The role of minimally invasive surgery in gynaecological cancer: an overview of current trends.

Background: The capabilities of minimally invasive surgery, either as conventional laparoscopy, or as robotic surgery, have increased to an extent that it enables complex operations in the field of gynaecological oncology. Objective: To document the role of minimally invasive gynaecological surgery in cancer. Materials and methods: A review of the literature that shaped international guidelines and clinical practice. Main outcome measures: Current guidelines of major international scientific associations and trends in accepted clinical practice. Results: In recent years, evidence on oncologic outcome has limited the role of minimally invasive techniques in cervical cancer, while the treatment of early endometrial cancer with laparoscopy and robotic surgery has become the international standard. In ovarian cancer, the role of minimally invasive surgery is still limited. Current evidence on perioperative morbidity underlines the necessity to implicate minimally invasive techniques whenever possible. Conclusion: The optimal surgical route for the treatment of gynaecological cancer remains in many cases controversial. The role of minimally invasive surgery remains increasing in the course of time. What is new?: This comprehensive review offers an entire perspective on the current role of minimally invasive surgery in gynaecological cancer therapy.

The LADY study: epidemiological characteristics of prevalent and new genitourinary syndrome of menopause cases in Greece.

OBJECTIVE: The genitourinary syndrome of menopause (GSM) is often underdiagnosed and undertreated despite its significant impact on postmenopausal quality of life. We assessed the prevalence of GSM and associated symptoms in Greek perimenopausal/postmenopausal women attending gynecology clinics. METHODS: Four hundred and fifty women, aged 40-70 years (93.1% postmenopausal), attending three gynecology clinics at university hospitals completed a validated questionnaire and underwent pelvic examination. RESULTS: GSM was diagnosed in 87.6% of the women at the study visit, whereas only 16% of the overall sample had been previously diagnosed with the condition. Vaginal dryness (72.7%), vulvar burning sensation or itching (58.0%) and dyspareunia (52.7%) were the most prevalent symptoms. Pelvic signs consisted of vaginal dryness (89.1%), loss of vaginal rugae (80.6%) and vulvovaginal pallor (86.9%). However, only 31.3% of the participants had discussed genitourinary symptoms with their health-care professionals (HCPs). Regarding management, only 11.1% of women had prior experience with any form of therapy, and currently only 8.7% were receiving treatment. CONCLUSION: GSM is highly prevalent in this Greek perimenopausal/postmenopausal population. Nevertheless, the majority of women remain undiagnosed and untreated. Education for both women and HCPs regarding GSM will lead to improved diagnosis and better management of this syndrome.

Congenital anomaly and perinatal outcome following blastocyst- vs cleavage-stage embryo transfer: systematic review and network meta-analysis.

