Ovarian Function In Young Patients Research Articles

Abstract 6644: Investigating the effect of immune checkpoint inhibitors (ICI) on ovarian function in young patients with melanoma

Abstract Immune related adverse events (irAEs) from immune checkpoint inhibitors (ICIs) are well documented for nearly every organ system, except for the reproductive system. Mouse models have demonstrated that ICIs can decrease ovarian follicular reserve and impair oocyte maturation, which may have implications for fertility (PMID: 36008687). There are no studies investigating the effect of ICIs on fertility in humans. We sought to evaluate ovarian function in women treated with ICIs compared to untreated women by evaluating non-invasive surrogate markers of ovarian reserve, anti-müllerian hormone (AMH) and antral follicle counts (AFC). We enrolled women 18 - 40 years old diagnosed with stage III or IV melanoma. Participants underwent phlebotomy for AMH levels and a pelvic ultrasound to assess AFC. The medical record was retrospectively reviewed to obtain data on patient characteristics, treatments, and outcomes. A total of 14 patients with stage IIIA - IV melanoma participated. Six patients received ICI treatment before AMH and AFC testing while 8 had no prior ICI exposure. The ICI group ages ranged from 22-40 years with a median age of 31 years. The untreated group ages ranged from 25-39 years with a median age of 32 years. The time between starting an ICI and enrolling in the study ranged from 28 - 351 days. ICI regimens included ipilimumab/nivolumab, nivolumab, pembrolizumab, and atezolizumab (on a clinical trial). Four of these six patients experienced an irAE during their course, including: dermatitis, hepatitis, colitis, thyroid dysfunction, and adrenal insufficiency. Median AMH levels were lower for patients treated with ICIs (2.9 vs 4.0 ng/mL), as was median AFC (22.5 vs 23.5 ng/mL). Only three patients’ clinicians discussed fertility preservation. None of the patients underwent fertility preservation. Our study found lower AMH and AFC in women with melanoma who were treated with an ICI compared to untreated women. Although AMH and AFC are surrogate markers for ovarian reserve and fertility, and our study is a small cohort, these early results suggest that ICIs may impact ovarian function. Age is less likely to be a confounding factor as the median age of the treated group was younger than the untreated group. While these results are preliminary, when considered in conjunction with recent pre-clinical data showing changes within the ovaries after ICI treatment, fertility consultation should be considered for young women prior to ICI initiation. We are investigating associations between AMH, AFC, age, ICI exposure, and future pregnancies in an ongoing prospective study. Citation Format: Ashley Hickman, Katherine Smith, Zaraq Khan, Elizabeth Ann Enninga, Yulian Zhao, Elizabeth Cathcart-Rake, Haidong Dong, Lisa Kottschade, Svetomir Markovic, Heather Montane, Anastasios Dimou, Yiyi Yan. Investigating the effect of immune checkpoint inhibitors (ICI) on ovarian function in young patients with melanoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6644.

Gonadotropin-releasing hormone agonist protects ovarian function in young patients with ovarian malignancy undergoing platinum-based chemotherapy: A prospective study.

We aimed to ascertain the effectiveness of gonadotropin-releasing hormone (GnRH) agonist co-therapy for the preservation of ovarian function in patients with ovarian malignancy who underwent unilateral salpingo-oophorectomy and platinum-based chemotherapy. We enrolled 158 patients with ovarian malignancy who underwent fertility preservation surgery and postoperative platinum-based chemotherapy between January 2018 and December 2020. Patients were divided into two groups based on the use of GnRH agonist (GnRHa) during chemotherapy. Two patients withdrew from the study. Laboratory tests (serum follicle-stimulating hormone [FSH], serum luteinizing hormone [LH], and serum anti-Müllerian hormone [AMH]) were performed pre-chemotherapy and one year post-chemotherapy. Data on menstruation resumption, perimenopausal symptoms (modified Kupperman Menopausal Index [KMI]), health-related quality of life (Medical Outcomes Study Short Form-36 [MOS SF-36]), and obstetric outcomes were collected. One year post-chemotherapy, the serum AMH level in the GnRHa group was higher than that in the control group (P<0.001), while the serum FSH and FSH/LH levels in the GnRHa group were lower than those in the control group (P<0.001). The mean period from last chemotherapy to menstrual resumption was 3.86 and 5.78 months in the GnRHa and control groups (P<0.001), respectively. The rate of menstrual resumption post-chemotherapy was 93.5% and 82.3% in the GnRHa and control groups (P<0.05), respectively. GnRHa co-administration during chemotherapy reduced the likelihood of low AMH levels post-chemotherapy and was significant in the multivariate analysis (P<0.05). The modified KMI scores and MOS SF-36 scores were better in the GnRHa group than in the control group (both P<0.001). GnRHa protects ovarian function during platinum-based adjuvant chemotherapy in young patients with ovarian malignancy. This study provides a therapeutic reference for gynecologists, especially for those in economically and medically underdeveloped areas. Chinese Clinical Trial Registry (chiCTR1800019114; October 26, 2018; http://www.chictr.org.cn/index.aspx).

