The Fischer protocol for assisted reproductive technology treatment: Real-world data experience comparing elective single versus double embryo transfer with or without comprehensive chromosome screening.

High rates of multiple implantation after assisted reproductive technology (ART) treatment represent one of the major problems for both mothers and their fetuses. Given the availability of techniques intended to identify embryos with the highest chance for development to term, such as comprehensive chromosome screening (CCS) and blastocyst transfer, the decision on the number of embryos to transfer deserves careful consideration. This report presents real-life data from two clinics using the Fischer protocol for cycle programming in patients undergoing ART. Our data indicate that ovarian stimulation using the Fischer protocol provides consistent and optimal ART outcomes in centers following strict quality management standards. However, high multiple implantation rates were observed in fresh and frozen transfer cycles after transferring two embryos - even in patients aged over 39 years. The live birth rates after CCS were superior to those using untested embryos. These findings were held for the three age groups irrespective of the CCS culture day (D1 = PN stages, or D5 = blastocysts). Our results support a single embryo transfer policy, particularly in women under 34 years of age with favorable conditions during ART treatment, i.e., a high number of available fertilized oocytes.

A quality management approach to controlled ovarian stimulation in assisted reproductive technology: the "Fischer protocol".

BACKGROUND: Ovarian stimulation (OS) is crucial for pregnancy success in assisted reproductive technology (ART) treatments. The possibility of programming the OS cycle and oocyte pick-up (OPU) is advantageous to Fertility Centers operating under quality management systems (QMS) as it might increase efficiency and safety. Moreover, cycle programming is patient-centered as it might help IVF patients to most optimally manage domestic and work commitments. In this study, we describe the so-called "Fischer protocol" to IVF cycle programming and present the clinical results of using this approach in two independent Fertility Centers certified according to DIN EN ISO 9001 standards. METHODS: Cycle programming was achieved in normo-ovulatory women with pretreatment administration of norethisterone acetate, followed by OS using individualized doses of recombinant human FSH and recombinant human LH in a fixed 2:1 ratio in association with a flexible GnRH antagonist regimen. The final oocyte maturation was attained with use of GnRH agonist trigger. The oocyte pick-ups (OPU) were scheduled approximately 40 days ahead of the programed OPU date. The cycle outcomes of 647 patients treated using the "Fischer protocol" in the Center where the method was developed (study center 1) are presented. The model was then tested at an independent Fertility Center (study center 2), and the first clinical results using the Fischer protocol in 216 patients are presented and compared with that of 516 patients undergoing conventional OS without cycle programming. RESULTS: The duration of ovarian stimulation was 9±1 day in all treated patients. No OPU was scheduled during weekends or had to be re-scheduled due to issues related to cycle programming. In the study center 1, the highest and lowest mean number of oocytes retrieved was 11.7 (95% confidence interval [CI]: 4.5-22.1) in patients of ≤30 years and 7.7 (95% CI: 1-19) in those aged 40 years and over. No cases of OHSS were recorded in this series. The mean number of embryos transferred was 1.5 and the overall clinical pregnancy rates (CPR) and live birth rates (LBR) were 52.7% and 43.5%, respectively. In the study center 2, patients treated using the Fisher protocol achieved statistically higher oocyte output rate (94.6% vs. 85.0%), number of oocytes retrieved (9.8±7.7 vs. 7.9±7.2), and blastulation rates (55.1% vs. 49.4%) than those treated using conventional OS. The CPR (50.6% vs. 41.1%) and LBR (44.7% vs. 33.2%) also favored the group of patients subjected to cycle programming using the Fisher protocol, although this data mainly resulted from the increased frequency of patients subjected to preimplantation genetic testing for aneuploidy (PGT-A). CONCLUSIONS: An optimal distribution of both clinical and laboratory workload was achieved by using the Fischer protocol. Moreover, oocyte pick-ups were eliminated on weekends and holidays without jeopardizing the quality of care provided to couples. The Fischer protocol is consistent with the quality management philosophy and focusses on improving the quality of care by increasing safety, efficacy, and patient-centeredness without harming treatment effectiveness.

Efficacy of misoprostol before diagnostic hysteroscopy in postmenopausal women: a randomized clinical trial.