OBJECTIVES: To compare the reported rate of any congenital anomaly and perinatal outcome of pregnancy following blastocyst- vs cleavage-stage embryo transfer using a pairwise meta-analysis and to evaluate the same outcomes following fresh-blastocyst, frozen-blastocyst, fresh-cleavage or frozen-cleavage embryo transfer using a network meta-analysis. METHODS: A literature search was performed in PubMed, Scopus and CENTRAL and registers for ongoing studies, from inception to February 2022, for randomized controlled trials (RCTs) with any sample size and observational studies including at least 100 live births per group, comparing the rates of any congenital anomaly and perinatal outcome of pregnancy following fresh/frozen embryo transfer at cleavage (day 2-3) vs blastocyst (day 5-7) stage. Risk ratios (RRs) along with their 95% CIs were pooled via a random-effects model meta-analysis. Within a frequentist network meta-analysis framework, outcomes of all four treatment modalities (i.e. fresh-blastocyst, fresh-cleavage, frozen-blastocyst, frozen-cleavage) were compared further. Any congenital anomaly constituted the primary outcome, whereas preterm delivery (delivery < 37 weeks), low birth weight (LBW; < 2500 g), gender of the neonate (male), perinatal death and healthy neonate (defined as liveborn neonate, delivered at term, weighing ≥ 2500 g, surviving for at least 28 days postbirth and without any congenital anomaly) were considered as secondary outcomes. Subgroup analyses by plurality (liveborn singleton vs multiple pregnancy) were conducted in the pairwise and network meta-analyses. The risk of bias was assessed using the RoB2 tool for RCTs and the ROBINS-I tool for non-randomized studies. Certainty of evidence was assessed using GRADE. RESULTS: Through the literature search, 550 studies were retrieved and 33 were included in the systematic review. We found no significant difference in the risk for any congenital anomaly between blastocyst- and cleavage-stage transfer (RR, 0.80 (95% CI, 0.63-1.03); 10 studies; n = 192 442; I2 = 85.5%). An increased probability of a male neonate was observed following blastocyst- vs cleavage-stage transfer (RR, 1.07 (95% CI, 1.06-1.09); 18 studies; n = 227 530; I2 = 32.7%). No significant differences in other secondary outcomes or significant subgroup differences between liveborn singletons and multiple pregnancies were observed. The network meta-analysis showed a significantly lower risk for LBW following frozen-blastocyst vs fresh-blastocyst (RR, 0.76 (95% CI, 0.60-0.95)) or fresh-cleavage (RR, 0.74 (95% CI, 0.59-0.93)) transfer. Frozen-blastocyst transfer was associated with an increased risk for perinatal death compared with the fresh-cleavage method (RR, 2.06 (95% CI, 1.10-3.88)). The higher probability of a male neonate following blastocyst transfer remained evident in the network comparisons. All outcomes were assessed to be of very-low certainty of evidence. CONCLUSIONS: Current very-low certainty of evidence shows that there may be little-to-no difference in the risk for congenital anomaly or adverse perinatal outcome of pregnancy following blastocyst- vs cleavage-stage embryo transfer, although there was a slightly increased probability of a male neonate following blastocyst transfer. When considering cryopreservation, frozen-blastocyst transfer was associated with a reduction in the risk for LBW compared with both fresh-transfer modalities, and fresh-cleavage transfer may be associated with a reduction in the risk for perinatal death compared with frozen-blastocyst transfer. High-quality RCTs with separate data on fresh and frozen cycles and consistent reporting of culture conditions and freezing methods are mandatory. Individual participant data meta-analyses are required to address the substantial inconsistency resulting from current aggregate data approaches. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Should the flexibility enabled by performing a day-4 embryo transfer remain as a valid option in the IVF laboratory? A systematic review and network meta-analysis.

PURPOSE: The present systematic review and network meta-analysis aims to uniquely bring to literature data supporting the true place of the alternative practice of day-4 embryo transfer (D4 ET) in an IVF laboratory, beyond the one-dimensional option of facilitating a highly demanding program. METHODS: A systematic search was conducted in the databases of PubMed/Medline, Embase, and Cochrane Central Library, resulting to six prospective along with nine retrospective cohort studies meeting eligibility criteria for inclusion. A comparison of D4 ET with day-2 (D2), day-3 (D3), and day-5 (D5) ET, respectively, was performed employing R statistics. RESULTS: The sourced results indicate no statistically significant difference regarding clinical pregnancy rates, and ongoing pregnancy/live birth rates stemming from the comparison of D4 with D2, D4 with D3, and D4 with D5 ET, respectively. Additionally, no statistically significant difference could be established in respect to cancelation, and miscarriage rates, following the comparison of D4 with D3 and D4 with D5 ET. Interestingly, we report statistically significant lower preterm birth rates associated with D4 ET, in contrast with D5 ET (RR, 0.19; 95% CI, 0.05-0.67; p value = 0.01). CONCLUSIONS: The aforementioned results may serve as advocates buttressing the option of D4 ET as a valid candidate in the ET decision-making process. Possible limitations of the current study are the publication bias stemming from the retrospective nature of certain included studies, along with various deviations among studies' design, referring to number and quality of transferred embryos, or different culture conditions referring to studies of previous decades.

