Progesterone is the ovarian steroid produced by the granulosa cells of follicles after the LH peak at mid-cycle. Its role is to sustain embryo endometrial implantation and ongoing pregnancy. Other biological effects of progesterone may exert a protective function in supporting pregnancy up to birth. Luteal phase support (LPS) with progesterone is the standard of care for assisted reproductive technology. Progesterone vaginal administration is currently the most widely used treatment for LPS. Physicians and patients have been reluctant to change an administration route that has proven to be effective. However, some questions remain open, namely the need for LPS in fresh and frozen embryo transfer, the route of administration, the optimal duration of LPS, dosage, and the benefit of combination therapies. The aim of this review is to provide an overview of the uterine and extra-uterine effects of progesterone that may play a role in embryo implantation and pregnancy, and to discuss the advantages of the use of progesterone for LPS in the context of Good Medical Practice.

Summary: The inability to support the growth and development of a mature fetus up to delivery results in significant human suffering. Current available solutions include adoption, surrogacy, and uterus transplantation. However, these options are subject to several ethical, religious, economic, social, and medical concerns. Ectogenesis is the process in which an embryo develops in an artificial uterus from implantation through to the delivery of a live infant. This current narrative review summarizes the state of recent research focused on human ectogenesis. First, a literature search was performed to identify published reports of previous experiments and devices used for embryo implantation in an extracorporeally perfused human uterus. Furthermore, studies fitting that aim were selected and critically evaluated. Results were synthesized, interpreted, and used to design a prospective strategy for future research. Therefore, this study suggests that full ectogenesis might be obtained using a computer-controlled system with extracorporeal blood perfusion provided by a digitally controlled heart–lung–kidney system. From a clinical perspective, patients who will derive significant benefits from this technology are mainly those women diagnosed with anatomical abnormalities of the uterus and those who have undergone previous hysterectomies, numerous abortions, and experienced premature birth. Ectogenesis is the complete development of an embryo in an artificial uterus. It represents the solutions for millions of women suffering from premature deliveries, and the inability to supply growth and development of embryos/fetuses in the womb. In the future, ectogenesis might replace uterine transplantation and surrogacy.

The aim of this systematic review was to identify clinical decision support algorithms (CDSAs) proposed for assisted reproductive technologies (ARTs) and to evaluate their effectiveness in improving ART cycles at every stage vs traditional methods, thereby providing an evidence-based guidance for their use in ART practice. A literature search on PubMed and Embase of articles published between 1 January 2013 and 31 January 2024 was performed to identify relevant articles. Prospective and retrospective studies in English on the use of CDSA for ART were included. Out of 1746 articles screened, 116 met the inclusion criteria. The selected articles were categorized into 3 areas: prognosis and patient counseling, clinical management, and embryo assessment. After screening, 11 CDSAs were identified as potentially valuable for clinical management and laboratory practices. Our findings highlight the potential of automated decision aids to improve in vitro fertilization outcomes. However, the main limitation of this review was the lack of standardization in validation methods across studies. Further validation and clinical trials are needed to establish the effectiveness of these tools in the clinical setting.

Artificial intelligence (AI) has been experiencing rapid growth in recent years, and numerous applications are improving the single-step efficiency of the whole assisted reproductive technology (ART) procedure. In this review, we collected all the algorithms supplying ART and selected those supporting the clinical assistance to the procedure up to the successful attempt. Those with a clear role in improving ART performances were further selected. We found a questionnaire-based algorithm identifying patients at risk for endometriosis with early management and better fertility outcome. An algorithm can detect the values of simple gamete production (male) and reservoir (female) according to gradual scale allocation, and display themas normal or abnormal, spontaneousor stimulated gamete production. This can provide significant benefits for infertile couples undergoing diagnostic and therapeutic journeys. The calculators for the starting dose of gonadotropins and the trigger timing during controlled ovarian stimulation make clinical management more efficient. With the application of AI in ART, the ability to determine the optimal number of metaphase II oocytes required for blastocyst formation and number of oocytes needed for embryo production has been significantly improved. The calculation of the implantation rate as proposed in different calculators, using the ultrasound of endometrial vascularization or the age and euploidy of the embryo transferred, may provide further advancement in managing the ART procedure with more participation from the couples to increase the efficacy of the procedures. Finally, the calculator of presumptive success with an ART program based on couples or medical center profiling and efficiency is of tremendous comfort to couples. In conclusion, algorithms and machine learning development in human reproduction are growing daily with evident benefits. Infertility treatments by in vitro fertilization (IVF) are assisted by several algorithms that improve the efficiency of each procedure step, making IVF program’s management more effortless.

