Fertility-sparing Treatment Research Articles

Fertility Sparing (Minimally Invasive) Treatment of Arteriovenous Malformation of the Uterus with Mullerian Anomaly

Arteriovenous malformation of the uterus is a rare condition that may be congenital or acquired. While hysterectomy is the definitive therapy, uterine artery embolization appears to be an effective uterine sparing option. More than 85 cases of embolization of uterine arteriovenous malformation have been reported. Restoration of normal menstrual cycles and successful pregnancies have been reported in 2 cases.

Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Clinical Trials Planning Meeting

The second Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Clinical Trials Planning Meeting was held on December 1, 2012, and included international multidisciplinary representatives of the 24 member groups. The aims were to review recent advances in molecular pathology of endometrial cancer, focusing on molecular-based therapy, and to identify key hypotheses and issues to be addressed through international collaborative clinical trials. Reviews and summaries of current knowledge were presented followed by parallel working group sessions for surgery, adjuvant and systemic therapy, and translational research. Plenary discussions were held to integrate translational and clinical issues, and a final discussion session to agree on key trial concepts. Proposals to take forward on the following trials were agreed: (1) lymphadenectomy to direct adjuvant treatment in women with high-risk endometrial cancer, including a sentinel node substudy; (2) conservative therapy for low-risk endometrial cancers in morbidly obese women with high surgical risks and for fertility-sparing treatment in premenopausal patients; (3) adjuvant therapy for women with early-stage carcinosarcoma. A proposal was made that a GCIG Early Phase Consortium be developed to serve as an international platform for rapid assessment of biomarkers.

Fertility sparing treatment of recurrent stage I serous borderline ovarian tumours

Here we report the outcomes of 26 patients who relapsed following conservative surgical treatment of stage I serous borderline ovarian tumours treated initially with fertility-sparing surgery. All recurrences were diagnosed by systematic ultrasonography during follow-up. Eleven patients relapsed at least twice after such management. Twenty-one pregnancies were observed in 13 patients. Eleven of these patients became pregnant after the treatment of their first recurrence. All patients had a borderline ovarian tumour and/or non-invasive peritoneal implants at the time of the first recurrence but two of them had invasive ovarian and peritoneal disease at the time of the second or third recurrence (one of them died of disease). Fertility-preserving surgery remains a valuable alternative (if technically feasible), in young patients with recurrent SBOT, in the form of a non-invasive ovarian lesion, who wish to start a pregnancy. However, it should be associated with meticulous follow-up because the risk of progression to carcinoma exists, albeit small.

Fertility-sparing treatment of localized gynecologic malignancies results in many successful pregnancies yet overall infertility and menopause rates remain increased

Fertility-sparing treatment of localized gynecologic malignancies results in many successful pregnancies yet overall infertility and menopause rates remain increased

Women managed with fertility-sparing treatment for gynecologic cancers face an increased risk of miscarriage

OBJECTIVE: To determine whether serum b-hCG assays on cycle day (CD) 24 and 26 can be used to predict IVF pregnancy outcome. DESIGN: Retrospective cohort. MATERIALS AND METHODS: All IVF patients were scheduled for luteal blood draws on CD 24 and 26. Pregnant patients from 1/04 to 12/11 who had CD 24, 26, and 28 bloods drawn (n1⁄42571) after fresh IVF were identified. Pregnancy outcomes were compared between patients whose first positive b-hCG (>5mIU/mL) occurred on CD 24 versus 26, and between patients with and without b-hCG doubling from CD 24 to 26, and 26 to 28. ROC curves were constructed for b-hCG levels on CD 24 and 26 as predictors of clinical pregnancy. Outcomes in the doubling analysis were stratified according to b-hCG value ( 50) on CD 28 for women 5. Those with CD 26 b-hCG 5. Patients with b-hCG doubling from CD 24 to 26 had a significantly higher CPR (88% vs. 20%, P 50 had a LBR of 84%. CONCLUSION: CD 24 and 26 b-hCG levels are useful for predicting pregnancy outcome in IVF patients. More work should be done to see whether absent b-hCG on CD 24 and CD 26 represents delayed implantation or poor intrinsic embryo viability.

