Does fertility treatment increase the risk of uterine cancer? A meta-analysis.

An ongoing debate over the last two decades has focused on whether fertility treatment in women may lead to an increased risk of developing uterine cancer over a period of time. Uterine cancer (including mainly endometrial carcinoma and the less common uterine sarcoma) is the commonest reproductive tract cancer and the fourth commonest cancer in women in the UK. Our objective was to assess the association between fertility drugs used in the treatment of female infertility (both as an independent therapy and during in vitro fertilization cycles) and the development of uterine cancer. A literature search was performed using Medline, Embase, Cochrane Library and Google Scholar databases for comparative studies until December 2014 to investigate a clinical significance of fertility treatment on the incidence of developing uterine cancer. General and MESH search headings, as well as the 'related articles' function were applied. All comparative studies of 'fertility treatment' versus 'non-fertility treatment' reporting the incidence of uterine cancer as an outcome were included. Uterine cancer incorporated the following terms: uterine cancer, uterine body tumours, uterine sarcomas and endometrial cancers. The primary outcome of interest was the uterine cancer incidence in all 'fertility treatment' versus 'non-fertility treatment' patient groups. Secondary outcomes of interest were: (a) uterine cancer incidence in 'IVF' versus 'non-IVF' patient groups; and (b) uterine cancer incidence according to type of fertility drug used. Odds ratio was the summary statistic. Random-effects modelling, graphical exploration and sensitivity analysis were used to evaluate the consistency of the calculated treatment effect. We included six studies in our final analysis, which comprised 776,224 patients in total. Of these, 103,758 had undergone fertility treatment and 672,466 had not. There was 100% agreement between the two reviewers regarding the data extraction. All the studies contained groups that were comparable in age, although the criteria of reporting age varied. Taking all studies into account, the incidence of uterine cancer was 0.14% (150 of 103,758) in the fertility treatment group and 2.22% (14,918 of 672,466) in the non-fertility treatment group. Using the random-effect model to analyze uterine cancer incidence, this difference was not found to be of statistical significance: OR 0.78 (95% CI, 0.39-1.57). The degree of heterogeneity was high (I(2)=68%). The risk for the development of uterine and in particular endometrial cancer posed by infertility and an unopposed oestrogen state is widely recognized. The present analysis aimed to perceive whether standard fertility drugs were also a risk to future uterine cancer development. The treatment does increase the concentrations of unopposed oestrogen for a short periods of time but if successful leads to fertility. This meta-analysis points to a non-deleterious effect of fertility drugs towards the development of uterine cancer, a conclusion strongly supported by our sub-group analysis.

Survey of perceptions of health care professionals in the United Kingdom toward uterine transplant.

CONTEXT: Currently, the only 2 options that women with absolute uterine factor infertility have for managing their infertility are surragocy or adoption. These women may also benefit from a possible future third option: uterine transplant. OBJECTIVE: To investigate the opinions and views of UK health care professionals toward uterine transplant and rank issues related to uterine transplant by importance in order to make uterine transplant transparent and understandable to colleagues. DESIGN: Large, in-depth survey investigating health care professionals' opinions on uterine transplant. SETTING: Analysis done at Imperial College London. PARTICIPANTS: UK transplant professionals (surgeons, nurses, operating room staff, and donor coordinators) and obstetricians and gynecologists (trainees, members, and fellows of the Royal College of Obstetricians and Gynaecologists). INTERVENTION: Questionnaires were given out at hospital grand rounds, trainee teaching days, and conferences (national and international). MAIN OUTCOME MEASURES: Should uterine transplant take place? Is uterine transplant achievable? What is the rank order of importance of key issues related to uterine transplant? RESULTS: The study had 528 participants. With respect to overall support for uterine transplant and as a possible future therapeutic option for absolute uterine factor infertility, 93.8% (n=495) thought that uterine transplant should take place if considered appropriate medically, surgically, and ethically and 57.2% (n=302) thought it was an achievable objective. Issues related to immunology of uterine transplant and pregnancy after uterine transplant were unanimously thought of as most important. More effort is required to educate health care professionals about all aspects of uterine transplant.

Trachelectomy during pregnancy: what has experience taught us?

