妇科恶性肿瘤生育力保护与保存临床路径(2025年版)

中国抗癌协会生育力保护专业委员会

中国实用妇科与产科杂志 ›› 2025, Vol. 41 ›› Issue (7) : 723-729.

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中国实用妇科与产科杂志 ›› 2025, Vol. 41 ›› Issue (7) : 723-729. DOI: 10.19538/j.fk2025070112
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妇科恶性肿瘤生育力保护与保存临床路径(2025年版)

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中国抗癌协会生育力保护专业委员会. 妇科恶性肿瘤生育力保护与保存临床路径(2025年版)[J]. 中国实用妇科与产科杂志. 2025, 41(7): 723-729 https://doi.org/10.19538/j.fk2025070112
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参考文献

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Advances in cancer care have led to a growing number of cancer survivors globally. As cancer increasingly affects women and people of reproductive age, more individuals will be experiencing pregnancy after completing cancer treatment. This Best Practice Advice manuscript describes the epidemiology of pregnancy after cancer, recommended clinical evaluation before pregnancy, key components of pregnancy care for cancer survivors, considerations for delivery planning and postpartum care, and suggested steps for future health and prevention.© 2025 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.
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You L, Lv Z, Li C, et al. Worldwide cancer statistics of adolescents and young adults in 2019:a systematic analysis of the Global Burden of Disease Study 2019[J]. ESMO Open, 2021, 6(5):100255. DOI:10.1016/j.esmoop.2021.100255.
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Shnorhavorian M, Harlan LC, Smith AW, et al. Fertility preservation knowledge,counseling,and actions among adolescent and young adult patients with cancer:A population-based study[J]. Cancer, 2015, 121(19):3499-3506. DOI:10.1002/cncr.29328.
The fertility of adolescent and young adult (AYA) patients with cancer can be threatened by treatments, but to the authors' knowledge little is known regarding the extent to which providers discuss this with patients or recommend fertility preservation, or the patient and physician characteristics associated with these interactions.Questionnaires from 459 AYA patients with cancer who were diagnosed between 2007 and 2008 and recruited through 7 US population-based cancer registries were analyzed using sex-specific multivariable models. The authors assessed characteristics associated with not discussing therapy effects on fertility or fertility preservation options, and not making fertility preservation arrangements.Males without a medical oncologist were more likely not to be told that therapy might affect fertility than those with a medical oncologist (male odds ratio [OR], 2.28; 95% confidence interval [95% CI], 1.03-5.00). Individuals without insurance (male OR, 2.91 [95% CI, 1.41-5.91] and female OR, 5.46 [95% CI, 1.59-18.72]); those raising children aged <18 years; and, among males only, those who received treatment posing no or a low fertility risk (OR, 3.39; 95% CI, 1.60-7.16) were more likely not to discuss fertility preservation with providers. Finally, among males, those without a college degree (OR, 1.98; 95% CI, 1.00-3.97), lacking private insurance (OR, 2.97; 95% CI, 1.16-7.63), and raising children aged <18 years (OR, 3.53; 95% CI, 1.63-7.65) were more likely to not make fertility preservation arrangements; too few females had made fertility preservation arrangements for similar analyses to be performed.Discussion and action surrounding fertility preservation for AYA patients with cancer are associated with medical factors, patient socioeconomic data, and child-rearing status. These results highlight the need for insurance coverage for fertility preservation and increased awareness of fertility preservation options.© 2015 American Cancer Society.
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中国抗癌协会宫颈癌专业委员会. 子宫颈癌筛查规范(2025年版)[J]. 中国实用妇科与产科杂志, 2025, 41(3):332-337. DOI:10.19538/j.fk2025030115.
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Li S, Hu T, Lv W, et al. Changes in prevalence and clinical characteristics of cervical cancer in the People's Republic of China:a study of 10,012 cases from a nationwide working group[J]. Oncologist, 2013, 18(10):1101-1107. DOI:10.1634/theoncologist.2013-0123.
Evaluate the changes in prevalence and clinical characteristics of cervical cancer in China.
[6]
Contreras NA, Sabadell J, Verdaguer P, et al. Fertility-sparing approaches in atypical endometrial hyperplasia and endometrial cancer patients:current evidence and future directions[J]. Int J Mol Sci, 2022, 23(5):2531. DOI:10.3390/ijms23052531.
Endometrial cancer (EC) is the fourth most common cancer in women in developed countries. Although it is usually diagnosed in postmenopausal women, its incidence has increased in young women, as well in recent decades, with an estimated rate of 4% in those under 40 years of age. Factors involved in this increase, particularly in resource-rich countries, include delayed childbearing and the rise in obesity. The new molecular classification of EC should help to personalize treatment, through appropriate candidate selection. With the currently available evidence, the use of oral progestin either alone or in combination with other drugs such as metformin, levonorgestrel-releasing intrauterine devices and hysteroscopic resection, seems to be feasible and safe in women with early-stage EC limited to the endometrium. However, there is a lack of high-quality evidence of the efficacy and safety of conservative management in EC. Randomized clinical trials in younger women and obese patients are currently underway.