Endometrial cancer in young patients: report of 17 cases

Endometrial cancer of young (less then 40 years old) patients comprises 4-5% of all endometrial cancers in Hungary. The majority of patients did not give birth yet, so fertility sparing is very important. Fertility sparing treatment is possible if the tumor's histology is endometrial type and Grade 1 (well differentiated). The tumor localizes only to the endometrium and there is no myometrium infiltration. The authors present 17 cases of patients treated at the Department of Gynecology of National Institute of Oncology (Budapest, Hungary). In 3 cases conservative therapy (progesterone treatment) was possible, and 14 patients had to undergo surgery, because conservative treatment did fail. Of 17 patients 14 were never pregnant. The average patient's age was 32.35 ± 4.27 years. The mean body weight was 93.13 ± 30.79 kg (from 58 kg up to 147 kg); in 7 cases BMI (body mass index) was more than 30. After surgery histological examination had revealed 2 cases with normal ovaries, 1 case of simple cyst and 1 case of malignant ovarian tumor (serous adenocarcinoma, Grade 2), and 10 cases of polycystic ovaries associated with endometrial cancer. Of 3 cases that had only curettage, the endometrial cancer was Grade 1, and in 1 case radiological imaging showed simplex ovarian cyst. The authors' findings concerning young endometrial cancer patients confirm the results published in the literature. In cases suitable for fertility sparing treatment it is not sufficient to concentrate only on endometrial findings, but is very important to focus on the therapy of cystic ovaries (80% of which is PCO), obesity and diabetes mellitus as well.

Androgen-producing steroid cell ovarian tumor in a young woman and subsequent spontaneous pregnancy

To describe the presentation and fertility sparing treatment of a young woman found to have a steroid cell tumor not otherwise specified (NOS) and her spontaneous pregnancy and delivery shortly after surgery. A 20-year-old Hispanic female presented with hirsuitism, virilization, and elevated androgen levels (testosterone 328ng/dL) and was wrongly diagnosed with polycystic ovarian syndrome. Four months later she sought a second opinion. Her androgens were as follows: testosterone level 485ng/dL, androstenedione 1,738ng/dL and DHEA 1,459ng/dL. She had normal levels of progesterone, estradiol, and DHEA-SO4. On transvaginal ultrasound she had a solid-appearing right ovarian mass. She underwent fertility sparing surgery with a laparoscopic right oophorectomy. Gross and histological pathology confirmed a benign steroid cell tumor NOS. She had rapid normalization of all androgens 13days after surgery. She had spontaneous resumption of menses 4months later. She conceived despite using emergency contraception approximately 9months following surgery and delivered a healthy boy at term without complication. Prompt evaluation for an androgen producing tumor should be performed when testosterone levels are greater than 200ng/dL. Pregnancy following removal of this rare tumor has not previously been reported.

Less Radical Surgery for Patient With Early-Stage Cervical Cancer

IntroductionSurgery in cervical cancer should be used with intention of cure. Radical abdominal trachelectomy is a feasible operation for selected patients with stage Iα-1β cervical cancer which fertility can be preserved.Case ReportA 30-years-old woman with squamous cell cervical cancer stage (1 A II) diagnosed at September 2011 expressed a wish for fertility-sparing treatment. Radical abdominal hysterectomy and pelvic and para-aortic lymphadenectomy were performed which showed no evidence of lymphatic metastasis. Subsequently, at last follow-up (5 months post-surgery), good oncologic outcomes were found after this procedure. This was the first case of fertility-sparing radical trachelectomy procedures performed at our institution.ConclusionsTrachelectomy represents a valuable conservative surgical approach for early stage invasive cervical cancer.

