|Year : 2018 | Volume
| Issue : 1 | Page : 36-43
Fertility preservation in endometrial carcinoma: Case series of 11 patients
Madhuri Patil1, Nalini Mahajan2
1 Dr. Patil's Fertility and Endoscopy Clinic, Bengaluru, India
2 Department of Reproductive Medicine, Mother and Child Hospital, New Delhi, India
|Date of Web Publication||13-Feb-2018|
Dr. Patil's Fertility and Endoscopy Clinic, No. 1 Uma Admiralty, First Floor, Bengaluru - 560 029, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: Endometrial cancer comprises 7.1% of all new cancer cases in females. Carcinoma of the endometrium is one of the long-term complications of polycystic ovarian syndrome (PCOS) due to unopposed estrogen action due to chronic anovulation. The standard treatment involves hysterectomy and bilateral salpingo-oophorectomy, due to its hormonal sensitivity. In endometrial cancer without infiltration to the myometrium and no extrauterine involvement, conservative treatment can be offered to women who wish to preserve fertility.
Results: We report 11 cases of endometrial carcinoma either diagnosed during workup for infertility or referred for fertility preservation (FP) before definitive treatment. About 72.7% (7/11) of patients had PCOS, it becomes important for clinicians to suspect and rule out endometrial carcinoma by regular endometrial surveillance which, includes transvaginal ultrasound and/or endometrial biopsy in all PCOS women who have abnormal uterine bleeding, prolonged amenorrhea, unopposed estrogen exposure, and thick endometrium especially on day 3 of the menstrual cycle. About 36.36% (4/11) of our patients were not convinced for FP and were either lost to follow-up or underwent definitive therapy. Thus, it is important that all patients with endometrial carcinoma should be counseled not only by the oncologist but also by a reproductive endocrinologist and a psychosocial counselor, both together and separately. This will enable the patient to make a right choice of the treatment modality.
Conclusion: Conservative treatment with progestogen therapy in selected young patients with well-differentiated carcinoma limited to the endometrium helps in preserving fertility. If they fail to conceive in the first attempt of in vitro fertilization, it is mandatory to monitor them for recurrence till a definitive treatment is planned. If definitive treatment is required fertility can be preserved either by oocyte or embryo freezing. Some women with low risk of ovarian involvement can benefit by ovarian tissue cryopreservation.
Keywords: Assisted reproductive technology, cancer, cryopreservation, fertility preservation, infertility, ovarian tissue
|How to cite this article:|
Patil M, Mahajan N. Fertility preservation in endometrial carcinoma: Case series of 11 patients. Onco Fertil J 2018;1:36-43
| Introduction|| |
Endometrial cancer comprises 7.1% of all new cancer cases in females. It has a incidence rate of 12.9/100,000 women. It is the third most common cause of gynecologic cancer death, with a mortality rate of 2.4/100,000. It is also a long-term complications of polycystic ovarian syndrome (PCOS) due to unopposed estrogen action due to chronic anovulation. Moreover, it has been observed in some ovulatory PCOS women or those receiving exogenous progestin the secretory endometrium exhibits progesterone resistance accompanied by dysregulation of gene expression controlling steroid action and cell proliferation. The standard treatment involves hysterectomy and bilateral salpingo-oophorectomy, due to its hormonal sensitivity. In endometrial cancer without infiltration to the myometrium and no extrauterine involvement, conservative treatment can be offered to women who wish to preserve fertility.
We report 11 cases of endometrial carcinoma either diagnosed during workup for infertility or referred for fertility preservation (FP) before definitive treatment.
| Case Reports|| |
A 32 year old case presented with subfertility for 2½ years. She was a case of PCOS with irregular cycles with a history of hypothyroidism, diabetes, abnormal lipid profile, anemia and immune thrombocytopenic purpura. Hysterosalpingography showed patent tubes with endometrial polyp. She underwent two cycles of ovulation induction with gonadotropins and intrauterine insemination (IUI) but failed to conceive. She was therefore advised hysteroscopy in view of hyperplastic endometrium. At hysteroscopy, the endometrium was polypoidal and hyperplastic, and the histopathology report was endometrial carcinoma (endometrioid adenocarcinoma, International Federation of Gynecology and Obstetrics Grade II of III) [Figure 1]a and [Figure 1]b.