Changing the way we train surgeons in the 21th century: A narrative comparative review focused on box trainers and virtual reality simulators.

The traditional method of acquiring surgical skills by observing and assisting in surgical procedures involving human beings has been challenged during the past several years. Lessons obtained from aviation suggested that the use of simulators is related to reduced costs, increased efficiency in performing certain tasks and above all safety. A shift in paradigm is also required in modern surgical training. The development of endoscopic surgery allowed for the incorporation of medical simulators into training programmes. A review of the literature was conducted using specific inclusion and exclusion criteria, for articles published up to July 31th, 2018. Relevant studies were identified using computerized bibliographic searches of MEDLINE database. The keywords that were used in various combinations were: "Medical Simulators", "Surgical Training", "Laparoscopy", "Surgical Skills", "Box trainers", "Virtual reality simulators", "Surgical Education". Surgical training with box trainers and/or virtual reality simulators confers a significant benefit in terms of surgical skills development, increases patient safety and reduces costs. Nevertheless, the use of virtual reality simulators was significantly more expensive. Simulation training allows trainees to learn from their mistakes, to repeat surgical tasks multiple times so as to establish muscle memory, and enhance skill competency with the aid of informative feedback. Simulators are necessary for the development of the skills required to meet the specific needs of endoscopic surgery in the 21st century. Teaching hospitals should introduce simulation training programmes in order to increase efficiency, reduce costs and improve patient safety. As medical advancements continue to transform the way we perform surgery day by day, simulation training will play a pivotal role in every surgical specialty.

Assessment of follicle viability using fluorescence microscopy before and after ovarian thawing.

The incidence of young women diagnosed with cancer has been globally increasing. In many cases the surgical approach followed by chemotherapy, radiotherapy or hormonal therapy could lead to infertility or premature ovarian failure. Several options are available in order to preserve fertility and increase the future gestation rate. Among embryo cryopreservation and oocyte cryopreservation, ovarian tissue cryopreservation represents an ideal option, especially for premenopausal women and for those who cannot delay the start of chemotherapy. The purpose of this study was to examine the follicle viability using fluorescence microscope before and after ovarian thawing.

Laparoscopic excision of rectosigmoid endometriotic plaque and cul de sac obliteration in deeply infiltrating endometriosis: a case report.

Endometriosis represents a main cause of infertility and pelvic pain affecting 3-43% among reproductive age women. Deep pelvic endometriosis is defined as subperitoneal infiltration of endometrial implants in the uterosacral ligaments, rectum, rectovaginal septum, vagina or bladder. The authors present a case of a 29-year-old patient who underwent laparoscopic excision of extensive endometriotic plaque in rectovaginal septum accompanied with deeply infiltrating endometriosis (DIE) and chronic pelvic pain (CPP).

Endometriosis and ovarian cancer: clinical and molecular aspects.

Endometriosis is one of the most commonly encountered benign problems in gynecology. Even though endometriosis appears to predispose to ovarian cancer the progression from atypical epithelial proliferation (atypical endometriosis and metaplasia), to the formation of well-defined borderline tumors and finally to endometrioid ovarian cancer will take several years. To elaborate on the concept of endometriosis as a precursor of some types of ovarian cancer, we present an overview of the pathophysiological and genetic characteristics, common in those two conditions. Furthermore, we present the genetic mutations found in ovarian cancers and we outline the common genetic alterations of endometriosis and ovarian cancer, focusing on the PI3K/Akt/mTOR-signaling pathway.

Preimplantation genetic diagnosis in marfan syndrome.