60MO Ovarian function in young patients (pts) treated with postneoadjuvant palbociclib (PAL) and endocrine therapy (ET) for hormone receptor (HR)-positive, HER2-negative early breast cancer (BC): Explorative analysis in Penelope-B

PENELOPE-B is a phase III study investigating the role of PAL + ET vs placebo + ET in HR+, HER2- early BC pts with high risk of relapse after neoadjuvant chemotherapy (NACT). Invasive disease-free survival was not improved with PAL + ET (Loibl JCO 2021). Estradiol (E2), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) values might be influenced by post-NACT PAL. Changes in hormones for pts treated with CDK4/6 inhibitors + ET are not well explored.

Hormone Therapy Use Among Young Patients with Cervical Cancer in Southern Saskatchewan

ObjectiveTreatment for cervical cancer can cause cessation of ovarian function in young patients. Physician counselling practices related to premature menopause and hormonal therapy (HT) for young cervical cancer patients is not well known. The primary objective of this study was to assess the frequency of HT counselling and usage among young cervical cancer patients. The secondary objective was to assess clinical and demographic factors associated with HT use. MethodsThis retrospective review included adult women younger than age 50 years who received treatment for cervical cancer between 2007 and 2017. Patient and disease characteristics, disease outcome, and documentation of HT and bone health counselling were collected from electronic records. Descriptive statistical analysis was performed for the primary objective, and independent t tests and χ2 tests were used for secondary objective data analysis. ResultsIn this study, 67 premenopausal women with cervical cancer (stages I–III) lost ovarian function from cancer treatment, of whom 52% had received counselling on HT from their oncologists. Thirty-nine percent of patients were using HT at the time of their last review. Younger women were more likely than older women to receive HT counselling (mean age 37.3 ± 6.6 y vs. 42.4 ± 6.0 y; P = 0.001). Counselling frequency and usage of HT were not affected by cancer stage, body mass index, or smoking status. ConclusionYoung asymptomatic patients should receive HT if not contraindicated, yet half of qualified cervical cancer patients in this study received counselling on premature menopause and HT. Structured counselling on HT should be implemented as an integral part of cervical cancer care.

Progress of adjuvant therapy after radical resection of early cervical cancer

Radical surgery is the first choice for the treatment of early cervical cancer. Patients need radiotherapy and chemotherapy according to the risk factors.concurrent chemoradiotherapy with cisplatin is recommended according to NCCN recommended guidelines for the treatment of cervical cancer, with any post-operative high risk factors (lymph node metastasis, positive vaginal margin, and para-uterine infiltration). for cervical cancer patients without high risk factors but with moderate risk factors that meet Sedlis criteria, it is recommended to supplement post-operative pelvic external irradiation ± with concurrent chemotherapy with cisplatin.However, these adjuvant treatments can cause radioactive cystitis and proctitis, even vesicovaginal fistula, rectovaginal fistula, long or irreversible adverse reactions, affecting ovarian function in young patients who retain the ovary, which can lead to a decline in the quality of life of patients. These problems make it a hot topic whether chemotherapy can be used in postoperative adjuvant therapy of cervical cancer patients. This article reviews the research progress of adjuvant therapy for early cervical cancer.