|Figure 1: (a) Hysteroscopy picture; (b) adenocarcinoma of the endometrium|
Click here to view
She was treated with tablet megesterol acetate 160 mg for 3 months. At follow-up after 3 months, she had ammenorrhea, but still her endometrium was 10.6 mm. Diabetes was uncontrolled with glycosylated hemoglobin of 8.6 and fasting blood sugar of 136 mg. Her repeat biopsy showed well-differentiated endometrioid adenocarcinoma with focal progesterone response. Megestrol acetate 160 mg daily was continued further for 45 days following which she was again re-evaluated. After 45 days, when she came for follow-up, her transvaginal ultrasound showed both ovaries to have multiple small follicles with fluid in endometrial cavity and endometrial polyps projecting into the cavity [Figure 2].
Magnetic resonance imaging (MRI) was advised which revealed focal irregularity of endometrium limited to junctional zone without the involvement of myometrium. No lymph nodes involvement was noted. Repeat Endometrial Biopsy (EB) showed no evidence of malignancy, so the decision was taken to start stimulation for in vitro fertilization (IVF) [Figure 3].
Following a negative biopsy, she underwent 2 cycles of IVF but failed to conceive. In both cycles, her oocyte quality was poor with poor embryogenesis. Most oocytes had debris in large perivitelline space with dark cytoplasm and fractured polar body. After the failure of IVF she has not come for follow-up despite repeated reminders, so her endometrial status is not known.
A 34 year old PCOS woman was diagnosed with endometrial carcinoma when laparoscopy was done for ovarian drilling and assessment of the pelvic factor for infertility [Figure 4]a and [Figure 4]b.
|Figure 4: (a) Hysteroscopic view (b) histopathology depicting adenocarcinoma|
Click here to view
Treated medically with medroxyprogesterone 400 mg daily for 3 months. Repeat endometrial biopsy showed endometrium in proliferative phase with simple hyperplasia at histopathological examination. The patient underwent 4 cycles of ovulation induction with timed intercourse. As there was no conception, she underwent 3 cycles of ovulation induction with IUI. Despite the use of gonadotropins for ovulation induction, she had persistent thin endometrium during the IUI cycles. As she did not conceive, she was referred to our assisted reproductive treatments (ART) center for further management. Repeat biopsy showed simple hyperplasia and a small focus of complex hyperplasia without atypia. Areas of squamous metaplasia were also noted. Oncologist's opinion sought, and decision was taken to start stimulation for IVF. Conceived in thefirst IVF cycle and has a 14 weeks ongoing pregnancy.
A 32 year old married for 4 years with PCOS and male factor (oligoasthenospermia) was for intracytoplasmic sperm injection as she had 2 failed IUI cycles. At pre-ART hysteroscopy, [Figure 5] endometrium had multiple polyps with shaggy looking endometrium at places. Endometrial carcinoma was diagnosed at biopsy. She was advised medical treatment, but she refused to accept that she had cancer and went for alternative methods of medicine (Ayurveda) and was lost to follow-up.
A 30 year old patient married for 7 years came for infertility treatment. She was a case of PCOS and diagnosed with endometrial carcinoma 6 months after marriage. She has taken progesterone for 4 years as repeat biopsies were positive. Her positron emission tomography scans were done regularly to rule of extension of the disease. In February 2015, when the endometrial biopsy showed only hyperplasia, and there was no evidence of carcinoma she had undergone an IVF cycle where 2 fresh embryos were transferred and 2 fresh embryos were frozen. She did not conceive both in the fresh as well as frozen embryo transfer (FET) cycle. For the past 15 months, she has not taken any treatment and is regularly following up with transvaginal ultrasound. As she did not conceive in the earlier two IVF cycle done elsewhere, she came to us for opinion and further treatment. At transvaginal ultrasound, she had thick and irregular endometrium [Figure 6] and so was advised repeat biopsy, which was again positive.
She has been advised IVF with cryopreservation of embryos followed by definitive treatment. The patient was unwilling for IVF with cryopreservation of embryos and definitive treatment and now has got progesterone intrauterine device (IUD) inserted with her Oncologist.