Marfan syndrome (MFS) is a systemic hereditable disorder of the connective tissue with mainly cardiovascular manifestations, such as aortic dilatation and dissection. We describe a case of a 32-year-old Caucasian woman, clinically asymptomatic with MFS who presented for genetic consultation to prevent the transmission of disease to her offspring. She underwent controlled ovarian stimulation (COH), in vitro fertilization (IVF) combined with preimplantation genetic diagnosis (PGD), and a singleton pregnancy with positive fetal heart rate was revealed. At 34 weeks' gestation she delivered vaginally a healthy premature male infant weighting 2440 gr. The patient remained asymptomatic during pregnancy, delivery, and 3 months postpartum. It is has to be mentioned that the availability of PGD is essential to prevent the transmission of disease to the next generation.

Successful management of evisceration occurred after exploratory laparotomy for bilateral ovarian micropapillary serous borderline tumors.

Micropapillary serous borderline tumor of the ovary is characterized by a more frequent association with extraovarian, especially invasive, implants. The aim of this study was to report the clinicopathological findings of a rare case of micropapillary serous borderline tumor of the ovary since there are less than 100 similar cases in the published literature. Additionally, the successful management of evisceration that complicated the postoperative stay of the patient is analyzed. The incidence of this severe complication is estimated between 0.29-2.3%. There are four main causes: suture tearing through the fascia, knot failure, suture failure, and extrusion of abdominal contents between sutures placed too far apart. At least 50% of the cases are due to technical error with a potentially lethal result.

Laparoscopic management of large ovarian cysts.

The aim of this study was to describe a new technique for laparoscopic removal of large ovarian cystic masses. The authors performed a retrospective study during the period January 2008 to December 2009 in the Second Department of Obstetrics and Gynecology of Aretaieion University Hospital; 19 women with large ovarian cysts were included in the study. During the study period, 53 women underwent laparoscopic excision of ovarian cysts. Among them, 19 had very large complex ovarian cysts with a mean diameter of 8.4 cm. The mean age of the patients was 32.1 years. Ultrasound examination revealed findings suggestive of benign disease in all patients. In 8 out of 19 patients CA-125 levels were elevated, ranging from 40.5 to 194.7 IU/mL. A 5-mm suprapubic trocar was directly inserted into the cyst and fluid contents aspirated, so the decompressed cyst could fit in a 5-cm laparoscopic bag. The cyst wall was carefully detached from the healthy ovarian tissue and placed in the bag without any spillage. The remaining cyst wall was removed from the peritoneal cavity with the laparoscopic bag. The mean operative time was 45 minutes. No operative or postoperative complications were noted. There was no conversion to laparotomy. Mean hospital stay was 1 day. Pathology revealed 7 endometriomas, 3 mucinous cystadenomas, 3 serous cystadenomas, 3 serous cysts, and 3 teratomas. Direct trocar insertion within the ovarian cyst followed by aspiration of the fluid contents is a safe and feasible method for the laparoscopic management of large ovarian cysts.

An oocyte donation protocol using the GnRH antagonist ganirelix acetate, does not compromise embryo quality and is associated with high pregnancy rates.

PURPOSE: To evaluate the effect of the GnRH antagonist, ganirelix acetate, on oocyte quality. METHODS: Stimulation characteristics, implantation rates and clinical pregnancy rates were compared between 29 oocyte donors 21-31 years of age who underwent 31 cycles of ovarian stimulation with gonadotropins and ganirelix acetate, and 36 infertile couples of similar age range who underwent 51 cycles of ovarian stimulation using the same protocol. RESULTS: A significantly lower number of embryos were transferred in the donor/recipient group as compared to the infertile group (2.32+/-0.54 vs. 2.82+/-0.71, P<0.05). In contrast, implantation and clinical pregnancy rates per transfer, were significantly higher in the donor/recipient group (38.1% vs. 10.4%, P<0.01) and (61.3% vs. 23.1%, P<0.05) respectively, as compared to the infertile group. CONCLUSIONS: Incorporation of ganirelix acetate for pituitary suppression in stimulation protocols for oocyte donation is associated with high pregnancy rates suggesting that ganirelix acetate does not exert an adverse effect on oocyte or embryo quality.

