21. Cervical carcinoma during pregnancy – Cervical Carcinoma
Major changes in the chapter on cervical carcinoma during pregnancy
This chapter has been completely revised and transferred from a previous subsection into a separate chapter. No recommendations have changed. The literature has been comprehensively supplemented and updated.
P. Wimberger, F.A. Stübs, M.W. Beckmann, M.C. Koch
Approximately 4500 new cases of cervical carcinoma occur in Germany annually, with around one-quarter of the cases being in patients under the age of 35, so that there is a risk of cervical carcinoma in pregnancy [796]. The reported incidence of cervical carcinoma in pregnancy is low, ranging from 0.02% to 0.9% [797].
A distinction needs to be made between an initial diagnosis of cervical carcinoma before pregnancy, but in women who wish to have children, and an initial diagnosis of cervical carcinoma when pregnancy is already present. In this chapter, only the procedure for a first diagnosis of cervical carcinoma and simultaneous pregnancy is discussed. The data situation for an early cervical carcinoma outside of pregnancy with a desire to have children later, involving fertility-preserving procedures, is discussed in Chapter 20.
21.1 Diagnosis of high-grade dysplasia and invasive cervical carcinoma during pregnancy
During pregnancy the portio changes due to physiological hormonal influences. The cervix shows a strong increase in size towards the end of pregnancy and the transformation zone becomes more visible due to eversion of the endometrium. This allows for better visual assessment but can be confused with neoplastic changes [798]. Regardless, if pregnancy is detected, a cytological check is recommended as part of the maternity guideline.
Often cervical carcinoma in pregnant women is asymptomatic, but when symptoms do occur, they include fetid yellowish fluoride or contact bleeding. In advanced stages (≥ FIGO stage IIB), symptoms such as urinary retention and constipation may occur [798].
During pregnancy, any cytological suspicion of higher-grade dysplasia or carcinoma shall be clarified using colposcopy and biopsy.
- Recommendation grade
- A: Starke Empfehlung für oder gegen ein Maßnahme - verwendete Ausdrucksweise = soll/soll nicht
- Level of evidence
- 2+
- References
- [799]
A Pap smear is obligatory during prenatal care. The validity of cytology during pregnancy is the same as outside of pregnancy. Women who do not otherwise take part regularly in cancer screening can thus be reached during pregnancy in particular. It is important to note the pregnancy on the cytology request, so that the cytologist does not misinterpret the physiological changes in the epithelium [800].
Abnormal Pap smears must be clarified using colposcopy (with a targeted biopsy if appropriate) [799]. The sensitivity and specificity of targeted biopsies during pregnancy are 83.7% and 95.9%, respectively [800]. Complications such as secondary bleeding (1–3%), premature delivery, and rupture of the amniotic membranes are very rare [800].
Conizations are only indicated starting in the second trimester of pregnancy when there is colposcopic or macroscopic suspicion of invasion. Reported risks here include a 5% rate of bleeding during the first two trimesters and 10% in the third trimester; miscarriage in up to 25%; premature delivery in 12%; and infections in 2%. The lowest risk of bleeding and miscarriage is in the second trimester, mainly between the 14th and 20th gestational weeks. Laser conization appears to be superior to other surgical methods in relation to the range of side effects [315], [800]. Laser vaporization and endocervical curettage are not indicated during pregnancy [800], [799], [801], [802].
The FIGO stage is determined on the basis of the clinical examination. Staging of invasive cervical carcinoma is carried out using ultrasound by an experienced ultrasonographer [96], with MRI and CT examinations in addition starting in the second trimester only after the indication has been very strictly established and following detailed consideration of the risk–benefit profile [800]. Lymph-node staging is carried out using MRI, with a good correlation between pathology and morphology [803] or using laparoscopic lymphadenectomy with low maternal and neonatal morbidity. Alternatively, lymphadenectomy can be performed as an open procedure as part of the cesarean operation [802], [804].
