Molecular Determinants of Uterine Receptivity: Comparison of Successful Implantation, Recurrent Miscarriage, and Recurrent Implantation Failure.

Embryo implantation is one of the most remarkable phenomena in human reproduction and is not yet fully understood. Proper endometrial function as well as a dynamic interaction between the endometrium itself and the blastocyst-the so-called embryo-maternal dialog-are necessary for successful implantation. Several physiological and molecular processes are involved in the success of implantation. This review describes estrogen, progesterone and their receptors, as well as the role of the cytokines interleukin (IL)-6, IL-8, leukemia inhibitory factor (LIF), IL-11, IL-1, and the glycoprotein glycodelin in successful implantation, in cases of recurrent implantation failure (RIF) and in cases of recurrent pregnancy loss (RPL). Are there differences at the molecular level underlying RIF or RPL? Since implantation has already taken place in the case of RPL, it is conceivable that different molecular biological baseline situations underlie the respective problems.

Assisted Reproductive Techniques and Risk of Congenital Heart Diseases in Children: a Systematic Review and Meta-analysis.

Infertility is a growing phenomenon and leads to an increased use of assisted reproductive techniques (ARTs). In recent years, concerns about the safety of these procedures emerged and ARTs were hypothesized to be a risk factor for developing congenital heart diseases (CHDs) in offspring. Our aim is to investigate the association between ART and CHD, specifying results according to various subtypes of defects. We performed a systematic review and random-effects meta-analysis following the PRISMA guidelines. MEDLINE and Google Scholar were searched from January 2011 to May 2022. Data about incidence of CHD in ART were tabulated and extracted from all the studies included. Twenty-four studies were included. Pooled incidence of CHDs after IVF pregnancies was 3% (95% CI 0.3-0.4; I2 = 99%), decreasing to 1% (95% CI 0.00-0.01; I2 = 93%) for major CHDs only. An increased risk of CHDs, especially minor (i.e., not requiring surgical correction), seems to occur in ART compared with non-ART pregnancies [RR 1.71 (95% CI 1.25-2.34; I2 = 99%)]. For major CHDs, not enough evidence is available to assess the real risk. Moreover, some confounding factors (i.e., maternal age and male infertility) seem to play a critical role to determine an increased risk of CHDs. Conflicting results emerged among the studies, setting the need for further research to validate the actual evidence and state the real risk of CHD following ART pregnancies.

Sexually Transmitted Diseases-An Update and Overview of Current Research.

A rise in the rates of sexually transmitted diseases, both worldwide and in Germany, has been observed especially among persons between the ages of 15 and 24 years. Since many infections are devoid of symptoms or cause few symptoms, the diseases are detected late, may spread unchecked, and be transmitted unwittingly. In the event of persistent infection, the effects depend on the pathogen in question. Manifestations vary widely, ranging from pelvic inflammatory disease, most often caused by Chlamydia trachomatis (in Germany nearly 30% of PID) or Neisseria gonorrhoeae (in Germany <2% of PID), to the development of genital warts or cervical dysplasia in cases of infection with the HP virus. Causal treatment does exist in most cases and should always be administered to the sexual partner(s) as well. An infection during pregnancy calls for an individual treatment approach, depending on the pathogen and the week of pregnancy.

Role of laparoscopic hysterectomy in cervical and endometrial cancer: a narrative review.

Endometrial cancer is the most common carcinoma of the female genital organs and cervical cancer is the leading cause of cancer death in women worldwide. The aim of this review is to evaluate the role of laparoscopic hysterectomy in patients with endometrial and cervical cancer in this period, and analyze the outcome of hysterectomy in terms of survival. Moreover, we present the historical background, new techniques, the anatomical features, and surgical steps of radical hysterectomy. According to new evidence, minimally invasive surgery in patients with cervical cancer is associated with higher rates of recurrence and mortality compared to the open approach. Despite the numerous explanations offered for this phenomenon, the reasons for these results are unclear. Additional large trials have been launched to reevaluate the above-mentioned data. On contrary, the laparoscopic approach provides surgical outcomes and similar survival rates as open surgery in patients with early endometrial carcinoma. Furthermore, the radicality of hysterectomy does not influence local recurrence rates or overall survival in cases with complete surgical removal of the tumor. A laparoscopic radical hysterectomy is no longer an option in patients with cervical cancer. When minimally invasive surgery is offered, the patients must be counseled in detail about the current debate.