[7]
Navarria I, Usel M, Rapiti E, et al. Young patients with endometrial cancer:how many could be eligible for fertility-sparing treatment[J]. Gynecol Oncol, 2009, 114(3):448-451. DOI:10.1016/j.ygyno.2009.05.038.
[8]
Peng H, Jiang J, Li L, et al. Mismatch repair deficiency and abnormal p53 expression has significant predictive value for progesterone resistance and endometrial tumorigenesis in patients with endometrial atypical hyperplasia receiving fertility-preserving treatment[J]. Gynecol Oncol, 2024, 186:154-160. DOI:10.1016/j.ygyno.2024.04.013.
This study aimed to evaluate the prognostic ability of mismatch repair deficiency (MMR-d) and abnormal p53 expression (p53abn) in patients with endometrial atypical hyperplasia (EAH) who underwent fertility-preserving treatment.This retrospective study evaluated 51 patients with EAH who underwent fertility-sparing treatment. Endometrial biopsy specimens obtained before hormone therapy were collected and used for immunohistochemical staining for MMR and p53 proteins. Response, relapse, and progression rates were assessed based on age, body mass index, diabetes, polycystic ovary syndrome, reproductive history, MMR status, and p53 status.Overall, 11/51 (21.6%) patients had loss of MMR proteins and 6/51 (11.8%) had p53abn. Patients with MMR-d had lower complete response (CR) rates than those with normal staining patients at 12 months after initial treatment (p = 0.049). Patients with MMR-d had significantly higher relapse rates than those with MMR-p at the 1-year follow-ups after achieving CR (p = 0.035). Moreover, patients with MMR-d had a higher incidence of disease progression at 2, 3, and 4 years after fertility-sparing treatment (p = 0.001, p = 0.01 and p = 0.035, respectively). Patients with p53abn had higher relapse rates than those with p53wt at the 1- and 2-year follow-ups after achieving CR (p = 0.047 and p = 0.036, respectively). Moreover, patients with p53abn had a higher incidence of disease progression at 3 and 4 years after fertility-sparing treatment (p = 0.02 and p = 0.049, respectively).EAH patients with MMR-d and p53abn have a significantly higher risk of disease relapse and progression. Thus, MMR-d and p53abn may be used as predictive biomarkers of progestin resistance and endometrial tumorigenesis in EAH.Copyright © 2024 Elsevier Inc. All rights reserved.
[9]
Rodolakis A, Scambia G, Planchamp F, et al. ESGO/ESHRE/ESGE Guidelines for the fertility-sparing treatment of patients with endometrial carcinoma[J]. Hum Reprod Open, 2023, 2023(1): hoac057. DOI:10.1093/hropen/hoac057.
[10]
Crafton SM, Cohn DE, Llamocca EN, et al. Fertility-sparing surgery and survival among reproductive-age women with epithelial ovarian cancer in 2 cancer registries[J]. Cancer, 2020, 126(6):1217-1224. DOI:10.1002/cncr.32620.
This study examined predictors of fertility-sparing surgery (FSS) among reproductive-age women diagnosed with epithelial ovarian cancer (EOC). In addition, relationships between FSS and survival were assessed in models stratified by tumor characteristics.The Surveillance, Epidemiology, and End Results (SEER) program and the National Cancer Database (NCDB) were queried for women 44 years old or younger with a primary EOC. FSS included unilateral salpingo-oophorectomy and uterine preservation, whereas surgeries including bilateral salpingo-oophorectomy and hysterectomy were categorized as non-FSS. Logistic regression was used to estimate multivariable-adjusted odds ratios and 95% confidence intervals (CIs) for associations between clinical characteristics (eg, age at diagnosis and race) and FSS odds. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for FSS and overall survival in subgroups defined by stage and grade or by stage and histology. Analyses were stratified by database (SEER vs NCDB).This analysis included 9017 women (SEER, n = 3932; NCDB, n = 5085) with EOC diagnosed between the ages of 15 and 44 years. In both cohorts, factors associated with significantly higher FSS odds included a younger age, a more recent ovarian cancer diagnosis, and no adjuvant chemotherapy. FSS was significantly associated with lower overall survival among women with stage II to IV, serous EOC (SEER HR, 1.61; 95% CI, 1.22-2.12). Significant associations between FSS and survival were not observed in other subgroups defined by stage and grade or by stage and histology.FSS appears to be safe for certain women with EOC but was related to poor survival among women with advanced-stage, serous EOC. Confirmatory studies with information on fertility intentions are needed.© 2019 American Cancer Society.
[11]
Hu L, Yang H, Luo H, et al. Age-specific reference ranges and variation of anti-mülerian hormone in healthy Chinese women of reproductive and perimenopausal age:a nationwide population-based prospective multicenter cross-sectional study[J]. Gynecol Endocrinol, 2025, 41(1):2431230. DOI:10.1080/09513590.2024.2431230.