21.2 Epidemiology of and treatment planning for cervical carcinoma in pregnancy
Cervical carcinoma is the most frequent gynecological malignancy in pregnancy, with an incidence of 0.1–12 per 10,000 [802]. In Western industrialized nations, the incidence is 10–15 per 100,000 pregnancies. Around 70–80% of cervical carcinomas are diagnosed at FIGO stage I. The requirement for treatment depends on the stage of the disease, lymph-node status, histological subtype, gestational age, growth dynamics, acute symptoms (e.g., bleeding) and the patient’s desire to have children and preserve fertility [802]. Randomized clinical trials are not possible, and the evidence is therefore based on case series, case reports, and expert opinion. Interdisciplinary treatment in a level 1 perinatal center and gynecological cancer center should be required [802]. There is no evidence that pregnancy accelerates cervical cancer. The stage-adapted, tumor type–specific and tumor size–specific prognosis for pregnant patients is comparable with that in nonpregnant patients [805], [806].
21.2.1 Treatment options for cervical carcinoma in pregnancy relative to tumor stage and gestational age
The prognosis during the early stages (up to stage IB) seems to be similar to that in nonpregnant women [806], [807].
In the case of histologically confirmed CIN III or carcinoma in situ, one can await the end of the puerperium with tightly scheduled close-meshed colposcopic and clinical check-ups until surgical therapy can then be performed.
In cases of microinvasion (stage IA1 or IA2), a delay in therapy is acceptable without influencing the course of the disease, but regular clinical check-ups on the local findings are required [808], [809]. In FIGO stages IA1–IA2, conization can be recommended between the 14th and 20th weeks of gestation, with colposcopic check-ups conducted every 4–8 weeks thereafter, bearing maximum oncological safety in mind [808], [809]. The risk of bleeding is increased before gestational week 14 and after gestational week 20.
Laparoscopic lymphadenectomy for staging provides important information on the prognosis as early as stage IA2 in the presence of risk factors such as G3 and/or L1 and/or V1, but also at stage IB. Lymphadenectomy is possible and safe in gestational weeks 13–22, bearing maximum oncological safety in mind, and is associated with a good oncological and obstetric outcome [810], [811]. After gestational week 23, the size of the uterus severely limits the radicality of lymphadenectomy, and lymphadenectomy in the context of a postponed cesarean should therefore then be considered. A good option, particularly in the case of microinvasion and risk factors, as well as with tumors [Wright, J. D. et al. 2007].
If there is proven nodal involvement, termination of the pregnancy should at least be discussed in order to initiate radiochemotherapy promptly [812]. If the patient has a very strong wish to maintain the pregnancy, neoadjuvant chemotherapy may also be considered as an individual decision in order to gain time.
Fertility-preserving surgery is possible in early stages (up to stage IB1 [Wright, J. D. et al. 2007].
In the case of macroinvasive carcinoma, from the second trimester onwards pulmonary maturity is reached, and postponement of stage-appropriate surgery in the form of radical hysterectomy and lymphadenectomy, with neoadjuvant chemotherapy as well if appropriate, is an option in order to prolong the pregnancy [813]. In the meantime, neoadjuvant chemotherapy has become the standard if maintenance of the pregnancy is desired.
Neoadjuvant chemotherapy, with the option of delaying definitive surgical therapy until gestational week 32–34 in the context of the cesarean section, should be considered. No chemotherapy should be administered in the first trimester due to mutagenicity and teratogenicity and a high rate of miscarriage [814].
Chemotherapy is possible starting from the second trimester; the risks of growth retardation, fetal ototoxicity, and myelosuppression are known. Chemotherapy with cisplatin 50–100 mg/m2 q3w [804] or carboplatin AUC5 q3w / paclitaxel 80 mg/m2 body surface area weekly are possible [796], [815]. Chemotherapy should ideally be stopped 2–3 weeks before planned delivery in order to avoid delivery at the nadir. MRI and colposcopic check-ups, and tumor marker monitoring if appropriate, are recommended for monitoring therapy. No fetal malformations or perinatal morbidity were reported with cisplatin therapy in 21 pregnant women [816]. It is assumed that there is a placental filtration mechanism for platinum, as the platinum concentrations measured in cord blood are only 23–65%, and in amniotic fluid 11–42%, of those in maternal blood [816]. Although the data on the use of carboplatin during pregnancy are sparse, they appear to indicate lower toxicity [817].
Serious malformations have been reported in only 1.3% of infants born after chemotherapy administration from the second trimester onward, so that the risk is similar to that in the general population [814].