Prolactin receptor gene expression and immunolocalization of the prolactin receptor in human luteinized granulosa cells.

Prolactin is mainly known for its role in breast development and lactation, but has been also implicated in other physiological functions such as immunoregulation and ovarian steroid production. Although prolactin and prolactin receptor (PRL-R) transcripts have been previously identified in the human ovary, the spatial localization of the receptor is unknown. To investigate the presence of PRL-R within the follicular apparatus, human luteinized granulosa cells were obtained at the time of follicular aspiration from women undergoing ovarian stimulation for IVF. RNA extracted from these cells was subjected to reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primers for the PRL-R gene. In addition, paraffin sections of isolated granulosa cells and sections of premenopausal human ovaries were immunostained with a mouse anti-human PRL-R monoclonal antibody. PRL-R were immunolocalized to the cell membrane of isolated luteinized granulosa cells and PRL-R transcripts were detected in the extracted RNA. No detectable staining was noted in secondary and early antral follicles in archived paraffin sections. These findings confirm the presence of PRL-R in human luteinized granulosa cells and suggest a localized role for PRL within the mature follicle. The absence of PRL-R in the early follicle suggests that the effects of prolactin are exerted around the time of ovulation.

Clinical significance of the qualification of atypical squamous cells of undetermined significance: An analysis on the basis of histologic diagnoses.

OBJECTIVE: This study was undertaken to evaluate the significance of further qualification of atypical squamous cells of undetermined significance in routine Papanicolaou smears. STUDY DESIGN: A retrospective medical records review was conducted on 316 women whose Papanicolaou smears yielded diagnoses of either atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion or atypical squamous cells of undetermined significance suggestive of a reactive process. RESULTS: The overall incidence of a squamous intraepithelial lesion (cervical intraepithelial neoplasia grades I, II, and III) was higher in the group with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion than in the group with results suggestive of a reactive process (41.1% vs 22.3%; P =.0344). Women with atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion were 9.7 times more likely to have high-grade squamous intraepithelial lesion (cervical intraepithelial neoplasia III) develop than were women with atypical squamous cells of undetermined significance suggestive of a reactive process (95% confidence interval, 1.26-74.64). The incidence of high-grade squamous intraepithelial lesion was higher among women 35 years old (17.8% vs 6.3%; P =.0378). CONCLUSION: Women with a diagnosis of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion are more likely to have intraepithelial lesions develop than are those with atypical squamous cells of undetermined significance suggestive of a reactive process. Aggressive evaluation of cases of atypical squamous cells of undetermined significance suggestive of the presence of an intraepithelial lesion with colposcopy and cervical biopsies may be appropriate. Age should be considered as an independent factor in the plan of management.

The ovarian hyperstimulation syndrome.

OBJECTIVE: To review the up-to-date literature concerning the pathogenesis of, risk factors for, prevention of, and therapy for the ovarian hyperstimulation syndrome, and to provide suggestions for management of this syndrome. DESIGN: Literature review combined with on-site clinical experiences at the authors' institution of practice. PATIENT(S): Women who have risk factors for or manifest the ovarian hyperstimulation syndrome. INTERVENTION(S): Intravenous fluid management, thrombosis prevention techniques, paracentesis techniques, and critical care management protocols. MAIN OUTCOME MEASURE(S): Staging system of the ovarian hyperstimulation syndrome, criteria for outpatient versus hospitalization management, and indications for varying levels of interventional management. RESULT(S): The ovarian hyperstimulation syndrome, unique to the field of assisted reproductive technology, remains a largely elusive and unpredictable iatrogenic physiologic complication in the course of pharmacologic ovarian stimulation. Reliable information on risk factors, possible physiologic mechanisms, prevention techniques, and management is fortunately progressing, and overall advances are being made in this field. The present review is an attempt to summarize the modern literature regarding this syndrome and to use this current knowledge to provide a basis for acceptable management regimens. CONCLUSION(S): Ovarian hyperstimulation syndrome is a serious complication of assisted reproductive technology, with potential for critical morbidity and death. Physicians who prescribe medications known to be associated with this syndrome should be familiar with identifiable risk factors, means of prevention, and a system for staging and treating the disease and have a current knowledge base for putative models of pathogenesis.