[12]
Dewailly D, Andersen CY, Balen A, et al. The physiology and clinical utility of anti-Mullerian hormone in women[J]. Hum Reprod Update, 2014, 20(3):370-385. DOI:10.1093/humupd/dmt062.
BACKGROUND The measurement of circulating anti-Müllerian hormone (AMH) has been applied to a wide array of clinical applications, mainly based on its ability to reflect the number of antral and pre-antral follicles present in the ovaries. AMH has been suggested to predict the ovarian response to hyperstimulation of the ovaries for IVF and the timing of menopause, and to indicate iatrogenic damage to the ovarian follicle reserve. It has also been proposed as a surrogate for antral follicle count (AFC) in the diagnosis of polycystic ovary syndrome (PCOS). METHODS This paper is a summary of presentations at a European Society of Human Reproduction and Embryology campus workshop on AMH, with literature cited until September 2013. Published peer-reviewed medical literature about AMH was searched through MEDLINE and was subjected to systematic review and critical assessment by the panel of authors. RESULTS Physiologically, recent data confirm that AMH is a follicular gatekeeper limiting follicle growth initiation, and subsequently estradiol production from small antral follicles prior to selection. AMH assays continue to evolve and technical issues remain; the absence of an international standard is a key issue. The dynamics of circulating AMH levels throughout life can be split into several distinct phases, with a peak in the early 20s before a decline to the menopause, with a strong and positive correlation with non-growing follicle recruitment. There is a more complex rise during childhood and adolescence, which is likely to be more reflective of different stages of follicle development. AMH shows limited short-term variability, but the influence of states such as prolonged oral contraceptive use need to be considered in clinical assessment. There are only very limited data on relationships between AMH and natural fertility at different stages of reproductive life, and while it has a relationship to age at menopause the marked variability in this needs further exploration. AMH may be useful in assessing the need for fertility preservation strategies and detecting post-chemotherapy or surgical damage to the ovarian reserve. Long-term follow-up of patients to ascertain fully the value of post-cancer serum AMH in predicting long-term ovarian function is required. There is a linear relationship between AMH and oocyte yield after ovarian stimulation, which is of value in predicting ovarian hyperstimulation. AMH can also identify 'poor responders', but it seems inappropriate at present to withhold IVF purely on this basis. Women with PCOS show markedly raised AMH levels, due to both the increased number of small antral follicles and intrinsic characteristics of those granulosa cells, and this may contribute to anovulation. The value of AMH in the diagnosis of PCOS remains controversial, but it may replace AFC in the future. CONCLUSIONS For the first time in female reproductive biology, it is possible to measure the submerged part of the iceberg of follicle growth, i.e. the intrinsic, so-called 'acyclic' ovarian activity. An international standard for AMH and improved assay validity are urgently needed to maximize the clinical utility of this very promising biomarker of ovarian function in a large array of clinical situations, both in childhood and adulthood.
[13]
Lie Fong S, Visser JA, Welt CK, et al. Serum anti-müllerian hormone levels in healthy females:a nomogram ranging from infancy to adulthood[J]. J Clin Endocrinol Metab, 2012, 97(12):4650-4655. DOI:10.1210/jc.2012-1440.
Anti-müllerian hormone (AMH) is an accurate marker of ovarian reserve. However, sufficiently large sets of normative data from infancy to the end of reproductive life are scarce.This study was an assessment of serum AMH levels in healthy females.In 804 healthy females ranging from infancy until the end of the reproductive period, serum AMH levels were measured with an enzyme-linked immunometric assay. All adults had regular menstrual cycles. The majority was proven fertile and none of them had used oral contraceptive pills prior to study inclusion.In the total cohort, AMH was inversely correlated with age (r = -0.24; P < 0.001). The age at which the maximum AMH value was attained was at 15.8 yr. In girls younger than 15.8 yr, serum AMH and age were positively correlated (r = +0.18; P = 0.007). Thereafter AMH levels remained stable (r = -0.33; P = 0.66), whereas from the age of 25.0 yr onward, an inverse correlation between AMH and age (r = -0.47; P < 0.001) was observed. At any given age, considerable interindividual differences in serum AMH levels were observed.During infancy AMH levels increase, whereas during adolescence, a plateau until the age of 25 yr was observed. From the age of 25 yr onward, serum AMH levels correlate inversely with age, implying that AMH is applicable as a marker of ovarian reserve only in women of 25 yr old and older. Our nomogram may facilitate counseling women on their reproductive potential.
[14]
Practice Committee of the American Society for Reproductive Medicine. Fertility evaluation of infertile women:a committee opinion[J]. Fertil Steril, 2021, 116(5):1255-1265. DOI:10.1016/j.fertnstert.2021.08.038.
[15]
Practice Committee of the American Society for Reproductive Medicine. Testing and interpreting measures of ovarian reserve:a committee opinion[J]. Fertil Steril, 2020, 114(6):1151-1157. DOI:10.1016/j.fertnstert.2020.09.134.
