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Fertility preservation for people with cancer

Ovarian transposition

Clinical Question

Does the use of ovarian transposition, prior to radiation therapy in women with cancer, reduce the risk of primary ovarian insufficiency? Does it reduce the risk of loss of ovarian reserve?

The quality of the evidence supporting ovarian transposition for fertility preservation varies. Most studies of the use of ovarian transposition (OT) for fertility preservation in women with cancer examine ovarian function after treatment for cervical cancer, although OT is relevant to Hodgkins lymphoma and some brain and spinal tumors. There are no randomised controlled trials and very few studies that compare patients who undergo ovarian transposition with patients who don’t. Many studies also use surrogate end-points for ovarian function (FSH levels, vasomotor symptoms and estrogen levels) and we were unable to find any studies that looked at birth rates in this population.

Only one study looked at ovarian function in women with cancer (mostly cervical) after OT compared to cancer patients without OT. They found that ovarian function was significantly better in women who had undergone OT prior to radiation therapy (5 years ovarian function 60.3% after OT versus 0.0% without OT p < 0.001).[1] This study is weakened by its retrospective design, small number of women included and the heterogeneous nature of treatments women received.

Other studies looking at ovarian function in women with cervical cancer after OT and pelvic radiation also found that a proportion of these women retained ovarian function. This proportion varies from 41%[2] and 64%[3] to 83%.[4] None of these studies included a control group. However, a systematic review and meta-analysis of 24 studies of ovarian transposition in women with cancer (majority cervical), found that overall OT is associated with preservation of ovarian function. They also noted the need for more research including non-OT control groups.[5]

Radiotherapy

Radiation to the pelvis contributes to loss of ovarian function, even when OT is performed. Du et al examined women with cervical cancer who had undergone OT and compared three different radiotherapy protocols. They found that limiting radiation dose in some protocols may improve the chance of preserving fertility.[6] Again, this study was limited by the number of women and length of follow-up. A similar study found that 60% of women treated by external radiation therapy experienced ovarian failure, compared to 90% receiving brachytherapy.[4]

The site of ovarian transposition above the iliac crest may determine if the radiotherapy field includes the ovaries. One study found that ovaries transposed to a site more than 1.5 cm from the iliac crest were more likely to retain their function.[7] However, this is contradicted by another study that found transposition of ovaries more than 2 cm above the iliac crest did not completely protect ovaries from the radiation field.[6] Recommendations on radiotherapy and surgical protocols for ovarian transposition are beyond the scope of this guideline.

Risks

Risks from ovarian transposition include ovarian torsion, ovarian cysts and seeding in the transposed ovaries. A systematic review by Gubbala et al found that these risks were low.[5]

Evidence Summary

Evidence summaryLevelReferences
Ovarian transposition prior to radiotherapy to the pelvis may reduce premature ovarian insufficiency in women with cancer, although there is little long-term data or standardisation of transposition procedures amongst studies.III-2[1], [2], [5]


Recommendations

Evidence-based recommendationGrade
Ovarian transposition prior to radiotherapy to the pelvis may preserve ovarian function and may be considered for pre-menopausal women with pelvic cancers wanting to preserve their fertility.C

References

  1. Hoekman EJ, Knoester D, Peters AAW, Jansen FW, de Kroon CD, Hilders CGJM. Ovarian survival after pelvic radiation: transposition until the age of 35 years. Arch Gynecol Obstet 2018 Nov;298(5):1001-1007 Available from: http://www.ncbi.nlm.nih.gov/pubmed/30218184.
  2. Buekers TE, Anderson B, Sorosky JI, Buller RE. Ovarian function after surgical treatment for cervical cancer. Gynecol Oncol 2001 Jan;80(1):85-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11136575.
  3. Pahisa J, Martínez-Román S, Martínez-Zamora MA, Torné A, Caparrós X, Sanjuán A, et al. Laparoscopic ovarian transposition in patients with early cervical cancer. Int J Gynecol Cancer 2008 May;18(3):584-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18476952.
  4. Morice P, Juncker L, Rey A, El-Hassan J, Haie-Meder C, Castaigne D. Ovarian transposition for patients with cervical carcinoma treated by radiosurgical combination. Fertil Steril 2000 Oct;74(4):743-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11020517.
  5. Gubbala K, Laios A, Gallos I, Pathiraja P, Haldar K, Ind T. Outcomes of ovarian transposition in gynaecological cancers; a systematic review and meta-analysis. J Ovarian Res 2014;7:69 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24995040.
  6. Du Z, Qu H. The relationship between ovarian function and ovarian limited dose in radiotherapy postoperation of ovarian transposition in young patients with cervical cancer. Cancer Med 2017 Mar;6(3):508-515 Available from: http://www.ncbi.nlm.nih.gov/pubmed/28211638.
  7. Hwang JH, Yoo HJ, Park SH, Lim MC, Seo SS, Kang S, 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. Fertil Steril 2012 Jun;97(6):1387-93.e1-2 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22464082.

