 5.8% for poor responders, suboptimal responders and normal responders respectively. In a similar pattern, for poor responders, suboptimal responders and normal responders the implantation rates were 16.0%, (8/50), 22.4% (49/219), 30.6% (97/317) respectively and clinical pregnancy rates were 23.2% (10/43), 30.4% (59/194) and 37.0% (114/308) respectively. Adverse events were reported in only 7 of 1222 women (0.6%). CONCLUSIONS: Overall the results were consistent with the national ART results reported for Spain, hence this study provides reassurance of the clinical effectiveness of a biosimilar rFSH used in a real world setting. TRIAL REGISTRATION: ClinicalTrials.gov identifier - NCT02941341.

Uterine (CD56+) natural killer cells recruitment: association with decidual reaction rather than embryo implantation.

PROBLEM: Whether decidual leukocyte recruitment and/or increase is primarily hormonally regulated or induced mainly by blastocyst implantation is a matter of debate. Thus, this study investigated the number and distribution of leukocyte populations, with emphasis on natural killer (NK) cells of uterine and peripheral type, within decidual tissue from women with decidualized endometrium both related and unrelated to pregnancy and those with ectopic decidua associated with intrauterine pregnancy, as well as in tubal implantation sites. METHOD OF STUDY: Immunohistochemical characterization of immune cells using antibodies to CD3, CD4, CD8, CD20, CD68, CD16, CD56, CD57, in formalin-fixed, paraffin-embedded tissue, and a quantitative analysis of these subpopulations was conducted in tissue blocks from four groups of patients: (i) 20 women with decidualized endometrium due to progestin therapy (i.e. not associated with gestation) (group Prog-D); (ii) 20 women with intrauterine pregnancy-associated ectopic decidua (seven in the Fallopian tube, five in the ovary, five in the uterine cervix, and three in the omentum) (group Ect-D); (iii) 20 women with spontaneous abortion who had an histologic sample of the decidua at the uterine implantation site (group Uter-D); and (iv) 20 consecutive patients who had had an ectopic tubal pregnancy (group Tub-Preg). Twenty gynecologic specimens with marked inflammatory reaction were used as controls (group Con). RESULTS: CD3+, CD4+, CD8+, CD68+ cells were detected in all tissue samples investigated. In contrast, CD20+ cells were detected in all samples in group Con, but only in 75%, 25%, 55% and 70% of groups Prog-D, Ect-D, Uter-D and Tub-Preg, respectively. In all tissue samples investigated, CD57+ and CD16+ cells were detected. Conversely, CD56+ cells were completely absent in 15 of 40 cases (37.5%) lacking decidual reaction (group Tub-Preg, 7/20; group Con, 8/20) but were present in all cases showing decidual reaction. In contrast with CD56+ cells, CD57+ NK cells were more abundant in group Con than in the four study groups. CONCLUSIONS: CD56+ NK cells are closely related to decidua irrespective of its eutopic or ectopic location rather than to the implantation site. This suggests that the recruitment and/or increase of uterine NK cells into the uterus is not dependent on the physical presence of an implanting embryo but instead is controlled hormonally.

Estudio aleatorizado del dispositivo liberador de levonorgestrel frente a resección endometrial para el tratamiento de la menorragia / Levonorgestrel intrauterine system versus endometrial resection for the treatment of menorrhagia: a randomized study

Objetivo: Tratamiento de la menorragia mediante resección endometrial y dispositivo liberador de levonorgestrel (LNG-IUS). Material y métodos: Estudio aleatorizado; en 25 pacientes se realiza una resección endometrial y en 25 se coloca un LNG-IUS, con un seguimiento a 12 meses. Las variables estudiadas fueron la concentración de hemoglobina, el patrón de sangrado menstrual y el grado de satisfacción. Resultados: En ambos grupos se incrementó la hemoglobina y el patrón de sangrado más frecuente fue el de amenorrea o hipomenorrea. El spotting fue el síntoma adverso más común para el LNG-IUS. El grado de satisfacción fue del 94% en el grupo de resección y el 86% en el de LNG-IUS. Conclusiones: Ambos tratamientos son efectivos para reducir el sangrado menstrual

Objective: To asses the efficacy of endometrial resection and the levonorgestrel intrauterine system (LNG-IUS) in the treatment of menorrhagia. Material and methods: Fifty women were randomized to either insertion of a LNG-IUS or endometrial resection. Hemoglobin levels, menstrual bleeding patterns and degree of satisfaction were evaluated during a 12-month follow-up. Results: Hemoglobin levels increased in both groups. The most frequent bleeding patterns were amenorrhea and hypomenorrhea. The most common adverse effect in the LNG-IUS group was the presence of spotting. Ninety-four percent of the patients in the resection group and 86% of those in the LNG-IUS group were satisfied with the treatment. Conclusions: Both treatments were effective in reducing menstrual blood loss

Efficacy of two regimens of misoprostol for early second-trimester pregnancy termination.

OBJECTIVE: To compare the efficacy of a combined regimen of misoprostol with vaginal misoprostol for early 2nd-trimester pregnancy termination. METHODS: This is a prospective study that includes 79 pregnant women who requested legal termination of 2nd-trimester pregnancy between 13 and 22 weeks. Two regimens of misoprostol were used. Group 1: 400 microg of oral plus 400 microg vaginal misoprostol every 8 h (combined regimen) and group 2: 400 microg of vaginal misoprostol every 3 h up to a maximum of five doses (vaginal regimen). RESULTS: The induction-to-abortion interval was significantly longer in group 1 (25.5 +/- 24.45 h) than in group 2 (15 +/- 7.14 h) (p = 0.016). The abortion rate within 24 h in group 1 was of 56.8 vs. 85.7% in group 2 (p = 0.006). The hazard rate for vaginal delivery within 24 h was found to be 2.277-fold greater in the group with the combined therapy once controlled for plausible confounders. CONCLUSIONS: Our study suggests that oral misoprostol combined with vaginal misoprostol does not reduce the induction-to-abortion interval compared to an exclusively vaginal route when used for early 2nd-trimester pregnancy termination.