[16]
Sonmezer M, Oktay K. Fertility preservation in young women undergoing breast cancer therapy[J]. Oncologist, 2006, 11(5):422-434. DOI:10.1634/theoncologist.11-5-422.
Breast cancer accounts for one third of all neoplasms seen in reproductive-age women and affects tens of thousands of women each year in that age group. The adjuvant chemotherapy regimens used for the treatment commonly affect fertility and cause premature ovarian failure. There have been recent advances in the field of fertility preservation, which can allow many of these breast cancer survivors to have children in the future. The most established option is embryo cryopreservation; oocyte cryopreservation can be considered in single women. Both of these approaches require approximately 2 weeks of ovarian stimulation beginning with the onset of the patient's menstrual cycle. Thus, it is crucial that these patients are referred to appropriate assisted reproduction centers as soon as they are diagnosed with breast cancer. Recently developed ovarian stimulation protocols using tamoxifen and letrozole can be used to increase the margin of safety in these patients. When and if a breast cancer patient does not have time to undergo ovarian stimulation prior to chemotherapy, ovarian cryopreservation for future autotransplantation can be offered as the last resort. The benefit of ovarian protection by gonadotropin-releasing hormone analogues is unproven and unlikely, and thus this treatment should not be offered as the sole method of fertility preservation.
[17]
Wallace WH, Thomson AB, Kelsey TW. The radiosensitivity of the human oocyte[J]. Hum Reprod, 2003, 18(1):117-121. DOI:10.1093/humrep/deg016.
We determined the best model available for natural follicle decline in healthy women and used this to calculate the radiosensitivity of the human oocyte.Ovarian failure was diagnosed in six patients with a median age of 13.2 years (range 12.5-16.0) who were treated with total body irradiation (14.4 Gy) at 11.5 years of age (4.9-15.1). We previously estimated the dose of radiation required to destroy 50% of the oocytes (LD(50)) to be <4 Gy. This estimate is an oversimplification, because decay represents an instantaneous rate of temporal change based upon the remaining population pool, expressed as a differential equation: dy/dx = -y[0.0595 + 3716/(11780 + y)], with initial value y(0) = 701 200.Solving the differential equation, we have estimated the number of follicles left after irradiation given as sol(51 - s + r), where r equals age at treatment, s equals age at diagnosis of ovarian failure, and 51 years is the average age of menopause. The surviving fraction of oocytes as a percentage is 100 times this value divided by sol(r). The mean surviving fraction for the six cases is 0.66%. We obtain a function, g(z), which decreases in value from 100% at zero dosage to mean value at dosage z = 14.4 Gy. We have g(z) = 10(mx+c), where c = log(10)100 = 2, and m = [log(10)(0.66) - c]/14.4. Solving g(z) = 50 gives an LD(50) of 1.99.Based on new data and a revised mathematical model of natural oocyte decline, we have determined the surviving fraction of oocytes following irradiation and estimate the LD(50) of the human oocyte to be <2 Gy.
[18]
Meacham LR, Burns K, Orwig KE, et al. Standardizing risk assessment for treatment-related gonadal insufficiency and infertility in childhood adolescent and young adult cancer:the pediatric initiative network risk stratification system[J]. J Adolesc Young Adult Oncol, 2020, 9(6):662-666. DOI:10.1089/jayao.2020.0012.
[19]
Hussein RS, Khan Z, Zhao Y. Fertility preservation in women:indications and options for therapy[J]. Mayo Clin Proc, 2020, 95(4):770-783. DOI:10.1016/j.mayocp.2019.10.009.
Fertility preservation (FP) is a vital issue for individuals in either reproductive or prepubescent stage of life when future fertility may be compromised. The objective of any FP intervention is to minimize or eliminate primary disease burden and to ensure maintaining or preserving reproductive health. Fertility potential can be affected by cancer therapy and numerous other factors, including advancing age, metabolic conditions, autoimmune diseases, specific surgical interventions, and sex affirmation procedures. A paradigm shift focusing on quality-of-life issues and long-term survivorship has emerged, especially because of advances in cancer diagnostics and treatment. Several FP techniques have been widely distributed, while others are still in the research stage. In addition, specific procedures and some potentially fertoprotective agents are being developed, aiming to minimize the hazards of gonadal damage caused by cancer therapy and decrease the need for more costly, invasive, and time-consuming FP methods. This review highlights the advances, indications, and options for FP, both experimental and well-established, in females of various age groups. An electronic search in PubMed, Embase, and Google Scholar databases was conducted, including retrospective studies, prospective clinical trials, meta-analyses, original reviews, and online abstracts published up to June 30, 2019. The search terms used included fertility preservation, oncofertility, embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation. The meeting proceedings of the American Society for Reproductive Medicine and the European Society of Human Reproduction and Embryology were also hand searched.Copyright © 2019 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.
[20]
Practice Committee of the American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy:a committee opinion[J]. Fertil Steril, 2019, 112(6):1022-1033. DOI:10.1016/j.fertnstert.2019.09.013.