A meta-analysis on the use of neoadjuvant platinum-based chemotherapy in the second or third trimester, including 39 studies and 88 patients, showed generally encouraging results. The tumors were diagnosed at stages I–IIa in 87.5 % of cases; 86 patients received cisplatin and only two received carboplatin [306]. Cisplatin monotherapy was administered in 62.5% of the patients and 35.2% received combination therapy — with paclitaxel in 17 cases (35%), while one patient received a combination of carboplatin plus paclitaxel and one patient received carboplatin monotherapy. Complete remission was observed in 8.7% and partial remission in 46%, and stable disease in 42%. Adverse events were documented in only 25%, grade 3 toxicities were rarely reported, with thrombocytopenia and anemia in three patients and an allergic reaction to paclitaxel in one patient [306]. Eighty-eight neonates were reported from 84 pregnancies, with one set of twins and one set of triplets; 80.7% of them were born healthy. The preterm birth rate was 97.6% and the mean gestational age was 33.1 gestational weeks. One child was diagnosed with retroperitoneal embryonal rhabdomyosarcoma during the follow-up at 5 years of age, and another was diagnosed with acute myeloid leukemia at 29 months of age [306]. Recurrent cervical carcinoma was observed in 19.8% of the mothers during the course of the disease, and unfortunately 90% died. Radical hysterectomy with lymphadenectomy was performed during the cesarean procedure in 79% of the cases. Radical hysterectomy with pelvic lymphadenectomy was planned in only 2.3% as a secondary procedure after the cesarean during the later course (in some cases only after the puerperium). Radiochemotherapy alone was administered during the course in 3.9% [306]. In Germany, neoadjuvant platinum-based chemotherapy up to the cesarean, which is then followed by radical lymphadenectomy, is a frequently used variation. This is then followed by radiochemotherapy or radical hysterectomy after the puerperium, depending on the lymph-node stage and tumor stage.
The chemotherapy regimen currently recommended is platinum-containing chemotherapy (cisplatin 75 mg/m2), preferably with paclitaxel (175 mg/m2) at a 3-week interval or carboplatin AUC5 with paclitaxel (80 mg/m2), with an acceptable short-term toxicity profile [810].
Data on late toxicities are awaited. The vast majority of children show comparable motor and cognitive development [814], [818], [819]. The greatest risks of chemotherapy for the fetus during pregnancy are prematurity and growth retardation [820]. Platinum therapies increase the risk of myelotoxicity and ototoxicity in the fetus. With taxane-containing therapy, there is a higher rate neonatal intensive care treatment being needed [821], [822]. The risks to the mother also be need to be taken into consideration, of course, with myelotoxicity, ototoxicity, polyneuropathy, thrombosis and a risk of pulmonary embolism, among others. Anticoagulation treatment during ongoing therapy is therefore recommended.
If there is a good response with neoadjuvant chemotherapy, the pregnancy can be prolonged until 34+0 gestational weeks and even up to 37+0 gestational weeks if necessary, in order to avoid delivery of the fetus at a stage of extreme prematurity, with all the known consequences of prematurity.
21.2.2 FIGO stages IIB, III, and IV
A first diagnosis of FIGO stages II, III, and IV is rare during pregnancy. Treatment for the mother is in the foreground here, and platinum-based radiochemotherapy with cisplatin as the radiosensitizer should be performed. However, radiotherapy is not compatible with continuation of the pregnancy. The patient’s wishes and the week of gestation also need to be taken into account here. If the diagnosis is made in the second trimester, fetal pulmonary maturity can be awaited before treatment starts. Therapy consists of primary cesarean section and radiochemotherapy. If the initial diagnosis takes place at term, this procedure is the gold standard [800]. If the patient has a very strong desire to have the child, then initial neoadjuvant chemotherapy can be considered on an individual basis, with a markedly increased risk to the mother up to the time of the postponed primary caesarean and subsequent combined radiochemotherapy.
21.3 Mode of delivery
Vaginal delivery is not contraindicated in patients with preinvasive lesions. Spontaneous regressions during the puerperium after spontaneous birth have even been reported [800].
For microinvasive carcinomas (FIGO IA1), the data situation is unclear. Spontaneous delivery can only take place if a resection with healthy margins has been performed beforehand in the context of a conization; otherwise, a cesarean section should be performed. However, the majority of authors recommend cesarean section in this case as well.
For macroinvasive carcinomas (FIGO IB, IIA), cesarean section combined with stage-specific treatment in the form of radical hysterectomy and pelvic lymphadenectomy is the gold standard mode of delivery. A two-stage procedure is preferred. Hysterectomy is performed secondarily to reduce morbidity. In microinvasive cervical carcinoma with risk factors and stage IB [Pottharst, A. et al. 2009], [823].
