Elpiniki Chronopoulou

Introduction: Intrauterine insemination (IUI) is one of the most widespread fertility treatments. However, IUI protocols vary significantly amongst fertility clinics. Various add‐on interventions have been proposed to boost success rates. These are mostly chosen arbitrarily or empirically. The aim of this systematic review and meta‐analysis is to assess the effectiveness and safety of add‐on interventions to the standard IUI protocol and to provide evidence‐based recommendations on techniques used to optimize the clinical outcomes of IUI treatment.Material and Methods: Systematic review and meta‐analyses were performed in accordance with PRISMA guidelines. A computerized literature search was performed from database inception to May 2023. Randomized controlled trials (RCTs) were included reporting on couples/single women undergoing IUI with any protocol for any indication using partner's or donor sperm. A meta‐analysis based on random effects was performed for each outcome and add‐on. Three authors independently assessed the trials for quality and risk of bias and overall certainty of evidence. Uncertainties were resolved through consensus. Primary outcomes were ongoing pregnancy rate (OPR) or live birth rate (LBR) per cycle/per woman randomized. Registration number PROSPERO: CRD42022300857.Results: Sixty‐six RCTs were included in the analysis (16 305 participants across 20 countries). Vaginal progesterone as luteal phase support in stimulated cycles was found to significantly increase LBR/OPR (RR 1.37, 95% CI 1.09–1.72, I² = 4.9%) (moderate/low certainty of the evidence). Endometrial scratch prior/during stimulated IUI cycles may increase LBR/OPR (RR 1.44, 95% CI 1.03–2.01, I² = 1.8%), but evidence is very uncertain. Results from two studies suggest that follicular phase ovarian stimulation increases LBR/OPR (RR 1.39, 95% CI 1.00–1.94, I² = 0%) (low certainty of evidence). No significant difference was seen for the primary outcome for the other studied interventions.Conclusions: The findings of this systematic review and meta‐analysis suggest that vaginal luteal phase progesterone support probably improves LBR/OPR in stimulated IUI treatments. In view of moderate/low certainty of the evidence more research is needed for solid conclusions. Further research is also recommended for the use of endometrial scratch and ovarian stimulation. Future studies should report on results according to subfertility background as it is possible that different add‐ons could benefit specific patient groups.

Background: There is no consensus on tests required to either diagnose unexplained infertility or use for research inclusion criteria. This leads to heterogeneity and bias affecting meta‐analysis and best practice advice.Objectives: This systematic review analyses the variability of inclusion criteria applied to couples with unexplained infertility. We propose standardised criteria for use both in future research studies and clinical diagnosis.Search strategy: CINAHL and MEDLINE online databases were searched up to November 2022 for all published studies recruiting couples with unexplained infertility, available in full text in the English language.Data collection and analysis: Data were collected in an Excel spreadsheet. Results were analysed per category and methodology or reference range.Main results: Of 375 relevant studies, only 258 defined their inclusion criteria. The most commonly applied inclusion criteria were semen analysis, tubal patency and assessment of ovulation in 220 (85%), 232 (90%), 205 (79.5%) respectively. Only 87/220 (39.5%) studies reporting semen analysis used the World Health Organization (WHO) limits. Tubal patency was accepted if bilateral in 145/232 (62.5%) and if unilateral in 24/232 (10.3%). Ovulation was assessed using mid‐luteal serum progesterone in 115/205 (56.1%) and by a history of regular cycles in 87/205 (42.4%). Other criteria, including uterine cavity assessment and hormone profile, were applied in less than 50% of included studies.Conclusions: This review highlights the heterogeneity among studied populations with unexplained infertility. Development and application of internationally accepted criteria will improve the quality of research and future clinical care.