[21]
Hansen KR, Knowlton NS, Thyer AC, et al. A new model of reproductive aging:the decline in ovarian non-growing follicle number from birth to menopause[J]. Hum Reprod, 2008, 23(3):699-708. DOI:10.1093/humrep/dem408.
[22]
ACOG. Female age-related fertility decline. Committee Opinion No. 589[J]. Fertil Steril, 2014, 101(3):633-634. DOI:10.1016/j.fertnstert.2013.12.032.
The fecundity of women decreases gradually but significantly beginning approximately at age 32 years and decreases more rapidly after age 37 years. Education and enhanced awareness of the effect of age on fertility are essential in counseling the patient who desires pregnancy. Given the anticipated age-related decline in fertility, the increased incidence of disorders that impair fertility, and the higher risk of pregnancy loss, women older than 35 years should receive an expedited evaluation and undergo treatment after 6 months of failed attempts to conceive or earlier, if clinically indicated. In women older than 40 years, more immediate evaluation and treatment are warranted. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
[23]
Mahajan NK. Optimizing advice and approaches for elective fertility preservation[J]. Best Pract Res Clin Obstet Gynaecol, 2025, 99:102591. DOI:10.1016/j.bpobgyn.2025.102591.
[24]
Emrich NLA, Einenkel R, Färber CM, et al. Ovarian tissue cryopreservation for fertility preservation:a two-decade single-center experience with 451 children and adolescents[J]. Reprod Biol Endocrinol, 2025, 23(1):51. DOI:10.1186/s12958-025-01388-x.
Ovarian tissue cryopreservation (OTC) is the only fertility preservation option for premenarcheal girls before gonadotoxic treatment, but is still considered to be experimental in pediatric patients. This study investigated storage behaviors across different age groups to refine counseling approaches for pediatric patients.
[25]
Su HI, Lacchetti C, Letourneau J, et al. Fertility preservation in people with cancer:asco guideline update[J]. J Clin Oncol, 2025, 43(12):1488-1515. DOI:10.1200/JCO-24-02782.
\n ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the\n \n ASCO Guidelines Methodology Manual\n \n. ASCO Guidelines follow the\n \n ASCO Conflict of Interest Policy for Clinical Practice Guidelines\n \n.\n
[26]
Grubliauskaite M, van der Perk MEM, Bos AME, et al. Minimal infiltrative disease identification in cryopreserved ovarian tissue of girls with cancer for future use:a systematic review[J]. Cancers (Basel), 2023, 15(17):4199. DOI:10.3390/cancers15174199.
Background: Ovarian tissue cryopreservation and transplantation are the only available fertility techniques for prepubertal girls with cancer. Though autotransplantation carries a risk of reintroducing malignant cells, it can be avoided by identifying minimal infiltrative disease (MID) within ovarian tissue. Methods: A broad search for peer-reviewed articles in the PubMed database was conducted in accordance with PRISMA guidelines up to March 2023. Search terms included ‘minimal residual disease’, ‘cryopreservation’, ‘ovarian’, ‘cancer’ and synonyms. Results: Out of 542 identified records, 17 were included. Ovarian tissues of at least 115 girls were evaluated and categorized as: hematological malignancies (n = 56; 48.7%), solid tumors (n = 42; 36.5%) and tumors of the central nervous system (n = 17; 14.8%). In ovarian tissue of 25 patients (21.7%), MID was detected using RT-qPCR, FISH or multicolor flow cytometry: 16 of them (64%) being ALL (IgH rearrangements with/without TRG, BCL-ABL1, EA2-PBX1, TEL-AML1 fusion transcripts), 3 (12%) Ewing sarcoma (EWS-FLI1 fusion transcript, EWSR1 rearrangements), 3 (12%) CML (BCR-ABL1 fusion transcript, FLT3) and 3 (12%) AML (leukemia-associated immunophenotypes, BCR-ABL1 fusion transcript) patients. Conclusion: While the majority of malignancies were found to have a low risk of containing malignant cells in ovarian tissue, further studies are needed to ensure safe implementation of future fertility restoration in clinical practice.
[27]
Lambertini M, Moore HCF, Leonard RCF, et al. Gonadotropin-releasing hormone agonists during chemotherapy for preservation of ovarian function and fertility in premenopausal patients with early breast cancer:a systematic review and meta-analysis of individual patient-level data[J]. J Clin Oncol, 2018, 36(19):1981-1990. DOI:10.1200/JCO.2018.78.0858.