21.4 Cervical carcinoma during pregnancy — a solvable dilemma
Diagnosis and treatment should be the same as in nonpregnant women. Therapeutic options should be discussed on an interdisciplinary basis, depending on the gestational age and the patient’s preferences. Fetal maturation can often be awaited. Abortion should be considered only in exceptional cases. Treatment for patients with cervical carcinoma in pregnancy is ideally performed in a gynecological cancer center and a level I perinatal center. Centralization is extremely useful, not least due to the rarity of cases. Suspicious or enlarged lymph nodes should be confirmed histologically in view of their prognostic significance and importance for further management. Laparoscopic, robotic, or laparotomic lymph-node staging during pregnancy up to gestational week 24 has shown valid results regarding the number of lymph nodes removed, with comparatively low morbidity. Depending on the tumor stage and gestational week, the following treatment options must be discussed with the patient, including the risks and benefits of individual approaches:
- Surgery, including tumor removal (conization, simple or radical cervicectomy, up to radical hysterectomy) and lymph-node staging (SNB if appropriate), depending on the stage of the disease, with the intention to preserve the pregnancy.
- Radical hysterectomy plus pelvic lymphadenectomy or primary radiochemotherapy: by analogy with the stage without preservation of pregnancy, with or without prior pregnancy termination.
- Delay in oncological therapy until viability (if possible > gestational week 32) and start of oncological therapy immediately after delivery by cesarean section or after the puerperium.
- Neoadjuvant chemotherapy to prolong the pregnancy until at most the end of prematurity, followed by cesarean section, including the necessary oncological therapy, particularly if there is a locally advanced stage or with residual tumor after conization that cannot be completely excised. In this case, laparoscopic lymph-node staging (with sentinel lymph-node excision if appropriate) should also be discussed before the start of neoadjuvant chemotherapy. Neoadjuvant platinum-based chemotherapy can be considered starting from gestational week 14 at the earliest.
- Cesarean (if possible) after gestational week 30 is the recommended mode of delivery.
- Either at the time of cesarean or as a secondary procedure (after the puerperium at the latest), definitive stage-adjusted oncologic therapy is recommended in the same way as in a nonpregnant patient, incorporating the treatment already administered during pregnancy.
- In summary, every patient with cervical carcinoma during pregnancy should be managed by an interdisciplinary team (gynecologic oncologist, obstetrician, neonatologist, anesthesiologist, radiation oncologist, and psycho-oncologist). A consensus treatment plan should be established, including patient’s intention, tumor stage, tumor biology, and gestational age at cancer diagnosis. The primary goals are oncological safety for the pregnant patient and the survival of the fetus without additional morbidity.
References
[796] Gaertner, J., Wuerstlein, R., Klein, U., Scheicht, D., Frechen, S., Wolf, J., et.al. Integrating Palliative Medicine into Comprehensive Breast Cancer Therapy - a Pilot Project, Breast Care (Basel), 2011. 6(3): p. 215-220., https://www.ncbi.nlm.nih.gov/pubmed/21779227
[797] Leitlinie Lymphödem der Sektion Pflege der DGP 2014, https://www.dgpalliativmedizin.de/images/stories/pdf/Leitlinie_Lymphödem_end.pdf
[798] Goncalves, C. V., Duarte, G., Costa, J. S., Marcolin, A. C., Bianchi, M. S., Dias, D., et.al. Diagnosis and treatment of cervical cancer during pregnancy, Sao Paulo Med J, 2009. 127: p. 359-65., https://www.ncbi.nlm.nih.gov/pubmed/20512291