OBJECTIVE: To evaluate pain and determine the efficacy of misoprostol, compared with placebo, for postmenopausal women before diagnostic hysteroscopy. METHODS: This randomized, double-blind, placebo-controlled clinical trial included 158 postmenopausal women who received either 200 µg of misoprostol or placebo through the vaginal route before diagnostic hysteroscopy (79 women/group). The primary outcome was pain assessment (presence and intensity) during the four steps of hysteroscopy: cervical grasping with a Pozzi tenaculum forceps immediately before hysteroscopy, during hysteroscopy, during performance of the endometrial biopsy, and postprocedure. The secondary outcomes were duration of the procedure, need for additional cervical dilatation, complications, and adverse effects. RESULTS: Mean ages of the women were 62 ±â€Š8.2 years and 60 ±â€Š7.3 years in the misoprostol and placebo groups, respectively. Abnormal bleeding (misoprostol group, 45.6%; placebo, 43%) and endometrial thickening (54.4% in the misoprostol group and 57% in the placebo group) were the most common indications for the examination in both groups (P = 0.49). There was no significant difference between groups in the pain intensity of the four steps of the procedure. The duration of hysteroscopy was similar in both groups (misoprostol group, 2.5 ±â€Š2.7 minutes; placebo, 2.1 ±â€Š1.6 minutes; P = 0.43). Additional cervical dilatation was needed in 11 women in the misoprostol group versus 9 in the placebo group (P = 0.63). In both groups, there was no significant difference in terms of complications. Adverse effects were reported by 25.3% of women using misoprostol (vaginal bleeding, 11.3%; cramping, 12.6%; diarrhea, 2.5%; 1 woman reported both vaginal bleeding and cramping). In the placebo group, only 2.5% of women developed adverse effects (P < 0.0001). CONCLUSION: Misoprostol does not reduce pain intensity, the duration of the procedure, or need for additional cervical dilatation, and causes more adverse effects when used in postmenopausal women before diagnostic hysteroscopy.

Insights into the role of cervical mucus and vaginal pH in unexplained infertility / Sobre o papel do muco cervical e do PH vaginal na gênese da infertilidade inexplicada

Unexplained infertility diagnosis is made in the presence of a normal semen analysis when tubal patency and normal ovulatory function are established. Among several potential causes, unexplained infertility could be attributed to vaginal pH and cervical mucus abnormalities. Although the vaginal canal and the cervix generally function as effective barriers to sperm, and although the production of mucus is essential to transport them from the vagina to the uterine cavity, these factors receive little attention in the investigation of couples with unexplained infertility. A substantial reduction in sperm number occurs as they transverse the cervix. From an average of 200 to 300 million sperm deposited in the vagina, only a few hundred achieve proximity to the oocyte. Given this expected high spermatozoa loss, a slight modification in cervical mucus may rapidly transform the cervix into a "hostile" environment, which, together with changes in vaginal environment and cervix structure, may prevent natural conception and be a cause of infertility. In this review, we discuss the physiological role of the vaginal pH and cervical mucus in fertility, and describe several conditions that can render the cervical mucus hostile to sperm and therefore be implicated in the pathophysiology of unexplained infertility.

RESUMO O diagnóstico de infertilidade inexplicada baseia-se na presença de espermograma normal, constatadas também permeabilidade tubária e função ovulatória normais. Entre as várias causas potenciais de infertilidade inexplicada, a presença de muco cervical e pH vaginal anormais devem ser consideradas. Embora a produção adequada de muco cervical seja essencial para o transporte dos espermatozóides da vagina para a cavidade uterina, e tanto o canal vaginal quanto o colo do útero desempenham função importante como barreira à passagem dos espermatozóides, estes fatores recebem pouca atenção na investigação de casais com infertilidade inexplicada. Uma redução substancial do número de espermatozoides ocorre à medida que estes percorrem o trato reprodutivo feminino. Partindo de cerca de 200 a 300 milhões de espermatozoides depositados na vagina, apenas algumas centenas alcançam a proximidade do oócito. Alteracões do muco cervical podem rapidamente transformar o colo do útero num ambiente hostil, que em conjunto com alterações no ambiente vaginal e da estrutura de colo do útero, podem apresentar-se condicões impedientes para a concepção natural; desse modo, convertem-se em causa de infertilidade. Nesta revisão, discutimos o papel fisiológico do pH vaginal e do muco cervical na fertilidade, descrever várias condicões que podem tornar o muco cervical hostil aos espermatozoides e, por fim analisamos como estes fatores interferem na fisiopatologia da infertilidade inexplicada.