A 34 year old women married for 6 years with primary infertility and PCOS, was diagnosed to have well-differentiated endometriod adenocarcinoma (estrogen receptor +, progesterone receptor +, and P53 – focal high) at the age of 29 years and was treated with medroxyprogesterone acetate (MPA) for 3 months. She is a known case of epilepsy on treatment. Repeat biopsy a year later was normal. At the age of 33 years, she had undergone hysteroscopic polypectomy with endometrial biopsy, which at histopathology showed complex hyperplasia with no evidence of malignancy. She was given two cycles of oral contraceptive pills after which she underwent 6 cycles of ovulation induction with IUI (2 cycles with gonadotropins). In those six cycles, she failed to conceive and so was then referred to our center. Endometrial biopsy was repeated, and histopathology report showed simple hyperplasia without atypia. She underwent IVF and with the transfer of two blastocyst 4 AA in the fresh cycle. Pregnancy confirmed by rising beta human chorionic gonadotrophin and ultrasound [Figure 7]. She delivered 8 months ago a live male baby by cesarean section at term.
A 30 year old women married for 6 years with primary infertility, diagnosed with endometrial carcinoma during infertility treatment. She took megestrol acetate 160 mg daily for 4 months and after completion of treatment tried to conceive naturally for 3 months but failed. Underwent one cycle of IVF, with the transfer of 2 embryos, but failed to conceive. She then underwent a second IVF with cryopreservation of embryos. She had two embryos [Figure 8] transferred in the surrogate and has a live baby. Husband insisted on definitive treatment for endometrial carcinoma, but she waited for the birth of her baby before undergoing hysterectomy with bilateral salpingo-oophorectomy. Was on regular follow-up for the entire period.
A 27 years old patient with primary infertility for 5 years was diagnosed with endometrial carcinoma at diagnostic hysterolaparoscopy done for infertility [Figure 9].
Treated medically with megestrol acetate 160 mg daily for 3 months after which she underwent IVF. Embryo transfer deferred in view of thin endometrium [Figure 10]. FET was done in a natural cycle and has delivered a female baby by cesarean section. She is under regular surveillance for follow-up.
A 32 years old, case of PCOS with primary infertility 8 years. When investigated for infertility was found to have complex hyperplasia. She was advised treatment but went for a repeat biopsy elsewhere. Here, the endometrial biopsy showed simple hyperplasia and so underwent 4 cycles of IUI followed by 1 cycle of IVF which failed. The patient was erratic with her follow-up. Came for IVF with embryo cryopreservation. On reevaluation by MRI, [Figure 11] repeat hysteroscopy and endometrial biopsy showed endometrial carcinoma again [Figure 12]a and [Figure 12]b. She was lost for follow-up thereafter.
|Figure 12: (a) Hysteroscopy with polypoidal appearance (b) histopathology appearance|
Click here to view
A 23 year old unmarried woman with PCOS was seen for dysfunctional uterine bleeding. Endometrial biopsy showed endometrial carcinoma. After medical treatment, she underwent oocyte freezing for FP [Figure 13]. She is regular in her follow-up and till date has not had a recurrence.
A 33 year old patient with primary infertility for 7 years, diagnosed with endometrial carcinoma. Underwent stimulation with cryopreservation of 2 embryos before definitive treatment. As at MRI there was no extension to the myometrium, the oncologist was requested to preserve the ovaries for further stimulation and cryopreservation of embryos. However, hysterectomy with bilateral salpingo-oophorectomy was done. She has only 2 embryos cryopreserved and is for surrogacy.
A 30 years old woman, married for 6 months, and a known case of PCOS. At the age of 26 years, she had an episode of deep vein thrombosis with pulmonary thromboembolism. She was on low molecular weight heparin since then. After the episode of deep vein thrombosis, she was tested for antiphospholipid antibodies which was reported positive. She had abnormal uterine bleeding (AUB) - polymenorrhea followed by menorrhagia for 3 months 2 years after the diagnosis of deep vein thrombosis for which she was evaluated. At hysteroscopy, the endometrium was hyperplastic and polypoidal [Figure 14].