Pregnant rate and pregnancy-relating factors of patients with early endometrial carcinoma and severe atypical hyperplasia of endometrium after fertility-preserving treatment by progestin

To summarize the pregnant rate of patients with early endometrial carcinoma and severe atypical hyperplasia after fertility-preserving treatment and analyze their pregnancy-relating factors. Endometrial curettage was used to evaluate the therapy response of endometrium after every 3 months of administration of high-dose progestin as fertility-sparing treatment for 51 patients with stage I endometrial carcinoma or severe endometrial atypical hyperplasia from Jun. 1996 to Jan. 2010. Individualized maintained treatment was given to patients after achieving complete remission of the endometrium. Pregnant results and pregnancy-relating factors were analyzed retrospectively. The median age of all the 51 patients was 29 years old. Forty-five (88%, 45/51) achieved complete response. Of the 34 cases who desired to conceive after complete response, 16 of them had 22 pregnancies, the pregnant rate was 47% (16/34); and 12 women obtained healthy live birth baby, the fertility rate was 35% (12/34). The pregnant rate of patients at age >35 or ≤ 35 was 0/2 and 50% (16/32) respectively (P > 0.05). The pregnant rate of patients with or without infertility was 40% (8/20) and 8/14, with endometrial cancer or severe atypical hyperplasia was 40% (10/25) and 6/9, respectively (all P > 0.05). The pregnant rate of patients who received in vitro fertilization-embryo transfer, ovulation promotion, or no treatment was 7/7, 6/16 and 3/11 respectively (P < 0.01). Fertility-preserving treatment for early endometrial cancer and severe atypical hyperplasia with high-dose progestin could achieve higher response rate. Assisted reproductive technologies could significantly increase the chance of conception.

Fertility-sparing treatment of complex atypical hyperplasia and low-grade endometrial cancer using oral progestin

Fertility-sparing treatment of complex atypical hyperplasia and low-grade endometrial cancer using oral progestin

Levonorgestrel-releasing intrauterine system for atypical endometrial hyperplasia

Endometrialcarcinomaisthemostcommongynaecologicmalignancyintheworldanddevelopsthroughpreliminarystagesofendometrialhyperplasia. Typicalendometrialhyperplasiasuggestsasignificantpre-malignantstatewithfrankprogressiontoendometrialcarcinoma. Because atypical endometrial hyperplasia tends to occur at a young age, it has become increasingly important and necessary to find a safe and effective fertility-sparing treatment with better tolerability and fewer side effects than the options for treatment that are currently available. Thelevonorgestrel-releasing intrauterinesystem hasalready beenusedto provide endometrial protection in women with breast cancer who are on adjuvant tamoxifen. The antiproliferative function of levonorgestrel is thought to reduce the risk of endometrial hyperplasia. Todeterminetheefficacyandsafetyofthelevonorgestrel-releasingintrauterinesysteminreversingatypicalendometrialhyperplasia. In November 2012 we searched the Cochrane Menstrual Disorders and Subfertility Review Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library; MEDLINE; EMBASE; and the China National Knowledge Infrastructure for relevant trials. Attempts were made to identify trials from references in published studies. We also searched for ongoing trials in five major clinical trials registries. Randomised controlled trials (RCTs) of the levonorgestrel-releasing intrauterine system(LNG-IUS) versus progestin therapy in women with a confirmed histological diagnosis of simple or complex endometrial hyperplasia with atypia. No eligible study was found. We did not identify any studies which met our full inclusion criteria. There is no evidence available from randomised controlled trials regarding the efficacy and safety of the levonorgestrel-releasing intrauterinesystem(LNG-IUS) foratypicalendometrialhyperplasia. RCTS are required to determine whether the LNG-IUS is safe and effective for treating atypical endometrial hyperplasia.