Impact of Adenomyosis on Infertile Patients-Therapy Options and Reproductive Outcomes.

Adenomyosis is associated with a negative impact on reproductive outcomes. Although adenomyosis is detected more frequently in women of late reproductive age, its impact on pregnancy rates is important because, in today's world, family planning has shifted towards the late reproductive phase of life for many women. Although the diagnostic indications for imaging studies are well-known, we lack strict diagnostic criteria and classification systems concerning the extent of the disease. Selecting the optimal evidence-based treatment option for adenomyosis is difficult because of the paucity of evidence concerning the association between fertility and the degree and composition of adenomyosis. Furthermore, the treatment of infertility might interfere with the treatment of adenomyosis due to the presence of pain. The aim of this review is to analyze the association between adenomyosis and infertility, and describe treatment options to enhance reproductive outcomes. The following aspects will be addressed in detail: (a) prevalence and causes of adenomyosis, (b) diagnostic tools with imaging techniques, (c) clinical symptoms, (d) proposed pathomechanism of adenomyosis and infertility, and (e) different treatment approaches (pharmacological, surgical, others) and their impact on reproductive outcomes.

Impact of lifestyle and diet on endometriosis: a fresh look to a busy corner.

Endometriosis is a chronic inflammatory disorder with a prevalence of six to ten percent in women of childbearing age. As long as the aetiology of endometriosis is not fully understood and the disease has no definitive treatment, an examination of the environmental factors or interventions that could modify or cure endometriosis would greatly benefit women suffering from this chronic condition. This literature review utilized the electronic databases PubMed, EMBASE, and MEDLINE until February 2021. Studies indicate that fish oil may have a positive effect on reducing endometriosis-related pain due to the effects of pro-inflammatory prostaglandins derived from omega-3 fatty acids. The same effect was seen with the introduction of antioxidant vitamins C, D, and E. There is clinical viability of a low fermentable oligo-, di-, and mono-saccharides and polyols diet to successfully reduce the symptoms of patients who suffer from both endometriosis and irritable bowel syndrome. Despite the low level of evidence, there are frequent associations between endometriosis and gastrointestinal conditions in addition to the influence of various nutritional factors on the disease. The management of endometriosis requires a holistic approach focused on reducing overall inflammation, increasing detoxification, and attenuating troublesome symptoms. A dietician may provide great benefit in the management of these patients, especially at younger ages and in early stages. High-level evidence and well-designed randomized studies are lacking when it comes to studying the effect of lifestyle and dietary intake on endometriosis. Inarguably, further research with a more extensive focus is needed.

Inositols in the ovaries: activities and potential therapeutic applications.

INTRODUCTION: Myo-inositol (MI) and d-chiro-inositol (DCI) play a key role in ovarian physiology, as they are second messengers of insulin and gonadotropins. Ex-vivo and in-vitro experiments demonstrate that both isomers are deeply involved in steroid biosynthesis, and that reduced MI-to-DCI ratios are associated with pathological imbalance of sex hormones. AREAS COVERED: This expert opinion provides an overview of the physiological distribution of MI and DCI in the ovarian tissues, and a thorough insight of their involvement into ovarian steroidogenesis. Insulin resistance and compensatory hyperinsulinemia dramatically reduce the MI-to-DCI ratio in the ovaries, leading to gynecological disorders characterized by hyperandrogenism, altered menstrual cycle and infertility. EXPERT OPINION: Available evidence indicates that MI and DCI have very specific physiological roles and, seemingly, physiological MI-to-DCI ratios in the ovaries are crucial to maintain the correct homeostasis of steroids. Inositol treatments should be evaluated on the patients' specific conditions and needs, as long-term supplementation of high doses of DCI may cause detrimental effects on the ovarian functionality. In addition, the effects of inositol therapy on the different PCOS phenotypes should be further investigated in order to better tailor the supplementation.