Background: Demystifying the events around early pregnancy is challenging. A wide network of mediators and signaling cascades orchestrate the processes of implantation and trophoblast proliferation. Dysregulation of these pathways could be implicated in early pregnancy loss. There is accumulating evidence around the role of Wnt pathway in implantation and early pregnancy. The purpose of this study was to explore alterations in the expression of Wnt4, Wnt6 and β-catenin in placental tissue obtained from human first trimester euploid miscarriages versus normally developing early pregnancies. Methods: The study group consisted of first trimester miscarriages (early embryonic demises and incomplete miscarriages) and the control group of social terminations of pregnancy (TOPs). The placental mRNA expression of Wnt4, Wnt6 and β-catenin was studied using reverse transcription PCR and real time PCR. Only euploid conceptions were included in the analysis. Results: Wnt4 expression was significantly increased in placental tissue from first trimester miscarriages versus controls (p = 0.003). No significant difference was documented in the expression of Wnt6 (p = 0.286) and β-catenin (p = 0.793). There was a 5.1fold increase in Wnt4 expression for early embryonic demises versus TOPs and a 7.6fold increase for incomplete miscarriages versus TOPs – no significant difference between the two subgroups of miscarriage (p = 0.533). Conclusions: This is, to our knowledge, the first study demonstrating significant alteration of Wnt4 expression in human placental tissue, from failed early pregnancies compared to normal controls. Undoubtedly, a more profound study is needed to confirm these preliminary findings and explore Wnt mediators as potential targets for strategies to predict and prevent miscarriage.

Purpose Women who pursue fertility at an advanced age are increasingly common. Family planning and sexual education have traditionally focused on contraception and prevention of sexually transmitted diseases. A focus should now also be placed on fertility awareness and fertility preservation. This manuscript aims to give an update on the existing evidence around elective oocyte cryopreservation, also highlighting the need for fertility education and evidence-based, individualized counselling. Methods A thorough electronic search was performed from the start of databases to March 2020 aiming to summarize the existing evidence around elective egg freezing, the logic behind its use, patient counselling and education, success rates and risks involved, regulation, cost-effectiveness, current status and future perspectives. Results Clinician-led counselling regarding reproductive aging and fertility preservation is often overlooked. Elective oocyte cryopreservation is not a guarantee of live birth, and the answer regarding cost-effectiveness needs to be individualized. The existing studies on obstetric and perinatal outcomes following the use of egg freezing are, until now, reassuring. Constant monitoring of short-term and long-term outcomes, uniform regulation and evidence-based, individualized counselling is of paramount importance. Conclusions Elective oocyte cryopreservation is one of the most controversial aspects of the world of assisted reproduction, and a lot of questions remain unanswered. However, women today do have this option which was not available in the past. Elective oocyte cryopreservation for age-related fertility decline should be incorporated in women’s reproductive options to ensure informed decisions and reproductive autonomy.

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Vaginal cuff dehiscence (VCD) is a serious complication of total laparoscopic hysterectomy (TLH) or trachelectomy with high morbidity, as it can potentially lead to evisceration/bowel ischemia and sepsis. Authors present a case report of vaginal cuff dehiscence after laparoscopic trachelectomy. The patient reported post-coital onset of symptoms. She presented with acute abdomen and required urgent surgical intervention. In this case surgical management was dictated by the clinical manifestation. However, authors argue that conservative management is also an option for some of these patients and the decision regarding the management plan should be personalized according to the clinical presentation and the patient’s expectations. Emphasis should be given to avoid early onset of sexual activity during the immediate recovery period. Compared to women who underwent an abdominal or vaginal hysterectomy, those who had a laparoscopic procedure have less post-operative pain, shorter recovery period and often they are advised to return early to their normal habits and their work place. It is expected that this group of patients feel well enough to resume sexual activity soon after their procedure. Therefore, our counselling is of paramount importance as it should be highlighted that sexual intercourse is possibly the most common triggering event for VCD which a serious complication with severe morbidity is. The resumption should, therefore, follow medical consultation and be individualized according to co-morbidities which could affect healing, intraoperative findings and evaluation of the whole recovery progress.

Premature luteinization (PL) affects 12.3–46.7% of fresh in vitro fertilization cycles, and there is accumulating evidence confirming its negative effect on success rates. However, despite its clinical significance, PL is poorly understood and defined. This narrative review aims to provide a fresh look at the phenomenon of PL by summarizing the existing evidence and re-evaluating fundamental issues.