Adenocarcinoma of the endometrium stage 1 Grade 2 was diagnosed on histopathology. She consulted an Oncosurgeon at a cancer hospital and was advised total abdominal hysterectomy with bilateral salpingo-oophorectomy. She was referred for an opinion to our clinic where she was counseled for conservative management, which included either medical management (tablet megestrol) or IVF with cryopreservation of embryos. The advantages and disadvantages of both the procedures were explained to her. As she was advised definitive treatment by the oncosurgeon, she was not convinced for FP by either of the procedures. She has undergone hysterectomy with bilateral salpingo-oophorectomy.
| Discussion|| |
One-fourth of the cases of endometrial cancer are diagnosed during the reproductive age.
Primary progesterone therapy sometimes can be combined with local surgical excision, has been used as conservative treatment in early well-differentiated tumors to preserve fertility. With conservative treatment, a mean of 72% of the women has complete remission with 23% relapse rate later on. FP in women of endometrial cancer is important because 28% of complete responders subsequently conceived with or without ART. The 3, 6, 12, 18, and 24 months' remission probabilities based on the Kaplan–Meier curve were 30.4%, 72.4%, 78.0%, 80%, and 81.4%, respectively. The 4, 6, 12, 18, and 24 months recurrence probabilities based on the Kaplan–Meier curve were 3.6%, 9.6%, 17.2%, 26.0%, and 29.2%, respectively. Pregnancy rates reported vary from 32% to 100% in patients attempting to conceive. Pregnancy rate reported was 31.6% of these 54.1% were obtained with ART, and 26.1% of pregnancies were spontaneous. In India, the incidence of endometrial cancer is 4.3/100,000 women.
There is considerable evidence that reproductive factors such as polycystic syndrome play an important role in etiology of endometrial carcinoma. Anovulation in the adolescent and reproductive age which include the unmarried and nulliparous women is associated with increased risk of endometrial cancer along with a positive association between infertility and endometrial cancer in young women.
FP is one of the major concerns in young women with endometrial cancer and should be tailored according to patient's age, stage of disease, involvement of myometrium, or extrauterine involvement detected by transvaginal ultrasonography and computed tomography, contrast-enhanced MRI. MRI has the highest sensitivity and specificity (88% and 85%, respectively) to detection of spread. The other factors that determine the method of FP are treatment planned, time available before treatment, whether she has a partner or not. It also depends on whether the women is highly motivated to maintain her reproductive potential, is fully comprehend and is willing to accept the risks associated with deviation from the standard of care and agreeable to a close follow-up schedule.
Conservative modalities include progestin therapy which includes:
- MPA given orally in the dose of 400–800 mg/day in three divided doses as an initial treatment for 3 months
- Megestrol acetate 160 mg given orally daily and is the preferred treatment as it is associated with a better remission probability and a lower progression rate
- Levonorgestrel-releasing IUD.
After 3 months of treatment, if the disease has regressed patient can be allowed to conceive spontaneously or ART is performed. If there is no regression, additional oral MPA or megestrol is given for further 45–60 days. The treatment period should not exceed 12 months as remission probability does not increase after 12 months of treatment.
Photodynamic therapy and hysteroscopic endometrial carcinoma excision have recently been reported as alternative approaches to progestin therapy alone; however, limited efficacy and safety data exist.,,,
Women subjected to conservative therapy should undergo regular follow-up, as 50% of cases can relapse. In Standard conservative treatment, it is mandatory to monitor for recurrence by hysteroscopic examinations every 3rd month and endometrial sampling should be to be done. It has been observed that obese and anovulatory patients tend to be more resistant to treatment and require a longer duration of treatment.,
In women free of disease, pregnancy should be achieved within the shortest period and ART may have a place in reducing time to conception, thus reducing the time for risk of recurrence. However, ovarian stimulation can be an issue because of the supraphysiological estrogen levels which may stimulate tumor proliferation. Addition of letrozole helps in reducing estradiol levels in these women without compromising the oocyte or embryo quality. Whenever the desired family size has been reached, patients should undergo hysterectomy and bilateral salpingo-oophorectomy because of the persistent relapse risk.
If no remission is observed during conservative management radical surgery with FP methods [Figure 15] should be considered.
When freezing oocytes and embryos, it is important to follow the selection criteria for cryopreservation. It is also important to check for ovarian involvement before selecting the patient for FP. Pretreatment evaluation should include assessment for inherited gynecologic cancer syndromes such as Lynch syndrome. It is very important to counsel the women that a negative genetic evaluation does not exclude the risk of a synchronous or metachronous ovarian malignancy. Surrogacy and uterine transplant are options after radical surgery for endometrial carcinoma.