Spotlight on triptorelin in the treatment of premenopausal women with early-stage breast cancer.

Endocrine treatment represents the cornerstone of endocrine-sensitive premenopausal early breast cancer. The estrogen blockade plays a leading role in the therapeutic management of hormone receptor-positive breast cancer together with surgery, radiotherapy, and selective antiestrogen treatments. For several years, selective estrogen receptor modulators, such as tamoxifen, have represented the mainstay of therapy. The role of amenorrhea has been extensively elucidated in the past year: the benefit observed with chemotherapy-induced amenorrhea has strengthened its therapeutic role. Luteinizing hormone-releasing hormone (LHRH) has been introduced in oncology practice to induce amenorrhea in order to increase the advantage obtained from endocrine treatment. Triptorelin is one of the most widely used LHRH analogs currently available in clinical practice. It was recently investigated in two major clinical trials that studied the role of complete estrogen blockade in the premenopausal setting. Both showed the clinical benefit due to ovarian suppression treatment, primarily in high-risk patients. Furthermore, triptorelin and other LHRH analogs have recently been investigated in the attempt to preserve the ovarian function in young patients. The medical treatment of early breast cancer is always evolving in the effort to search for safe and efficacious treatments. The role of LHRH analogs is actually well recognized as contributing to the improvement of the medical treatment of premenopausal women with early breast cancer.

Correlation between location of transposed ovary and function in cervical cancer patients who underwent radical hysterectomy.

The study investigated the association between the location of transposed ovaries and posttreatment ovarian function in patients with early cervical cancer (IB1-IIA) who underwent radical hysterectomy and ovarian transposition with or without adjuvant therapies. Retrospective medical records were reviewed to enroll the patients with early cervical cancer who underwent ovarian transposition during radical hysterectomy at Samsung Medical Center between July 1995 and July 2012. Serum follicle-stimulating hormone (FSH) level was used as a surrogate marker for ovarian function. Twenty-one patients were enrolled. The median age and body mass index (BMI) were 31 years (range, 24-39 years) and 21.3 kg/m² (range, 17.7-31.2 kg/m²), respectively. The median serum FSH level after treatment was 7.9 mIU/mL (range, 2.4-143.4 mIU/mL). The median distance from the iliac crest to transposed ovaries on erect plain abdominal x-ray was 0.5 cm (range, -2.7 to 5.2 cm). In multivariate analysis, posttreatment serum FSH levels were significantly associated with the location of transposed ovaries (β = -8.1, P = 0.032), concurrent chemoradiation (CCRT) as an adjuvant therapy (β = 71.08, P = 0.006), and BMI before treatment (underweight: β = -59.93, P = 0.05; overweight: β = -40.62, P = 0.041). Location of transposed ovaries, adjuvant CCRT, and BMI before treatment may be associated with ovarian function after treatment. We suggest that ovaries should be transposed as highly as possible during radical hysterectomy to preserve ovarian function in young patients with early cervical cancer who might be a candidate for adjuvant CCRT and who have low BMI before treatment.

Use of titanium spiral tacks for long-term oophoropexy before pelvic irradiation.

Ovarian transposition before planned pelvic irradiation can preserve ovarian function in young patients with pelvic malignancies. The transposed ovaries are fixed to the posterolateral abdominal wall. We described the use of a titanium spiral tack as a fixation device and compared it with other methods of oophoropexy. Medical and surgical records of all consecutive patients who underwent oophoropexy in our institution between 2007 and 2013 were reviewed. Demographic and clinical data were summarized; follicle-stimulating hormone values, recorded; and imaging scans, reviewed. Oophoropexy was performed in 30 patients: 28 with cervical carcinomas and 2 with pelvic sarcomas. The procedure was done through laparoscopy in 13 patients and through laparotomy in 17. Titanium spiral tack was used for ovarian fixation in 14 patients, Vicryl suturing in 14, and in 2 cases the ovaries were pulled up through a retroperitoneal tunnel and fixed to the peritoneum with sutures. Titanium spiral tack fixation took a few seconds to perform. There were no immediate intraoperative or postoperative complications. Ovarian function was preserved in 15 patients (7/14 with spiral tack, 6/14 with sutures, and in both patients with retroperitoneal tunneling). Postoperative imaging results showed that all ovaries retained their extrapelvic location for a median period of 11.6 months (range, 2.3-63 months). Spiral tack is a simple, reliable method for oophoropexy before pelvic irradiation. Its efficacy is comparable with that of suture fixation, with the added advantage of ultrashort operative time. It is therefore worth considering as an alternative to suturing.