Impact of lymphadenectomy on short- and long-term complications in patients with endometrial cancer.

INTRODUCTION: Early endometrial cancer is primarily treated surgically via hysterectomy, adenectomy and, depending on tumor stage and subtype, lymphadenectomy. Systematic lymph node dissection is known to cause surgical complications. The aim of the present study was to investigate morbidity and mortality rates associated with lymphadenectomy in patients with endometrial cancer who underwent surgery in a routine clinical setting. METHODS: We collected data from 232 patients who were operated for endometrial carcinoma between 2006 and 2018 at the University of Lubeck, Germany. Surgical complications were viewed in relation to surgical risk factors. Additionally, a questionnaire concerning long-term lymphatic complications and survival was completed. Survival was compared between patients who underwent lymphadenectomy (group I) and those who did not (group II). RESULTS: Patients in group I needed revision surgery significantly more often due to postoperative complications (such as lymphoceles) compared to those in group II (p = 0.01). The results indicate more serious complications in patients who underwent a systematic lymphadenectomy and in those with lymph node metastases. 15% of patients who underwent a systematic lymphadenectomy had lymph node metastases. Recurrences occurred in 12.5% of cases and were significantly more frequent in patients who had undergone a lymphadenectomy, even if the lymph nodes were negative (p = 0.02). A comparison of survival data during the follow-up period revealed no significant difference. The study highlighted the need for a better preoperative risk stratification and the avoidance of lymphadenectomy for surgical staging alone.

Robotic surgery in gynecology: is the future already here?

Robotic-assisted surgery has gained widespread acceptance in the surgical community and appears to be the most rapidly developing sector of minimally invasive surgery. However, robotic surgery has been viewed as a development of, or alternative to, laparoscopic surgery and not necessarily as a superior technology. The advantages of MIS over open surgery apply to robotic-assisted surgery as well. Nevertheless, conflicting data have been published about the advantages and disadvantages of robotic-assisted and laparoscopic surgery. In the last few years, robotic-assisted surgery has been used for various gynecological procedures such as hysterectomy, lymphadenectomy, myomectomy, sacrocolpopexy or endometriosis operations. In the present review, we analyze the current use of robotic-assisted surgery and its efficiency in gynecology. Patient-based outcomes, such as quality of life and outcomes in morbidly obese patients are also addressed. The potential benefits of single-port robotic-assisted surgery are discussed. Most of the studies published so far state that robotic-assisted surgery does not essentially improve the surgical outcome compared to conventional laparoscopic surgery. However, randomized studies are scarce. Ongoing technological progress over the next few years may improve robotic-assisted techniques and thus optimize the patient's treatment.

Pipelle endometrial sampling success rates in Kazakhstani settings: results from a prospective cohort analysis.

The aim of this study was to evaluate the feasibility of Pipelle endometrial sampling and to explore factors influencing Pipelle success rate in the clinical settings of Kazakhstan. This prospective analysis included 87 patients who had undergone Pipelle biopsy due to medical indications for endometrial sampling. We analysed physician and patient-related factors potentially influencing the success rate of this method. Pipelle endometrial biopsy overall success rate was 82.76%. The indications for the procedure and patients' age were key factors influencing Pipelle sampling success (p < .001). The success rate was the highest in the group with abnormal uterine bleeding as a biopsy indication in the reproductive age group (93.19%; p < .001).Pipelle biopsy was found to be an acceptable option for endometrial sampling in our clinical setting; at the same time, physicians should consider the potential influencing factors on its success rate like indications for the procedure, BMI and patients' age as well as their menopausal status. In order to provide precise future directions, there is a need to study a larger number of patients.IMPACT STATEMENTWhat is already known on this subject? Compared to dilation and curettage sampling conducted in the operation room, Pipelle endometrial sampling is relatively inexpensive, associated with less morbidity, safe, accurate, and can be performed in an office setting.What do the results of this study add? This is the first prospective data analysis about Pipelle endometrial sampling in Kazakhstani population.What are the implications of these findings for clinical practice and/or further research? Enabling the timely diagnosis of current endometrial pathology, Pipelle endometrial sampling approach may have an important impact on healthcare safety and efficiency, and improve overall treatment outcomes and the quality of life of Kazakhstani population if used consistently.