The treatment of early stage cervical malignancy in a pregnant patient remains a challenge. We report the successful application of a vaginal radical trachelectomy (VRT) during pregnancy to treat a patient diagnosed with early stage cervical cancer and subsequently review the published work. A 22-year-old female diagnosed at the gestational age of 17 weeks with International Federation of Gynecology and Obstetrics stage IB1 squamous cell cervical carcinoma was treated with VRT at 19(+5) weeks. At 36 weeks, the patient underwent a scheduled cesarean section. A healthy male infant was delivered with a weight of 2795 g. After 13 months of follow-up, the patient is doing well with no evidence of recurrent disease.

Pregnancy after laparoscopic bilateral partial ovarian decortication for stage IC borderline ovarian tumour.

BACKGROUND: Fertility preservation techniques are a growing area of research as more women in the reproductive age group develop gynaecologic cancers. We report here a novel technique of fertility preservation used in the treatment of a patient with borderline ovarian tumour. CASE: A 29-year-old woman with stage I borderline ovarian tumour was referred to our tertiary level hospital. She had a history of infertility and requested fertility preservation be considered in treatment decisions. We performed bilateral laparoscopic partial decortication of the ovaries, and the patient successfully conceived spontaneously following the procedure. CONCLUSION: Fertility-preserving surgery should be an option for young women with borderline ovarian tumours who wish to retain fertility. Removing abnormal ovarian tissue may restore fertility. The laparoscopic approach is safe and feasible for these patients.

Contexte : Les techniques de préservation de la fertilité constituent un champ de recherche en évolution, de plus en plus de femmes en âge de procréer étant atteintes de cancers gynécologiques. Nous nous penchons sur une technique novatrice de préservation de la fertilité utilisée dans le cadre de la prise en charge d'une patiente présentant une tumeur ovarienne à la limite de la malignité. Cas : Une femme de 29 ans présentant une tumeur ovarienne à la limite de la malignité de stade I a été orientée vers notre hôpital de niveau tertiaire. Elle présentait des antécédents d'infertilité et souhaitait que la préservation de la fertilité soit prise en considération dans le cadre du processus de prise de décision quant au traitement. Nous avons pratiqué une décortication laparoscopique bilatérale partielle des ovaires et la patiente a été en mesure de connaître une grossesse spontanée à la suite de l'intervention. Conclusion : La chirurgie visant à préserver la fertilité devrait constituer une solution possible pour les jeunes femmes présentant une tumeur ovarienne à la limite de la malignité qui souhaitent demeurer fertiles. L'excision de tissus ovariens anormaux pourrait permettre de rétablir la fertilité. L'approche laparoscopique est sûre et praticable dans le cas de ces patientes.

Adding L-carnitine to clomiphene resistant PCOS women improves the quality of ovulation and the pregnancy rate. A randomized clinical trial.

OBJECTIVE: To evaluate the effectiveness of L-carnitine on improving the ovulation and pregnancy rates as well as adverse metabolic indices in clomiphene-resistant PCOS. DESIGN: Single center, double blinded, superiority, randomized controlled clinical trial. SETTING: Women's Health Hospital, Assiut University. METHODS: One hundred and seventy women diagnosed with PCOS were found to be clomiphene resistant. The women were randomly allocated into two groups: Group A (n=85), where patients received 250 mg clomiphene citrate from day three until day seven of the cycle plus L-carnitine (LC) 3g daily; and Group B (n=85) received 250 mg clomiphene citrate with placebo. OUTCOME: Primary outcome is cumulative clinical pregnancy rate. Secondary outcomes are changes in serum glucose level and lipid profile. RESULTS: The combination of L-carnitine and CC significantly improve both the ovulation and the cumulative pregnancy rates in clomiphene resistant PCOS (55 (64.4%) vs. 15 (17.4%) and 44 (51.5) % vs. 5 (5.8) %). The number of stimulated follicles reaching ≥17 mm diameter was significantly more in Group A to Group B (2.2 ± 0.77 vs. 0.16 ± 0.79; p<0.0001). Group A needed significantly fewer days for adequate follicular maturation, had a thicker endometrium and higher oestradiol concentration at the time of human chorionic gonadotrophin injection (10.1 ± 0.1mm vs. 6.8 ± 0.4mm; p<0.0001). The same group had a higher mean luteal-phase serum progesterone compared with the control group (13.55 ± 0.99 vs. 10.6 ± 0.98 ng; p<0.0001). A significant difference was found regarding the clinical pregnancy rates (42 (49.4%) vs. (1) 1.1% respectively p value <0.0001). CONCLUSION: Adding L-carnitine when treating clomiphene-resistant PCOS patients not only improved the quality of ovulation and the pregnancy rate with an acceptable patient tolerability, but also enhanced the patient lipid profile and body mass index.