Background: Infertility affects around 17.5% of reproductive-aged individuals worldwide, posing significant personal and public health challenges. Although Medically Assisted Reproduction and Assisted Reproductive Technology (ART; e.g., in vitro fertilization) have advanced outcomes, many couples fail to conceive due to unaddressed pelvic, uterine, or systemic factors. Objectives: We aim to (1) define the current usage of Restorative Reproduction Medicine (RRM) in clinical practice, (2) compare RRM outcomes with conventional ART, and (3) propose an integrated model of RRM plus ART for optimal fertility care. Design: A systematic review following PRISMA guidelines was conducted (INPLASY registration no. INPLASY2024110069). Data sources and methods: We searched PubMed, Scopus, and Web of Science (January 1995–October 2024), combining terms such as “restorative reproductive medicine,” “intrauterine adhesions,” “myomas,” “polyps,” “hydrosalpinx,” “endometritis,” “BMI,” “thyroid dysfunction,” “microbiome,” and “assisted reproductive technology.” Inclusion criteria: studies on uterine/systemic factors affecting infertility, focusing on surgical/pharmacological RRM interventions and ART limitations. Exclusion criteria: male-only infertility, case reports, narrative reviews, non-English publications. Quality assessment employed the Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool. We also briefly noted potential publication bias due to language and study-type restrictions. Results: From >25,000 initial titles, 3 sequential screenings yielded 145 key articles addressing uterine (septum, myomas, polyps, adhesions) and systemic (body mass index (BMI) extremes, thyroid dysfunction, microbiome imbalance) factors. Surgical corrections (e.g., hysteroscopic removal of polyps/myomas, salpingectomy for hydrosalpinx) significantly improved natural conception and ART success (⩾20%–40% increase in clinical pregnancy). Chronic endometritis treatment, endometrial microbiome modulation, and BMI/thyroid optimization further improved pregnancy rates by 15%–20%. Comparisons of RRM versus ART alone indicated that RRM often lowers overall cost and may reduce miscarriage, while ART offers immediate embryo transfer. Combining RRM to correct pathologies prior to ART can boost implantation and live birth rates (⩾40%–70% improvement in some studies). Conclusion: Restorative Reproductive Medicine comprehensively addresses pelvic and systemic abnormalities, thereby enhancing fertility outcomes and complementing ART. A proposed integrated model—RRM diagnostics/interventions followed by ART if needed—maximizes success, reduces time/cost, and emphasizes holistic reproductive health. Further multicenter trials are warranted to standardize protocols and fully realize RRM’s potential in modern fertility care.

Background Recurrent implantation failure (RIF) is a critical barrier in assisted reproductive technology, affecting a significant subset of women undergoing in vitro fertilization (IVF). This systematic review and meta-analysis aimed to systematically review and analyze the causes and treatments of RIF, providing evidence-based insights to enhance clinical management. Methods PubMed, EMBASE and the Cochrane database of systematic reviews were searched for articles published up to February 29, 2024. Studies were selected if they involved human subjects undergoing IVF, reported pregnancy outcomes, and addressed embryonic or extraembryonic factors influencing implantation. A total of 4,380 articles were screened, and 75 studies were included in the meta-analyses. Odds ratios and 95% confidence intervals were pooled using fixed and random effects models, with heterogeneity assessed via I 2 , τ 2 , and Cochran's Q test. Key factors analyzed included embryo euploidy, uterine abnormalities, thyroid function, and chronic endometritis, while treatments evaluated included antibiotics, heparin, platelet-rich plasma, and assisted hatching. Results Meta-analyses revealed that embryo euploidy significantly improves the odds of clinical pregnancy, while untreated hydrosalpinx and chronic endometritis significantly decreases the odds of pregnancy. Effective interventions include antibiotics for chronic endometritis, hysteroscopy for uterine abnormalities, and heparin for specific coagulation disorders. Other treatments, such as platelet-rich plasma and assisted hatching, require further evidence. Conclusions RIF management demands a tailored approach, emphasizing comprehensive diagnostics and personalized interventions. Despite the growing recognition of RIF, inconsistencies in its definition and limited high-quality evidence for certain treatments remain challenging. Further research is essential to standardize protocols and improve outcomes.