Reproductive outcomes after laparoscopic surgery in infertile women affected by ovarian endometriomas, with or without in vitro fertilisation: results from the SAFE (surgery and ART for endometriomas) trial.

We performed a retrospective cohort study, namely "Surgery and ART for Endometriomas" (SAFE) trial (Clinical Trial ID: NCT03717870), including women who underwent laparoscopic cystectomy for endometrioma before first IVF and compared their reproductive outcomes with the ones of women without endometriosis and with unexplained infertility, tubal factor or male factor infertility. We found that women who underwent previous laparoscopic cystectomy for endometrioma had higher FSH and LH levels between the 2nd and 5th day of the cycle before IVF, required higher doses of gonadotrophins for ovarian stimulation and had a lower number of retrieved oocytes compared with other types of infertility. Nevertheless, pregnancy and delivery rates remain comparable to other causes of infertility. In addition, differences in ovarian stimulation parameters between endometriosis and other types of infertility lost significance with the increase of women's age. These pieces of information can be considered useful to make adequate counselling about reproductive outcomes for infertile women with ovarian endometriomas and allow a proper decision-making approach shared with the patient.IMPACT STATEMENTWhat is already known on this subject? Although endometriomas are common findings in infertile women, whether they should be surgically removed before an in vitro fertilisation (IVF) is a long-lasting debate, and current evidence does not offer a robust background to draw firm recommendations.What do the results of this study add? Women who underwent previous laparoscopic cystectomy for endometrioma need higher doses of gonadotrophins for ovarian stimulation and have a lower number of retrieved oocytes, compared with other types of infertility. Pregnancy and delivery rates remain comparable to other causes of infertility.What are the implications of these findings for clinical practice and/or further research? These pieces of information can help to make adequate counselling about reproductive outcomes for infertile women with ovarian endometriomas and allow a proper decision-making approach shared with the patient.

A randomized, double-blind, placebo-controlled pilot study of the comparative effects of dienogest and the combined oral contraceptive pill in women with endometriosis.

OBJECTIVE: To compare the effects of dienogest and a combined oral contraceptive pill (COCP) after laparoscopic surgery on pain and quality of life in women with severe endometriosis. METHODS: A randomized double-blind pilot study was conducted from March 2018 to March 2020 in women with severe endometriosis confirmed by laparoscopic surgery. A total of 108 patients who had undergone laparoscopic surgery received dienogest, COCP, or placebo daily for 6 months. Primary and secondary outcomes were compared between the three groups. RESULTS: Treatment with dienogest or COCP was associated with improved self-reported pain after 6 months of treatment, as evidenced by significantly lower scores for pelvic pain and dyspareunia compared with placebo (P < 0.05). Significant differences in overall quality of life score were observed over 6 months in the dienogest, COCP, and placebo groups (mean difference 22.00, 23.45, and 6.45 points, respectively; P < 0.001). Post-hoc analysis revealed a significant difference in overall quality of life score between the placebo group and the dienogest (P < 0.001) and COCP groups (P = 0.004). CONCLUSION: Postoperative administration of dienogest or COCP reduced endometriosis-associated pain and improved quality of life in women with severe endometriosis. CLINICAL TRIALS REGISTRATION: https://en.irct.ir/trial/43070.