Purpose The role of temporary ovarian suppression with gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy as a strategy to preserve ovarian function and fertility in premenopausal women remains controversial. This systematic review and meta-analysis using individual patient-level data was conducted to better assess the efficacy and safety of this strategy in patients with early breast cancer. Methods The trials in which premenopausal women with early breast cancer were randomly assigned to receive (neo)adjuvant chemotherapy alone or with concurrent GnRHa were eligible for inclusion. Primary end points were premature ovarian insufficiency (POI) rate and post-treatment pregnancy rate. Disease-free survival and overall survival were secondary end points. Because each study represents a cluster, statistical analyses were performed using a random effects model. Results A total of 873 patients from five trials were included. POI rate was 14.1% in the GnRHa group and 30.9% in the control group (adjusted odds ratio, 0.38; 95% CI, 0.26 to 0.57; P <.001). A total of 37 (10.3%) patients had at least one post-treatment pregnancy in the GnRHa group and 20 (5.5%) in the control group (incidence rate ratio, 1.83; 95% CI, 1.06 to 3.15; P =.030). No significant differences in disease-free survival (adjusted hazard ratio, 1.01; 95% CI, 0.72 to 1.42; P =.999) and overall survival (adjusted hazard ratio, 0.67; 95% CI, 0.42 to 1.06; P =.083) were observed between groups. Conclusion Our findings provide evidence for the efficacy and safety of temporary ovarian suppression with GnRHa during chemotherapy as an available option to reduce the likelihood of chemotherapy-induced POI and potentially improve future fertility in premenopausal patients with early breast cancer.
[28]
Roberts JE, Benoit J, Foong S, et al. Fertility preservation in patients undergoing gonadotoxic treatments:a Canadian Fertility and Andrology Society clinical practice guideline[J]. Reprod Biomed Online, 2024, 48(5):103767. DOI:10.1016/j.rbmo.2023.103767.
[29]
Bai F, Lu Y, Wu K, et al. Protecting effects of gonadotropin-releasing hormone agonist on chemotherapy-induced ovarian damage in premenopausal breast cancer patients:a systematic review and meta-analysis[J]. Breast Care (Basel), 2017, 12(1):48-52. DOI:10.1159/000454983.
[30]
Munhoz RR, Pereira AA, Sasse AD, et al. Gonadotropin-releasing hormone agonists for ovarian function preservation in premenopausal women undergoing chemotherapy for early-stage breast cancer:a systematic review and meta-analysis[J]. JAMA Oncol, 2016, 2(1):65-73. DOI:10.1001/jamaoncol.2015.3251.
[31]
Dolmans MM, Taylor HS, Rodriguez-Wallberg KA, et al. Utility of gonadotropin-releasing hormone agonists for fertility preservation in women receiving chemotherapy:pros and cons[J]. Fertil Steril, 2020, 114(4):725-738. DOI:10.1016/j.fertnstert.2020.08.011.
[32]
Hwang JH, Yoo HJ, Park SH, et al. Association between the location of transposed ovary and ovarian function in patients with uterine cervical cancer treated with (postoperative or primary) pelvic radiotherapy[J]. Fertil Steril, 2012, 97(6):1387-1393.e932. DOI:10.1016/j.fertnstert.2012.02.052.
To evaluate the effectiveness of ovarian transposition procedures in preserving ovarian function in relation to the location of the transposed ovaries in patients who underwent surgery with or without pelvic radiotherapy.Retrospective.Uterine cancer center.A total of 53 patients with cervical cancer who underwent ovarian transposition between November 2002 and November 2010.Ovarian transposition to the paracolic gutters with or without radical hysterectomy and lymph node dissection.Preservation of ovarian function, which was assessed by patient's symptoms and serum FSH level.Lateral ovarian transposition was performed in 53 patients. Based on receiver operator characteristic curve analysis, optimum cutoff value of location more than 1.5 cm above the iliac crest was significantly associated with preservation of ovarian function after treatment (area under receiver operator characteristic curve: 0.757, 95% confidence interval [CI]: 0.572-0.943). In univariate analysis, higher location of transposed ovary more than 1.5 cm from the iliac crest was the only independent factor for intact ovarian function (odds ratio 9.91, 95% CI: 1.75-56.3). Multivariate analysis confirmed that the location of transposed ovary (odds ratio 11.72, 95% CI 1.64-83.39) was the most important factor for intact ovarian function.Location of transposed ovary higher than 1.5 cm above the iliac crest is recommended to avoid ovarian failure after lateral ovarian transposition after primary or adjuvant pelvic radiotherapy in cervical cancer.Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
[33]
Buonomo B, Multinu F, Casarin J, et al. Ovarian transposition in patients with cervical cancer prior to pelvic radiotherapy:a systematic review[J]. Int J Gynecol Cancer, 2021, 31(3):360-370. DOI:10.1136/ijgc-2020-001774.
[34]
Perri T, Ben-Baruch G, Davidson T, et al. Use of titanium spiral tacks for long-term oophoropexy before pelvic irradiation[J]. Int J Gynecol Cancer, 2014, 24(6):1133-1136. DOI:10.1097/IGC.0000000000000146.
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.
[35]
Morice P, Juncker L, Rey A, et al. Ovarian transposition for patients with cervical carcinoma treated by radiosurgical combination[J]. Fertil Steril, 2000, 74(4):743-748. DOI:10.1016/s0015-0282(00)01500-4.