Predictability of later developed relapse in endometrial carcinoma in young women with functional imaging parameters of fes/FDG SUV ratio after fertility-sparing hormone treatment.

e16502 Background: Even in responders of fertility-sparing hormone treatment for uterine endometrial carcinoma (EC) and atypical endometrial hyperplasia (AH) in young women, there have been high potential risks of later developed relapse. The aim of this study was whether changes in FDG and fluoroestradiol (FES) PET parameters following hormone treatment have the prognostic factor in prediction of later developed relapse. Methods: Eight young patients with EC and AH were treated by fertility-sparing treatment with a high-dose of medroxyprogesterone acetate (MPA) for 26 weeks. All patients underwent two FDG and FES-PET scans at baseline and 8 weeks after the beginning of MPA treatment, respectively. For each lesion, metabolic indices were calculated by standardized uptake values (SUV). All patients were followed up for 2 years. Values of FDG-SUV, FES-SUV and FES/FDG SUV ratio of tumors were retrospectively reviewed. The correlation between these parameters and clinical outcome of EC and AH for 2 years was evaluated. Results: An initial complete response was achieved in all patients. Two of 5 responders (40%) with AH and one of three (33%) responders with EC later developed (72-88weeks) relapse. One of those three patients underwent hysterectomy due to no response for additional MPA therapy. The tracer uptake of FDG and FES was decrease in all eight patients after 8 weeks. The FES/FDG ratio was increased in all three patients with later developed relapse, but the FES/FDG ratio was decrease in all patients without recurrence for 8 weeks. There was a significant difference of the change in FES/FDG ratio between later developed relapse patients and no relapse patients (0.113 vs -0.392; p = 0.044). Conclusions: This study suggests that an increase in the FES/FDG ratio after 8 weeks fertility-sparing hormone treatment with a high-dose of MPA may be a useful biomarker for predicting later developed relapse in EC and AH in young women.

A prospective study of fertility-sparing treatment with megestrol acetate following hysteroscopic curettage for well-differentiated endometrioid carcinoma and atypical hyperplasia in young women

To investigate the feasibility and efficacy of curettage with hysteroscopy followed by megestrol acetate (MA) for well-differentiated endometrioid carcinoma (EC) confined to the endometrium and for atypical hyperplasia (AH) in young women. Fourteen patients with EC and 12 patients with AH were prospectively enrolled in this study. All of the patients received at least 12 weeks of oral MA (160 mg/day) following thorough curettage with hysteroscopy. The response was assessed histologically every 12 weeks. The primary endpoint was the complete response rate. Adverse events, pregnancy rates and recurrence rates were secondary end points. Twenty-one (80.8 %) patients responded to treatment. The median time to response was 12 weeks. After a median follow-up of 32 months, 6 patients had recurrences. Significantly, more patients with infertility or PCOS experienced recurrence (P = 0.040, P = 0.015). Eight patients attempted to conceive after complete response; two spontaneous conceptions and one normal delivery were achieved. No disease-related or treatment-related deaths were observed. Fertility-sparing treatment with MA following entirely hysteroscopic curettage is effective, demonstrating the least toxicity for rigorously selected young women with well-differentiated EC confined to the endometrium or with AH; however, close follow-up is required for the potential consequences of improper patient selection and a substantial rate of recurrence.

Fertility Preservation via Photodynamic Therapy in Young Patients With Early-Stage Uterine Endometrial Cancer