[799] Ridner, S. H., Dietrich, M. S., Development and validation of the Lymphedema Symptom and Intensity Survey-Arm, Support Care Cancer, 2015. 23(10): p. 3103-12., https://www.ncbi.nlm.nih.gov/pubmed/25752884
[800] Pottharst, A., Steckkönig, A., Aulitzky, W., Subkutane Drainage zur Behandlung des malignen Lymphödems in der palliativen Situation nach Versagen der komplexen physikalischen Entstauungstherapie, Zeitschrift für Palliativmedizin, 2009. 10(01): p. 51-54., https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0028-1090170
[315] Wang, X. J., Fang, F., Li, Y. F., Sentinel-lymph-node procedures in early stage cervical cancer: a systematic review and meta-analysis, Med Oncol, 2015. 32(1): p. 385., https://www.ncbi.nlm.nih.gov/pubmed/25429838
[801] S2k_Fertilitätserhalt bei onkologischen Erkrankungen (AWMF-Registernummer 015/082; Version 1.0; September 2017), https://www.awmf.org/uploads/tx_szleitlinien/015-082l_S2k_Fertilitaetserhaltung-bei-onkologischen-Therapien_2017-12.pdf
[802] Plante, M., Renaud, M. C., Francois, H., Roy, M., Vaginal radical trachelectomy: an oncologically safe fertility-preserving surgery. An updated series of 72 cases and review of the literature, Gynecol Oncol, 2004. 94(3): p. 614-23., https://www.ncbi.nlm.nih.gov/pubmed/15350349
[96] Dappa, E., Elger, T., Hasenburg, A., Duber, C., Battista, M. J., Hotker, A. M., The value of advanced MRI techniques in the assessment of cervical cancer: a review, Insights Imaging, 2017. 8(5): p. 471-481., https://www.ncbi.nlm.nih.gov/pubmed/28828723
[803] Einstein, M. H., Park, K. J., Sonoda, Y., Carter, J., Chi, D. S., Barakat, R. R., et.al. Radical vaginal versus abdominal trachelectomy for stage IB1 cervical cancer: a comparison of surgical and pathologic outcomes, Gynecol Oncol, 2009. 112(1): p. 73-7., https://www.ncbi.nlm.nih.gov/pubmed/18973933
[804] Wright, J. D., Grigsby, P. W., Brooks, R., Powell, M. A., Gibb, R. K., Gao, F., et.al. Utility of parametrectomy for early stage cervical cancer treated with radical hysterectomy, Cancer, 2007. 110(6): p. 1281-6., https://www.ncbi.nlm.nih.gov/pubmed/17654664
[805] Selo-Ojeme, D. O., Ind, T., Shepherd, J. H., Isthmic stenosis following radical trachelectomy, J Obstet Gynaecol, 2002. 22(3): p. 327-8., https://www.ncbi.nlm.nih.gov/pubmed/12521522
[806] Covens, A., Rosen, B., Murphy, J., Laframboise, S., DePetrillo, A. D., Lickrish, G., et.al. How important is removal of the parametrium at surgery for carcinoma of the cervix?, Gynecol Oncol, 2002. 84(1): p. 145-9., https://www.ncbi.nlm.nih.gov/pubmed/11748991
[807] Jolley, J. A., Battista, L., Wing, D. A., Management of pregnancy after radical trachelectomy: case reports and systematic review of the literature, Am J Perinatol, 2007. 24: p. 531-9., https://www.ncbi.nlm.nih.gov/pubmed/17899494
[808] Cibula, D., Potter, R., Planchamp, F., Avall-Lundqvist, E., Fischerova, D., Haie-Meder, C., et.al. The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology Guidelines for the Management of Patients with Cervical Cancer, Virchows Arch, 2018. 472(6): p. 919-936., https://www.ncbi.nlm.nih.gov/pubmed/29725757
[809] Zhang, Q., Li, W., Kanis, M. J., Qi, G., Li, M., Yang, X., et.al. Oncologic and obstetrical outcomes with fertility-sparing treatment of cervical cancer: a systematic review and meta-analysis, Oncotarget, 2017. 8(28): p. 46580-46592., https://www.ncbi.nlm.nih.gov/pubmed/28418849
[810] Shim, S. H., Lim, M. C., Kim, H. J., Lee, M., Nam, E. J., Lee, J. Y., et.al. Can simple trachelectomy or conization show comparable survival rate compared with radical trachelectomy in IA1 cervical cancer patients with lymphovascular space invasion who wish to save fertility? A systematic review and guideline recommendation, PLoS One, 2018. 13(1): p. e0189847., https://www.ncbi.nlm.nih.gov/pubmed/29385139