To assess the indications, effectiveness, and complications of ovarian transposition before pelvic irradiation for cervical cancer.Prospective study.Gynecologic oncology department at a French cancer center.One hundred seven patients treated for cervical cancer.Ovarian transposition to the paracolic gutters with radical hysterectomy and lymphadenectomy.Clinical and laboratory follow-up tests for ovarian function.Bilateral ovarian transposition was achieved in 104 patients (98%). Twelve patients were lost to follow-up or excluded because of evolution of the disease. Preservation of ovarian function was achieved in 83% of the patients having follow-up. The rates of ovarian preservation were 100% for patients treated exclusively by surgery, 90% for patients treated by postoperative vaginal brachytherapy, and 60% for patients treated by postoperative external radiation therapy and vaginal brachytherapy. The main risk for ovarian failure was found in patients treated by external radiation therapy.Ovarian transposition is a safe and effective procedure for preserving ovarian function in patients treated by a radiosurgical combination. This procedure should be performed in patients <40 years of age with a small invasive cervical carcinoma (<3 cm) treated by initial surgery. In such selected cases, the risk of ovarian metastasis is low.
[36]
Schuurman T, Zilver S, Samuels S, et al. Fertility-sparing surgery in gynecologic cancer:a systematic review[J]. Cancers (Basel), 2021, 13(5):1008. DOI:10.3390/cancers13051008.
Fertility-sparing surgery (FSS) is increasingly being offered to women with a gynecological malignancy who wish to preserve fertility. In this systematic review, we evaluate the best evidence currently available on oncological and reproductive outcome after FSS for early stage cervical cancer, epithelial ovarian cancer, and endometrial cancer. An extensive literature search was conducted using the electronic databases Medline (OVID), Embase, and Cochrane Library to identify eligible studies published up to December 2020. In total, 153 studies were included with 7544, 3944, and 1229 patients who underwent FSS for cervical, ovarian, and endometrial cancer, respectively. We assessed the different FSS techniques that are available to preserve fertility, i.e., omitting removal of the uterine body and preserving at least one ovary. Overall, recurrence rates after FSS are reassuring and therefore, these conservative procedures seem oncologically safe in the current selection of patients with low-stage and low-grade disease. However, generalized conclusions should be made with caution due to the methodology of available studies, i.e., mostly retrospective cohort studies with a heterogeneous patient population, inducing selection bias. Moreover, about half of patients do not pursue pregnancy despite FSS and the reasons for these decisions have not yet been well studied. International collaboration will facilitate the collection of solid evidence on FSS and the related decision-making process to optimize patient selection and counseling.
[37]
Morice P, Scambia G, Abu-Rustum NR, et al. Fertility-sparing treatment and follow-up in patients with cervical cancer,ovarian cancer,and borderline ovarian tumours:guidelines from ESGO,ESHRE,and ESGE[J]. Lancet Oncol, 2024, 25(11):e602-e610. DOI:10.1016/S1470-2045(24)00262-6.
[38]
Dargent D, Franzosi F, Ansquer Y, et al. La trachélectomie élargie,risque de rechute plaidoyer pour un protocole de décision partagée[J]. Bull Cancer, 2002, 89(12):1027-1030.
A series of 96 radical trachelectomies performed between April 1987 and May 2002 at Hospital Edouard Herriot in Lyon is reported. One second cancer (bilateral suprarenal glands cancer) and four recurrences were observed. The retrospective unifactorial analysis demonstrated that the maximal tumoral diameter (2 cm or more) and the depth of infiltration (1 cm or more) were the two only significant factors of risk (p = 0.001 et p = 0.002 respectively). Age less than 30 years and presence of lymphovascular spaces involvement were likely to be factors of risk as well but the level of statistical significance was not reached (p = 0.006). Histotype other than squamous, infiltration of the parametrium and infiltration of the vaginal cuff had no prognosis impact. Adjuvant radiotherapy did not seem to lessen the risk. The chances for recurrence were 19% for the patients affected by a tumor 2 cm or more and 25% for the patients affected by a tumor 2 cm or more with a depth of infiltration 1 cm or more. Should these patients be excluded from the indications of radical trachelectomy? The chances for failure do not seem lower if the radical option is chosen rather than the conservative one. The authors play for a shared decision making.
[39]
Šimják P, Cibula D, Pařízek A, et al. Management of pregnancy after fertility-sparing surgery for cervical cancer[J]. Acta Obstet Gynecol Scand, 2020, 99(7):830-838. DOI:10.1111/aogs.13917.