We evaluated the effectiveness of photodynamic therapy (PDT) as a conservative fertility-sparing treatment in young women with early-stage endometrial cancer. We reviewed the medical records of patients with endometrial cancer who had been treated with PDT. Of the patients with endometrioid adenocarcinoma, we included those younger than 35 years and in whom the lesion was confined to the endometrium. Surface photoillumination with red laser light at a wavelength of 630 nm was applied to the uterine endometrial cavity and endocervical canal of patients 48 hours after an intravenous injection of 2 mg/kg of photosensitizer. Complete response was pathologically defined as the complete disappearance of adenocarcinoma or hyperplastic tissue. Sixteen patients were included in the study. Their mean age was 30.7 years, and the mean body mass index was 24.6 kg/m(2). The mean follow-up period was 78 months. Photodynamic therapy was used in 11 patients as primary treatment and in 5 patients as secondary treatment for recurrence after primary hormonal therapy. Complete remission was observed in 12 (75%) of the 16 patients. Of these 12 patients, 4 experienced recurrence (33%). Two of the 4 patients who experienced recurrence showed complete remission after the next course of PDT, and 1 of the 4 nonresponders also showed complete remission after the second course of PDT. The final response rate was therefore 68%. Of the 7 women who attempted to get pregnant, 4 had 7 successful pregnancies (57%, 4/7), resulting in 6 live births. No tumor-related deaths or PDT-related severe adverse effects were noted. Photodynamic therapy can be an effective conservative treatment method for fertility sparing in young patients with early-stage endometrial adenocarcinoma.

Nano-Encapsulation of Arsenic Trioxide Enhances Efficacy against Murine Lymphoma Model while Minimizing Its Impact on Ovarian Reserve In Vitro and In Vivo

Advances in cancer therapy have increased the rate of survival of young cancer patients; however, female lymphoma patients frequently face a temporary or permanent loss of fertility when treated with traditional cytotoxic agents. The potential loss of fertility is an important concern that can influence treatment decisions for many premenopausal cancer patients. The negative effect of chemotherapeutic agents and treatment protocols to patients’ fertility–referred to as fertotoxicity–are thus an increasingly important cancer survivorship issue. We have developed a novel nanoscale formulation of arsenic trioxide, a potent drug for treatment of hematological malignancies, and demonstrate that it has significantly better activity in a murine lymphoma model than the free drug. In parallel, we have developed a novel in vitro assay of ovarian follicle function that predicts in vivo ovarian toxicity of therapeutic agents. Our results reveal that the nanotherapeutic agent is not only more active against lymphoma, but is fertoprotective, i.e., it is much less deleterious to ovarian function than the parent drug. Thus, our in vitro assay allows rapid evaluation of both established and experimental anticancer drugs on ovarian reserve and can inform the selection of efficacious and fertility-sparing treatment regimens for reproductive-age women diagnosed with cancer.

Fertility sparing treatment in young patients with early endometrial adenocarcinoma

The aim of this study was to evaluate fertility-sparing therapy in young patients with endometrial carcinoma. This prospective study was carried out on 8 patients with clinical and radio-graphic stage IA, well differentiated endometrioid adenocarcinoma of the endometrium in Alzahra hospital, Tabriz, Iran. Treatment comprised high-dose megestrol acetate. Dilatation and curettage was repeated every three months. The mean age of the patients was 30 (SD,3.21) years (range 24-35). Of the 8 patients, 7 (87.5%) achieved complete response. The mean time to response was 6.5 months (range 3-9). Of the complete responders, 3 of 7(42.8%) had recurrence; one patient underwent immediate hysterectomy, and 2 were successfully treated with second-line therapy and both subsequently conceived. Conception occurred in 3 of 7 patients (42.8%), in two more than once, However successful pregnancy occurred only in two patients. One patient developed Concomitant ovarian adenocarcinoma. High dose progestin therapy can be an effective fertility-sparing treatment in young patients with well differentiated stage IA endometrial endometrioid cancer confined to endometrium. However, close follow up is required because of risks of conservative treatment.

Simultaneous early ovarian and endometrial cancer treated conservatively with spontaneous pregnancy

IntroductionYoung cancer patients increasingly request fertility sparing alternatives to their cancer treatments, which they should be offered when allowed so by the risk-benefit balance and after obtaining informed consent.Case presentationHere, we report the case of a 25 year-old nulliparous patient who presented with a synchronous endometrioid ovarian and endometrial carcinoma. She was able to conduct a full-term spontaneous pregnancy after conservative surgical treatment followed by adjuvant chemotherapy and hormonal treatment. Fertility sparing treatment is feasible in selected cases of synchronous ovarian and endometrial cancers. Thorough follow-up remains mandatory.ConclusionThis case demonstrates some interesting and unique features of synchronous ovarian and endometrial cancers since it resulted in a spontaneous pregnancy and normal delivery.