[Figure 16] shows the overview of conservative management and FP options.
|Figure 16: Algorithm for options of conservative treatment and fertility preservation|
Click here to view
Safety after fertility preservation
Several groups have described the feasibility and safety of fertility-sparing hormone therapy for early-stage endometrial carcinoma ,,,,,,, No detectable increased risk of disease recurrence was associated with most FP methods and pregnancy, even in hormonally sensitive tumors. Cancer treatment has mutagenic effects on the oocyte present in growing follicles and risk is related to the stage of oocyte development during exposure and the drug regimen used., In a study by Park et al. it was concluded that use of ART was associated with significantly higher pregnancy and live birth rates compared with women who attempted spontaneous conception (pregnancy rates: 86.4% vs. 50%, P = 0.001; live birth rates: 70.5% vs. 42.3%, P = 0.020). Cancer therapy or FP does not increase the risk of cancer, chromosomal abnormalities, congenital abnormalities, or fetal malformations in the offspring if conception occurs more than a year after cessation of the treatment.,
| Conclusion|| |
Conservative treatment with progestogen therapy in selected young patients with well-differentiated carcinoma limited to the endometrium helps in preserving fertility and does not seem to worsen the prognosis. Feasibility and safety of fertility-sparing endometrial carcinoma management need to be assessed and patient thoroughly counseled on the oncologic risks. MRI which is the currently the most sensitive imaging modality can confirm that tumor is confined to the endometrial layer only and there is no evidence of myometrial and lymph node involvement or extrauterine spread.
Whenever the desired family size has been reached, patients should undergo hysterectomy and bilateral salpingo-oophorectomy to prevent relapse.
Conservative management of well-differentiated endometrial carcinoma in young patients, combined with assisted reproductive technologies, if needed, does not seem to worsen the prognosis. This approach also provides the possibility of conceiving and carrying a normal pregnancy. Ideal medical treatment regimen is yet to be determined, and recent data suggest that megestrol acetate may be associated with a higher risk of recurrence as compared with MPA. The choice of progestin, dose, and route of administration should be individualized to minimize risks such as thrombophlebitis, weight gain, headaches, sleep disorders, mood and libido changes.
The most important conclusion from our case series is that the patient with endometrial carcinoma should be counseled not only by the oncologist but also by a reproductive endocrinologist and a psycho-social counselor, both together and separately. This will enable the patient to make a right choice of the treatment modality. Moreover, 72.7% (7/11) of patients had PCOS, which makes it mandatory for every clinicians to suspect and rule out endometrial carcinoma by regular endometrial surveillance which includes transvaginal ultrasound and/or endometrial biopsy in all PCOS women who have AUB, prolonged amenorrhea, unopposed estrogen exposure, and thick endometrium especially on day 3 of the menstrual cycle.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, et al.
Global cancer statistics. CA Cancer J Clin 2011;61:69-90.
Dumesic DA, Lobo RA. Cancer risk and PCOS. Steroids 2013;78:782-5.
Koskas M, Uzan J, Luton D, Rouzier R, Daraï E. Prognostic factors of oncologic and reproductive outcomes in fertility-sparing management of endometrial atypical hyperplasia and adenocarcinoma: Systematic review and meta-analysis. Fertil Steril 2014;101:785-94.
La Vecchia C, Franceschi S, Decarli A, Gallus G, Tognoni G. Risk factors for endometrial cancer at different ages. J Natl Cancer Inst 1984;73:667-71.
Balasubramaniam G, Sushama S, Rasika B, Mahantshetty U. Hospital-based study of endometrial cancer survival in Mumbai, India. Asian Pac J Cancer Prev 2013;14:977-80.
Kinkel K, Kaji Y, Yu KK, Segal MR, Lu Y, Powell CB, et al.
Radiologic staging in patients with endometrial cancer: A meta-analysis. Radiology 1999;212:711-8.
Godoy H, Vaddadi P, Cooper M, Frederick PJ, Odunsi K, Lele S, et al.
Photodynamic therapy effectively palliates gynecologic malignancies. Eur J Gynaecol Oncol 2013;34:300-2.
Parazzini F, La Vecchia C, Bocciolone L, Franceschi S. The epidemiology of endometrial cancer. Gynecol Oncol 1991;41:1-6.