Is there a role for transplantation in gynecologic oncology? Autotransplantation and other lessons.

We describe an exciting and novel surgical option, which may be used to treat formerly unresectable masses. This process is commonly referred to as autotransplantation (AuTn), and it combines the advances in transplant medicine and applies them to surgical oncology. The idea behind AuTn is the removal of the cancerous organ(s) to allow complete anatomic resection of the tumor mass, with consequent anastomotic reimplantation or AuTn of the now macroscopically tumor-free organ back into the patient. Autotransplantation has been used to remove large fibromatosis and desmoid tumors as well as malignant tumors. Our belief is that using lessons learned from the field of transplantation, AuTn can be applied in gynecologic oncology.

Elevated and secreted phospholipase A2 activities as new potential therapeutic targets in human epithelial ovarian cancer.

Ascites in epithelial ovarian cancer (EOC) promotes tumor development by mechanisms that are incompletely understood. Lysophosphatidic acid (LPA), a major tumor-promoting factor in EOC ascites, is an enzymatic product of autotaxin (ATX) and phospholipase A(2) (PLA(2))enzymes. The contribution of PLA(2) activities to ovarian tumorigenesis was investigated. The quantitative measurement of PLA(2) activities in ascites and tissues, as well as assay conditions selective for PLA(2) subtypes, were optimized and validated. PLA(2) activities correlated with tumor-promoting activates in cell-based and in vivo assays. High activities consistent with both cytosolic and calcium-independent PLA(2) were found in human EOC ascites for the first time. Elevated PLA(2) and ATX activities were also observed in EOC compared to benign tumors and normal tissues. Cell-free and vesicle-free (S4) human EOC ascites potently promoted proliferation, migration, and invasion of human EOC cells in a PLA(2)-dependent manner. LPA mediated a significant part of the cell-stimulating effects of ascites. S4 ascites stimulated tumorigenesis/metastasis in vivo, and methyl arachidonyl fluorophosphonate was highly effective in inhibiting EOC metastasis in mouse xenograft models. PLA(2) activity was found in conditioned media from both EOC cells and macrophages. Collectively, our work implies that PLA(2) activity is a potential marker and therapeutic target in EOC.

One port laparoscopic technique for interval placement of intraperitoneal chemotherapy port under direct visualization.

PURPOSE: In an effort to minimize catheter-related complications we present a 1-port laparoscopic procedure for interval placement of an intraperitoneal chemotherapy catheter under direct visualization. METHODS: A single 5-mm laparoscopic port is placed in the umbilicus. A 5-cm incision is made in the midaxillary line and a pocket is created to hold the intraperitoneal chemotherapy port. The introducer is then tunneled from the pocket towards the umbilicus and is used to pierce the fascia under direct visualization. It is then tunneled towards the camera and removed through the umbilical port. The catheter is cut and allowed to fall back into the abdomen under direct visualization. RESULTS: No patient had their chemotherapy regimen altered because of catheter-related complications. Specifically, there were no other infections, leakage, blockage, or access problems. CONCLUSIONS: In selected patients, this may be considered as a new minimally invasive option.

Neoadjuvant chemotherapy followed by simultaneous robotic radical trachelectomy and reversal of tubal sterilization in stage IB2 cervical cancer.

INTRODUCTION: The aim of this study was to report a case of cervical cancer stage IB2 treated with neoadjuvant chemotherapy, followed by simultaneous robotic-assisted radical trachelectomy and reversal of tubal sterilization. CASE DESCRIPTION: This case occurred in a university hospital involving a 31-y-old woman with stage IB2 cervical cancer treated using neoadjuvant chemotherapy, robotic surgery, and tubal anastomosis to determine cancer disease status and achieve restoration of tubal patency. DISCUSSION: A successful radical trachelectomy with patent tubes was done bilaterally. Cancer and fertility procedures can be simultaneously implemented and achieved.