[811] Ramirez, P. T., Pareja, R., Rendon, G. J., Millan, C., Frumovitz, M., Schmeler, K. M., Management of low-risk early-stage cervical cancer: should conization, simple trachelectomy, or simple hysterectomy replace radical surgery as the new standard of care?, Gynecol Oncol, 2014. 132(1): p. 254-9., https://www.ncbi.nlm.nih.gov/pubmed/24041877
[812] Speiser, Dorothee, Köhler, Christhardt, Schneider, Achim, Mangler, Mandy, Radikale vaginale Trachelektomie, Dtsch Arztebl International, 2013. 110(17): p. 289-295., http://www.aerzteblatt.de/int/article.asp?id=137444
[813] Bentivegna, E., Maulard, A., Pautier, P., Chargari, C., Gouy, S., Morice, P., Fertility results and pregnancy outcomes after conservative treatment of cervical cancer: a systematic review of the literature, Fertil Steril, 2016. 106(5): p. 1195-1211 e5., https://www.ncbi.nlm.nih.gov/pubmed/27430207
[814] Pareja, R., Rendon, G. J., Vasquez, M., Echeverri, L., Sanz-Lomana, C. M., Ramirez, P. T., Immediate radical trachelectomy versus neoadjuvant chemotherapy followed by conservative surgery for patients with stage IB1 cervical cancer with tumors 2cm or larger: A literature review and analysis of oncological and obstetrical outcomes, Gynecol Oncol, 2015. 137(3): p. 574-80., https://www.ncbi.nlm.nih.gov/pubmed/25827293
[815] Wallace, W. H., Thomson, A. B., Kelsey, T. W., The radiosensitivity of the human oocyte, Hum Reprod, 2003. 18(1): p. 117-21., https://www.ncbi.nlm.nih.gov/pubmed/12525451
[816] Kurt, M., Uncu, G., Cetintas, S. K., Kucuk, N., Guler, S., Ozkan, L., Successful spontaneous pregnancy in a patient with rectal carcinoma treated with pelvic radiotherapy and concurrent chemotherapy: the unique role of laparoscopic lateral ovary transposition, Eur J Gynaecol Oncol, 2007. 28(5): p. 408-10., https://www.ncbi.nlm.nih.gov/pubmed/17966224
[817] Lawrenz, B., Jauckus, J., Kupka, M., Strowitzki, T., von Wolff, M., Efficacy and safety of ovarian stimulation before chemotherapy in 205 cases, Fertil Steril, 2010. 94(7): p. 2871-3., https://www.ncbi.nlm.nih.gov/pubmed/20678763
[306] Frumovitz, M., Plante, M., Lee, P. S., Sandadi, S., Lilja, J. F., Escobar, P. F., et.al. Near-infrared fluorescence for detection of sentinel lymph nodes in women with cervical and uterine cancers (FILM): a randomised, phase 3, multicentre, non-inferiority trial, Lancet Oncol, 2018. 19(10): p. 1394-1403., https://www.ncbi.nlm.nih.gov/pubmed/30143441
[818] Irtan, S., Orbach, D., Helfre, S., Sarnacki, S., Ovarian transposition in prepubescent and adolescent girls with cancer, Lancet Oncol, 2013. 14(13): p. e601-8., https://www.ncbi.nlm.nih.gov/pubmed/24275133
[819] Mossa, B., Schimberni, M., Di Benedetto, L., Mossa, S., Ovarian transposition in young women and fertility sparing, Eur Rev Med Pharmacol Sci, 2015. 19(18): p. 3418-25., https://www.ncbi.nlm.nih.gov/pubmed/26439037
[820] Kim, J., Turan, V., Oktay, K., Long-Term Safety of Letrozole and Gonadotropin Stimulation for Fertility Preservation in Women With Breast Cancer, J Clin Endocrinol Metab, 2016. 101(4): p. 1364-71., https://www.ncbi.nlm.nih.gov/pubmed/26751194
[821] Salih, S. M., Albayrak, S., Seo, S., Stewart, S. L., Bradley, K., Kushner, D. M., Diminished Utilization of in Vitro Fertilization Following Ovarian Transposition in Cervical Cancer Patients, J Reprod Med, 2015. 60(7-8): p. 345-53., https://www.ncbi.nlm.nih.gov/pubmed/26380495
[822] Teh, W. T., Stern, C., Chander, S., Hickey, M., The impact of uterine radiation on subsequent fertility and pregnancy outcomes, Biomed Res Int, 2014. 2014: p. 482968., https://www.ncbi.nlm.nih.gov/pubmed/25165706
[823] Tummers, P., Goker, M., Dahm-Kahler, P., Brannstrom, M., Tullius, S. G., Rogiers, X., et.al. Meeting Report: First State-of-the-Art Meeting on Uterus Transplantation, Transplantation, 2019. 103(3): p. 455-458., https://www.ncbi.nlm.nih.gov/pubmed/30747845