Laurelli G, Di Vagno G, Scaffa C, Losito S, Del Giudice M, Greggi S, et al.
Conservative treatment of early endometrial cancer: Preliminary results of a pilot study. Gynecol Oncol 2011;120:43-6.
Mazzon I, Corrado G, Masciullo V, Morricone D, Ferrandina G, Scambia G, et al.
Conservative surgical management of stage IA endometrial carcinoma for fertility preservation. Fertil Steril 2010;93:1286-9.
Gunderson CC, Fader AN, Carson KA, Bristow RE. Oncologic and reproductive outcomes with progestin therapy in women with endometrial hyperplasia and grade 1 adenocarcinoma: A systematic review. Gynecol Oncol 2012;125:477-82.
Penner KR, Dorigo O, Aoyama C, Ostrzega N, Balzer BL, Rao J, et al.
Predictors of resolution of complex atypical hyperplasia or grade 1 endometrial adenocarcinoma in premenopausal women treated with progestin therapy. Gynecol Oncol 2012;124:542-8.
Park JY, Kim DY, Kim JH, Kim YM, Kim KR, Kim YT, et al.
Long-term oncologic outcomes after fertility-sparing management using oral progestin for young women with endometrial cancer (KGOG 2002). Eur J Cancer 2013;49:868-74.
Niwa K, Tagami K, Lian Z, Onogi K, Mori H, Tamaya T, et al.
Outcome of fertility-preserving treatment in young women with endometrial carcinomas. BJOG 2005;112:317-20.
Mazzon I, Corrado G, Morricone D, Scambia G. Reproductive preservation for treatment of stage IA endometrial cancer in a young woman: Hysteroscopic resection. Int J Gynecol Cancer 2005;15:974-8.
Bakkum-Gamez J, Kalogera E, Keeney G, Mariani A, Podratz K, Dowdy S. Conservative management of atypical hyperplasia and grade I endometrial carcinoma: Review of the literature and presentation of a series. J Gynecol Surg 2012;28:262-9.
Gotlieb WH, Beiner ME, Shalmon B, Korach Y, Segal Y, Zmira N, et al.
Outcome of fertility-sparing treatment with progestins in young patients with endometrial cancer. Obstet Gynecol 2003;102:718-25.
Jobo T, Imai M, Kawaguchi M, Kenmochi M, Kuramoto H. Successful conservative treatment of endometrial carcinoma permitting subsequent pregnancy: Report of two cases. Eur J Gynaecol Oncol 2000;21:119-22.
Kaku T, Yoshikawa H, Tsuda H, Sakamoto A, Fukunaga M, Kuwabara Y, et al.
Conservative therapy for adenocarcinoma and atypical endometrial hyperplasia of the endometrium in young women: Central pathologic review and treatment outcome. Cancer Lett 2001;167:39-48.
Kim YB, Holschneider CH, Ghosh K, Nieberg RK, Montz FJ. Progestin alone as primary treatment of endometrial carcinoma in premenopausal women. Report of seven cases and review of the literature. Cancer 1997;79:320-7.
Ramirez PT, Frumovitz M, Bodurka DC, Sun CC, Levenback C. Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: A literature review. Gynecol Oncol 2004;95:133-8.
Randall TC, Kurman RJ. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol 1997;90:434-40.
Meirow D, Levron J, Eldar-Geva T, Hardan I, Fridman E, Zalel Y, et al.
Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N
Engl J Med 2005;353:318-21.
Park JY, Seong SJ, Kim TJ, Kim JW, Kim SM, Bae DS, et al.
Pregnancy outcomes after fertility-sparing management in young women with early endometrial cancer. Obstet Gynecol 2013;121:136-42.
Stensheim H, Cvancarova M, Møller B, Fosså SD. Pregnancy after adolescent and adult cancer: A population-based matched cohort study. Int J Cancer 2011;129:1225-36.
Mueller BA, Chow EJ, Kamineni A, Daling JR, Fraser A, Wiggins CL, et al.
Pregnancy outcomes in female childhood and adolescent cancer survivors: A linked cancer-birth registry analysis. Arch Pediatr Adolesc Med 2009;163:879-86.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10], [Figure 11], [Figure 12], [Figure 13], [Figure 14], [Figure 15], [Figure 16]