Lymphadenectomy in endometrial cancer - achieving more with less?

The lymph node status of patients with endometrial cancer is known to be a crucial determinant for the prognosis of the disease. It also provides the indication for further adjuvant treatment. The staging of endometrial cancer by surgery has been a controversial issue for more than 30 years. The significant complication rate after lymphadenectomy and the development of minimally invasive surgery have led to the use of sentinel lymph node (SLN) mapping. In the present review, we present the development of surgical staging procedures in patients with endometrial cancer and summarize the recently expanding body of published literature on the subject. SLN mapping is a safe and accurate technique, especially when indocyanine green is used as a tracer. SLN mapping appears to reduce complication rates as well as costs without affecting the oncologic outcome. Large prospective studies are needed to establish the effects of SLN mapping on the outcome of disease, especially in high-risk patients with endometrial cancer. Furthermore, the need for additional systematic lymphadenectomy prior to adjuvant radio-chemotherapy in patients diagnosed with isolated lymph node metastasis during SLN biopsy must be investigated further. This might pave the way for a new surgical approach in patients with endometrial cancer.

Severe direct and indirect complications of morcellation after hysterectomy or myomectomy.

INTRODUCTION: Despite the significant advantages of morcellation, it may be associated with severe complications. We aimed to determine both direct and indirect complication rates of morcellation at gynecological laparoscopy. MATERIAL AND METHODS: This multicenter retrospective study included patients traced from 2008 to 2017. We identified women who underwent an operation with the use of electromechanical power morcellation (EMM) or vaginal manual morcellation during laparoscopy. Clinical records, intraoperative-postoperative outcomes were reviewed. RESULTS: We analyzed 1795 patients who underwent laparoscopic supracervical hysterectomy (LASH), total hysterectomy (TLH), or myomectomy (45.5%, 14.2%, and 40.3%, respectively). No severe intraoperative complications associated with morcellation or parasitic leiomyoma were observed. Patients with unexpected sarcoma were detected in five cases (0.28%). Four of them were detected after LASH and one after vaginal manual morcellation following TLH, who had an intraabdominal recurrence and died after 18 months. The patients after LASH underwent secondary laparotomy for staging; no histological dissemination of sarcoma was observed, however two had a recurrence. The five-year survival rate was 80%. CONCLUSIONS: There is a small risk of intraoperative complications or unexpected malignancy following morcellation, provided the surgeon adheres to regular surgical standards. In patients with a normal size uterus, TLH could be preferred over LASH to avoid morcellation.

Long-term satisfaction of patients after laparoscopic and robotic-assisted hysterectomy.

INTRODUCTION: Da-Vinci-Xi is the most recent device used in gynecologic robotic surgery. The aim of the present study was to compare the long-term satisfaction of patients who had undergone conventional laparoscopic hysterectomy or robotic assisted laparoscopic hysterectomy using the Da-Vinci-Xi surgical system. METHODS: All hysterectomies performed at the University Hospital of Luebeck from 2018 to 2019 were reviewed. Postoperative outcomes were compared between women who had undergone total hysterectomy with da Vinci Xi (n = 42) or conventional laparoscopy (n = 97). Postoperative outcomes included pain, elimination of complaints after surgery, bladder function, sexual function, satisfaction with the cosmetic outcome, positive experiences after robotic surgery, and satisfaction with the surgeon's preoperative explanation. Obese patients were evaluated separately in a subgroup analysis. RESULTS: Both groups had similar baseline characteristics and complication rates. Preoperative complaints subsided after surgery in a little more than 90% of patients. No significant differences were noted between groups in this regard (p = 0.262), or with reference to postoperative pain after one week (p = 0.866) and one month (p = 0.580), stress incontinence (p = 0.343), sexual function (p = 0.766) and the cosmetic outcome of the abdominal incisions (p = 0.273). The majority of patients who had undergone robotic surgery (96.8%) would be willing to undergo the procedure again if necessary. The subgroup analysis of obese patients revealed no significant differences. CONCLUSION: The Da-Vinci-Xi device did not improve the long-term surgical satisfaction of normal-weight or obese patients who underwent hysterectomy compared with patients who underwent conventional laparoscopy performed by experienced laparoscopic surgeons.