The Role of Robotics in Ovarian Transposition

CONFLICT OF INTEREST: NONE DECLAREDThe preservation of ovarian function in young patients after radical hysterectomy has an important role at the post-oncologic management and preserves life quality. Ovarian transposition is a technique in order to avoid irreversible damage to the ovaries caused by irradiation. The principal surgical ways in the transposition of the ovaries is both through laparotomy and laparoscopy. Recently, the application of the robotic technology on this method seems to be promising. We performed a literature search with terms related to robotic surgery and ovarian transposition in Pubmed and Scopus. Two articles were identified dealing with this technique. Robotic assisted ovarian transposition is presented and the possible advantages and disadvantages of such a technique are discussed.

Laparoscopic ovarian transposition before pelvic radiation in rectal cancer patient: safety and feasibility.

BackgroundInfertility due to pelvic radiation for advanced rectal cancer treatment is a major concern particularly in young patients. Pre-radiation laparoscopic ovarian transposition may offer preservation of ovarian function during the treatment however its use is limited.AimThe study investigates the safety, feasibility and effectiveness of pre-radiation laparoscopic ovarian transposition and its effect on ovarian function in the treatment o locally advanced rectal cancer.MethodsCharts review of all young female patients diagnosed with locally advanced rectal cancer, underwent laparoscopic ovarian transposition, then received preoperative radiotherapy at king Faisal Specialist Hospital and Research Centre between 2003–2007.ResultsDuring the period studied three single patients age between 21–27 years underwent pre-radiation laparoscopic ovarian transposition for advanced rectal cancer. All required pretreatment laparoscopic diversion stoma due to rectal stricture secondary to tumor that was performed at the same time. One patient died of metastatic disease during treatment. The ovarian hormonal levels (FSH and LH) were normal in two patients. One has had normal menstrual period and other had amenorrhoea after 4 months follow-up however her ovarian hormonal level were within normal limits.ConclusionsLaparoscopic ovarian transposition before pelvic radiation in advanced rectal cancer treatment is an effective and feasible way of preservation of ovarian function in young patients at risk of radiotherapy induced ovarian failure. However, this procedure is still under used and it is advisable to discuss and propose it to suitable patients.

Laparoscopic ovarian transposition in patients with early cervical cancer

The aim of this study was to evaluate the feasibility, efficacy, and morbidity of laparoscopic ovarian transposition on the preservation of hormonal function in patients younger than 45 years operated for early cervical cancer. According to risk factors on pathologic evaluation of the specimen, some of them will receive postoperative pelvic radiotherapy. This subset of patients could benefit from taking the ovaries away from the irradiation field in an effort to preserve their functionality. This prospective study included 28 FIGO stage IB1 cervical cancer patients, 45 years old or younger, maintaining menstrual cycles, who were considered suitable for conservation of the ovaries. The ovarian transposition was performed by laparoscopy as a part of the same celio-Schauta operation. Twelve patients underwent adjuvant pelvic radiotherapy. No intraoperative or postoperative morbidity related to the ovarian transposition was observed, and the procedure only entailed a minimum delay of the operative time. There were no cases of ovarian metastasis. At a mean follow-up of 44 months, 63.6% of patients receiving radiotherapy and 93% of those who nonirradiated maintained normal ovarian function. Two patients developed benign ovarian cysts, requiring oophorectomy, but no other long-term adverse effects of the transposition were identified. To the best of our knowledge, this is the largest series of the laparoscopic procedure reported to date in this setting. According to our results, laparoscopic ovarian transposition is a safe and effective procedure for the preservation of ovarian function in young patients with early cervical cancer undergoing adjuvant radiotherapy after surgery.