Fertility-Preserving Surgery in Patients with Early Stage Cervical Carcinoma

Fertility preservation is an important issue for patients in reproductive age with early stage cervical cancer. In view of recent developments, our purpose was to review and discuss available surgical alternatives. A literature search was conducted using PUBMED, including papers between 1980 and December 2011. In patients with stage IA1 cervical cancer, conization is a valid alternative. Patients with stage IA2-IB1 disease can be conservatively treated by radical trachelectomy. This is as well-established conservative approach and appears to be safe and effective in allowing a high chance of conception. Prematurity is the most serious issue in pregnancies following trachelectomy. Less invasive options such as simple trachelectomy or conization seem to be feasible for stages IA2-IB1, but more and better evidence is needed. Neoadjuvant therapy might allow conservative surgery to be performed also in patients with more extensive lesions. Ovarian transposition is important when adjuvant radiation is needed. In conclusion, available literature shows that there are interesting fertility-sparing treatment alternatives to the “golden standard” for the management of early cervical cancer in young women.

Safe Fertility-Preserving Management in Endometrial Cancer: Is It Feasible? Review of the Literature

Almost 5% of women with endometrial cancer are under the age of 40, and often have well-differentiated endometrioid estrogen-dependent tumors. Frequently, these women have a strong desire to preserve fertility. Strategies to avoid or reduce the reproductive damage caused by surgery, cytotoxic agents, and radiation are needed. This review addresses options available for safe fertility preservation in endometrial cancer. Clinical treatment with progestin agents may be prescribed after careful evaluation and extensive counseling. Strict criteria should be employed to select suitable patients, using imaging methods and endometrial sampling, once it has been established that standard surgical staging will not be performed. Conservative fertility-sparing treatment should only be offered to patients with a grade 1 well-differentiated tumor, absence of lymph vascular space invasion, no evidence of myometrial invasion, metastatic disease, or suspicious adnexal masses, and strong and diffuse expression of progesterone receptors on immunohistochemistry staining of the endometrial specimen. The presence of co-existing ovarian metastatic of synchronous cancer should be investigated and excluded before the decision to preserve the ovaries. In addition to these conservative therapeutic options, the use of assisted reproductive technology (ART) has made it possible for women with endometrial cancer to give birth to a child without compromising their prognosis. Gamete, embryo, or ovarian tissue cryopreservation techniques can also be employed, although some of these are still considered experimental. Fertility preservation is infrequently applied in the cancer population, and there are scarce good quality studies in the literature, which makes careful staging, thorough counseling, and close follow-up of the patients imperative so as not to jeopardize cancer cure. (J GYNECOL SURG 28:399)

The Clinical Management of Endometrial Cancer in Young Women

Endometrial cancer (EC) remains the leading female genital tract malignancy in industrialized countries. Incidence rates are increasing in many Asia countries. A trend of increased fractions occurring in young women also has been observed. When fertility preservation is not a concern, standard surgical staging and tailored adjuvant therapy regardless of age should be practiced. High remission rates with subsequent pregnancies are seen in clinical stage IA without myometrial invasion and in grade 1 EC of young women using oral high-dose progestins as fertility-sparing treatment (FST), yet high recurrences and synchronous or metachronous ovarian malignancies should be cautioned. Intrauterine progestins seem efficacious but more investigations are needed. Aromatase inhibitors have limited data at present. Current selection criteria have been suboptimal for preserving uterine and/or ovary for young EC patients. Investigations on molecular profiles for selecting candidates for preserving ovary or FST and whether to do a consolidation hysterectomy are necessary.