Ectopic pregnancy in noncommunicating horn of unicornuate uterus: 3D-ultrasound and primary laparoscopic management.

Unicornuate uterus with pregnancy in the noncommunicating rudimentary horn is extremely rare. Diagnosis requires awareness, high suspicion index, 3D ultrasound, and MRI. If missed, it can be catastrophic. Treatment varies across literature. We present a case where detection was done by 3D ultrasound and primary laparoscopic surgery done for treatment.

Perioperative considerations in the treatment of endometriosis

Endometriosis is one of the most common benign diseases in women of reproductive age. Nearly all gynecological offices and clinics will contain patients with endometriosis; the frequency and severity of the disease will vary from one setting to another. Adjoining specialties, such as internal medicine, general medicine, surgery, urology, orthopedics, neurology and psychosomatic medicine, will be challenged directly or indirectly by various forms of endometriosis and its sequelae. The disease is characterized by pelvic pain, dysmenorrhea, dyspareunia and sterility. Even now, several years may elapse between the onset of the disease and its diagnosis. The diagnosis of endometriosis is complicated by the diversity of the symptoms. A precise documentation of the patient's medical history and thorough diagnostic procedures are essential to establish a robust diagnosis. This article will discuss the perioperative considerations, diagnosis and treatment of endometriosis.

Absorption, distribution, metabolism and excretion of hyaluronic acid during pregnancy: a matter of molecular weight.

INTRODUCTION: For many years hyaluronic acid (HA) was mainly used for its hydrating properties. However, new applications have recently arisen, considering the biological properties of HA and its molecular weight. Clinical application of low molecular weight HA (LMW-HA) initially was supported by specific absorption data. The identification of high molecular weight HA (HMW-HA) absorption pathways and the knowledge of its physiological role allowed to evaluate its clinical application. Based on the immunomodulatory properties of HMW-HA and its physiological involvement as signaling molecule, pregnancy represents an interesting context of application. AREA COVERED: This expert opinion includes in-vitro, in-vivo, ex-vivo and clinical studies on gestational models. It provides an overview of the physiological and the therapeutic role of HMW-HA in pregnancy starting from its metabolism. Indeed, HMW-HA is widely involved in several physiological processes as implantation, immune response, uterine quiescence and cervical remodeling, and therefore is an essential molecule for a successful pregnancy. EXPERT OPINION: Available evidence suggests that HMW-HA administration can support physiological pregnancy, favoring blastocyst adhesion and development, preventing miscarriage and pre-term birth. For this reason, supplementation in pregnancy should be evaluated.

Surgical outcomes of conventional laparoscopic and robotic-assisted hysterectomy.

INTRODUCTION: The aim of the present study was to compare surgical outcomes of total laparoscopic hysterectomy with those of the robotic approach using the da Vinci Xi system. METHODS: Patients who underwent hysterectomy with da Vinci Xi for early endometrial cancer or benign indications from 2018 to 2019 were selected. The control group consisted of patients who underwent conventional laparoscopy. RESULTS: A total of 300 patients were included in the study. The mean duration of surgery differed significantly (p = 0.025) between those who underwent laparoscopy (125.01 ± 76.168) and robotic-assisted surgery (142.96 ± 82.657 min). Blood loss, median hospital stay, intraoperative and postoperative complications were similar in both groups. No statistical difference was observed in the subgroups with a body mass index of more than 30 kg/m2 or more than 40 kg/m2 concerning the duration of surgery or the surgical outcome. CONCLUSION: The da Vinci Xi did not improve surgical outcomes in patients who underwent hysterectomy by trained laparoscopists and takes more time than conventional laparoscopy when performed in patients of normal weight.