Exogenous luteinizing hormone (LH) increases estradiol response patterns in poor responders with low serum LH concentrations.

PURPOSE: Our purpose was to investigate whether the addition of exogenous leuteinizing hormone (LH) increases estradiol secretion in LH-depleted women undergoing controlled ovarian hyperstimulation (COH) with purified follicle stimulating hormone (FSH). METHODS: We carried out case series and retrospective analysis of midfollicular serum LH concentrations and estradiol response patterns in COH cycles. All patients initially received gonadotropins containing purified FSH. Human menopausal gonadotropin containing LH was added to poor responders with low midfollicular LH concentrations. RESULTS: The addition of exogenous LH to the COH regimen significantly increased estradiol secretion in poor responders with low midfollicular endogenous LH concentrations. This was confirmed statistically by an average change in the slope of the estradiol patterns from 27.54 to 85.49 after the addition of exogenous LH. Furthermore, patients with midfollicular serum LH concentrations < 3.0 mIU/ml had significantly lower midfollicular and peak estradiol (E2) concentrations compared to patients with LH concentrations > or = 3.0 mIU/ml (352.3 and 2094.3 vs 855.6 and 3757.1 pg/ml, respectively). CONCLUSIONS: The addition of exogenous LH increases E2 response patterns in poor responders with low midfollicular serum LH concentrations. Low midfollicular serum LH concentrations are associated with significantly lower midfollicular and peak E2 concentrations.

Cervical sarcoma botryoides. A case report.

BACKGROUND: Sarcoma botryoides is a rare gynecologic malignancy. Reported treatment protocols range from localized resection of the tumor to radical surgery and adjuvant chemotherapy. Recently, limited excisional surgery combined with chemotherapy has contributed to excellent survival rates and preserved bladder and rectal function. CASE: We report a case of cervical sarcoma botryoides with minimal invasion. The patient had primary surgical treatment with complete resection of the tumor without adjuvant chemotherapy. Four months after surgery she presented with extensive metastatic retroperitoneal disease and died two weeks later. CONCLUSION: The clinical course of this patient suggests that complete surgical resection in cases of localized disease is not adequate therapy for sarcoma botryoides. Adjuvant chemotherapy should always be used, even at a very early stage.

Color and pulsed Doppler sonography, gray-scale imaging, and serum CA 125 in the assessment of adnexal disease.

OBJECTIVE: To compare color and pulsed Doppler sonography with gray-scale ultrasound imaging and serum CA 125 levels in establishing accurate preoperative diagnoses of adnexal masses. METHODS: Medical records of 109 patients referred with preexisting adnexal lesions were reviewed retrospectively by comparing preoperative ultrasonic data (gray-scale imaging and color and pulsed Doppler findings) with serum CA 125 levels. RESULTS: Eighty-three masses were removed surgically, confirming seven malignancies and 76 benign tumors, and 26 masses were followed; 15 regressed and 11 persisted. Color and pulsed Doppler sonography showed the highest sensitivity, followed by gray-scale imaging, whereas serum CA 125 levels revealed the highest specificity in distinguishing malignant from benign adnexal tumors. All three methods had high negative predictive values (96-100%), whereas only serum CA 125 had a positive predictive value greater than 50%. CONCLUSION: Color and pulsed Doppler sonography, which demonstrate a tumor angiogenic activity, are as accurate as gray-scale imaging in the assessment of adnexal lesions. Together with serum CA 125 marker levels, they produce high negative predictive values, providing reassurance that an adnexal mass is benign.