Cervical cancer is increasingly diagnosed in women who have not yet completed their reproductive plans. For women with early‐stage disease (FIGO stage IA1‐IB1), fertility‐sparing procedures, such as conization, trachelectomy or radical trachelectomy, represent the treatments of choice. However, women who undergo repeated conization or trachelectomy represent a challenge for obstetricians because they are at increased risk of infertility, mid‐trimester miscarriage, preterm premature rupture of membranes and preterm delivery. So far, the evidence‐based guidance on the management of these pregnancies is limited. This article reviews the literature discussing pregnancy management in women after fertility‐sparing surgery for early cervical cancer. Although the evidence is limited, certain measures are desirable, including screening and treatment of asymptomatic bacteriuria, screening for cervical incompetence and progressive cervical shortening by transvaginal ultrasonography, and fetal fibronectin testing. Vaginal progesterone supplementation should be primary prevention for all women after trachelectomy. Women with a history of preterm delivery or late miscarriage may benefit from cervical cerclage. Elective delivery by cesarean section in the early‐term period is desirable.
[40]
程文俊. 卵巢恶性肿瘤生育力保存问题[J]. 中国实用妇科与产科杂志, 2024, 40(11):1082-1086.DOI:10.19538/j.fk2024110107.
[41]
Kyrgiou M, Athanasiou A, Kalliala IEJ, et al. Obstetric outcomes after conservative treatment for cervical intraepithelial lesions and early invasive disease[J]. Cochrane Database Syst Rev, 2017, 11(11):CD012847. DOI:10.1002/14651858.CD012847.
[42]
Nitecki R, Floyd J, Lamiman K, et al. Outcomes of the first pregnancy after fertility-sparing surgery for early-stage cervical cancer[J]. Obstet Gynecol, 2021, 138(4):565-573. DOI:10.1097/AOG.0000000000004532.
To evaluate outcomes of the first pregnancy after fertility-sparing surgery in patients with early-stage cervical cancer.We performed a population-based study of women aged 18-45 years with a history of stage I cervical cancer reported to the 2000-2012 California Cancer Registry. Data were linked to the OSHPD (California Office of Statewide Health Planning and Development) birth and discharge data sets. We included patients with cervical cancer who conceived at least 3 months after a fertility-sparing surgery, which included cervical conization or loop electrosurgical excision procedure. Those undergoing trachelectomy were excluded. The primary outcome was preterm birth. Secondary outcomes included growth restriction, neonatal morbidity, stillbirth, cesarean delivery, and severe maternal morbidity. We used propensity scores to match similar women from two groups in a 1:2 ratio of case group participants to control group participants: population individuals without cancer and individuals with cervical cancer (women who delivered before their cervical cancer diagnosis). Wald statistics and logistic regressions were used to evaluate outcomes.Of 4,087 patients with cervical cancer, 118 (2.9%) conceived after fertility-sparing surgery, and 107 met inclusion criteria and were matched to control group participants. Squamous cell carcinoma was the most common histology (63.2%), followed by adenocarcinoma (30.8%). Patients in the case group had higher odds of preterm birth before 37 weeks of gestation compared with both control groups (21.5% vs 9.3%, odds ratio [OR] 2.7, 95% CI 1.4-5.1; 21.5% vs 12.7%, OR 1.9, 95% CI 1.0-3.6), but not preterm birth before 32 weeks. Neonatal morbidity was more common among the patients in the case group relative to those in the cervical cancer control group (15.9% vs 6.9%, OR 2.5, 95% CI 1.2-5.5). There were no differences in rates of growth restriction, stillbirth, cesarean delivery, and maternal morbidity.In a population-based cohort, patients who conceived after surgery for cervical cancer had higher odds of preterm delivery compared with control groups.Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
[43]
Plante M. Vaginal radical trachelectomy:an update[J]. Gynecol Oncol, 2008, 111(2 Suppl):S105-S110. DOI:10.1016/j.ygyno.2008.07.020.
[44]
Peccatori FA, Azim HA, Orecchia R, et al. Cancer, pregnancy and fertility:ESMO Clinical Practice Guidelines for diagnosis,treatment and follow-up[J]. Ann Oncol, 2013, 24(6):vi160-vi170. DOI:10.1093/annonc/mdt199.
[45]
La Marca A, Pati M, Orvieto R, et al. Serum anti-müllerian hormone levels in women with secondary amenorrhea[J]. Fertil Steril, 2006, 85(5):1547-1549. DOI:10.1016/j.fertnstert.2005.10.057.
Anti-müllerian hormone (AMH) appears to regulate follicular growth. The aim of this study was to investigate AMH serum levels in patients affected by secondary amenorrhea. The AMH was significantly lower (or undetectable) in patients with premature ovarian failure (POF) and significantly higher in patients affected by polycystic ovary syndrome (PCOS). We suggest that serum AMH evaluation could be associated with that of established hormones, such as FSH, LH, and E2, when the activity of hypothalamo-pituitary-ovarian axis is investigated.
[46]
盛超, 王志坚. 优化妊娠间隔改善妊娠结局[J]. 中国实用妇科与产科杂志, 2023, 39(6):581-584.DOI:10.19538/j.fk2023060102.

基金

国家重点研发计划“减轻子宫损伤的相关术式优化与技术创新”(2024YFC2707503)
深圳市生殖保存与生育力保护公共服务平台(XMHT20220104049)
深圳市女性生殖健康临床概念验证中心(深科技创新资(2023)78号)

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