Body of evidence

In female cancer patients does the use of ovarian transposition prior to radiation therapy reduce the risk of primary ovarian insufficiency and loss of ovarian reserve? Does ovarian transposition result in pregnancy and live birth?

CitationLevel of EvidenceQuality of EvidenceSize of EffectNumber of PatientsRelevance of Evidence
Buekers TE, Anderson B, Sorosky JI, Buller RE. Ovarian function after surgical treatment for cervical cancer. Gynecol Oncol 2001 Jan;80(1):85-8 Available from:http://www.ncbi.nlm.nih.gov/pubmed/11136575III-3LowN/A102N/A
Du Z, Qu H. The relationship between ovarian function and ovarian limited dose in radiotherapy postoperation of ovarian transposition in young patients with cervical cancer. Cancer Med 2017 Mar;6(3):508-515 Available from:http://www.ncbi.nlm.nih.gov/pubmed/28211638 III-3Low1862
Gubbala K, Laios A, Gallos I, Pathiraja P, Haldar K, Ind T. Outcomes of ovarian transposition in gynaecological cancers; a systematic review and meta-analysis. J Ovarian Res 2014;7:69 Available from:http://www.ncbi.nlm.nih.gov/pubmed/24995040 III-2Medium14282
Hoekman EJ, Knoester D, Peters AAW, Jansen FW, de Kroon CD, Hilders CGJM. Ovarian survival after pelvic radiation: transposition until the age of 35 years. Arch Gynecol Obstet 2018 Nov;298(5):1001-1007 Available from:http://www.ncbi.nlm.nih.gov/pubmed/30218184 III-2LowN/A56N/A
Hwang JH, Yoo HJ, Park SH, Lim MC, Seo SS, Kang S, 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. Fertil Steril 2012 Jun;97(6):1387-93.e1-2 Available from:http://www.ncbi.nlm.nih.gov/pubmed/22464082 IVLowN/A53N/A
Morice P, Juncker L, Rey A, El-Hassan J, Haie-Meder C, Castaigne D. Ovarian transposition for patients with cervical carcinoma treated by radiosurgical combination. Fertil Steril 2000 Oct;74(4):743-8 Available from:http://www.ncbi.nlm.nih.gov/pubmed/11020517 III-3Medium41042
Pahisa J, Martínez-Román S, Martínez-Zamora MA, Torné A, Caparrós X, Sanjuán A, et al. Laparoscopic ovarian transposition in patients with early cervical cancer. Int J Gynecol Cancer 2008 May;18(3):584-9 Available from:http://www.ncbi.nlm.nih.gov/pubmed/18476952 IVLowN/A28N/A
Shou H, Chen Y, Chen Z, Zhu T, Ni J. Laparoscopic ovarian transposition in young women with cervical squamous cell carcinoma treated by primary pelvic irradiation. Eur J Gynaecol Oncol 2015;36(1):25-9 Available from:http://www.ncbi.nlm.nih.gov/pubmed/25872330 IVLowN/A27N/A
Swift BE, Leung E, Vicus D, Covens A. Laparoscopic ovarian transposition prior to pelvic radiation for gynecologic cancer. Gynecol Oncol Rep 2018 May;24:78-82 Available from:http://www.ncbi.nlm.nih.gov/pubmed/29915802 IVLowN/A10N/A
Yoon A, Lee YY, Park W, Huh SJ, Choi CH, Kim TJ, et al. Correlation between location of transposed ovary and function in cervical cancer patients who underwent radical hysterectomy. Int J Gynecol Cancer 2015 May;25(4):688-93 Available from:http://www.ncbi.nlm.nih.gov/pubmed/25675036 IVLowN/A21N/A
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Cancer Council Australia