Fertility preservation for young survivors

By Aimee Chism Holland, DNP, WHNP-BC, FNP-BC, RD; Deborah Kirk ervical cancer was once the Walker, DNP, FNP-BC, NP-C, AOCN; Sigrid Ladores, PhD, PNP; and leading cause of gyneco - Karen Meneses, PhD, RN, FAAN Clogic cancer in the United States. Following introduction of the About 68% of invasive cervical cancer cases diagnosed in the use of the Pap smear in the 1940s, the incidence of cervical cancer has United States involve women of childbearing age. Current declined dramatically. 1 Because use treatment options for young patients with cervical cancer may of the Pap smear is so effective and cause hormonal and/or structural modifications to the so widespread, the diagnosis of cer - reproductive system that could compromise pregnancy potential. vical cancer, when it is found, is usu - ally made when a woman is younger Although clinical guidelines are available to help preserve (and still fertile) and when the dis - fertility in these patients, gaps in practice remain, suggesting that ease is at an earlier stage (and there - the fertility-sparing needs of cervical cancer survivors are not fore more easily treated). In 2014, the American Cancer routinely met. The authors provide nurse practitioners with Society projected that 12,360 new current evidence about fertility-sparing treatments and with cases of cervical cancer would be 2 counseling considerations for young cervical cancer survivors. diagnosed in the U.S. Approxi - mately 68% of cervical cancer cases are diagnosed in women of child - KEY WORDS : cervical cancer survivor, fertility-sparing treatment, 3,4 pregnancy, infertility, conization, trachelectomy bearing age. For young women, a diagnosis of cervical cancer once meant a hysterectomy and loss of the ability to bear a child. Today, fertility-sparing treatment (FST) op - tions exist for women with early- stage cervical cancer, as well as more advanced fertility preserva - tion and assisted reproductive tech - nology (ART) approaches for those who are not candidates for FST. 5 Young cervical cancer survivors may not know about FST options, and thus fear that treatment for cancer may compromise their fu - ture ability to conceive. 6 Survivors also tend to be anxious about pregnancy outcomes after com - pleting cancer treatment. 7,8 Evi - dence suggests that they will want to discuss future fertility options

40 May 2015 Women’s Healthcare www.NP WOMENS HEALTHCARE .com Table 1. FIGO cervical cancer clinical staging 5 with their healthcare provider workup (HCP). 9 The American Society of • History and physical examination Clinical Oncology (ASCO) and the • Chest radiograph American Society of Reproductive • Complete blood count Medicine have published guide - • CT or PET-CT scan lines recommending that, prior to • Cervical biopsy treatment, HCPs educate patients • MRI as indicated diagnosed with cervical cancer • Cone biopsy as indicated about the treatment’s potential effects on their fertility, along • HIV testing as indicated with fertility-preservation • Smoking cessation and counseling as indicated options. 10,11 However, many HCPs • Cystoscopy or proctoscopy for patients in whom are uninformed themselves and bladder/bowel involvement is suspected do not routinely offer fertility- CT, computed tomography; FIGO, International Federation of Gynecology preservation counseling prior to and Obstetrics; MRI, magnetic resonance imaging; PET, positron emission cancer treatment. 12,13 The pur - tomography. pose of this article is to provide HCPs with current evidence about FST for cervical cancer and with oung cervical cone biopsy or radical trachelec - counseling recommendations for Y tomy for treatment for up to cervi - young cervical cancer survivors. cancer survivors may cal cancer stage IB1 in women who want to preserve their fertility. 5 This Diagnosis and staging of not know about recommendation has not always cervical cancer existed; trends in surgical manage - A Pap smear is used to screen for fertility-sparing ment of low-risk early-stage lesions cervical cancer but not to make the have changed over the past 20 diagnosis. A histology report from a treatment options, years. Hysterectomy was the only cervical biopsy confirms the diag - cure for cervical cancer stage IB1 nosis and type of cervical cancer. and thus fear that until Dargent developed the fertil - After diagnosis, a workup is done to ity-sparing radical vaginal trach - determine disease stage ( Table 1 ). 5 treatment for cancer electomy (RVT) technique in A clinical staging system is used may compromise 1994. 17 Prior to RVT, women with for cervical cancer (rather than the stage IA1 or IA2 lesions were the surgical criteria used for most their future ability only cervical cancer survivors able other gynecologic cancers). Two to preserve their fertility. 15 different staging systems are avail - to conceive. able. The International Federation Cone biopsy of Gynecology and Obstetrics This term refers to a wedge- (FIGO) staging system is based on American Joint Committee on Can - shaped excision of cervical tissue a physical examination, diagnostic cer created the TNM system, which for both diagnostic evaluation procedures, and imaging studies. is based on extent of the tumor and removal of abnormal tissue. Stages IA1, IA2, and IB1 are con - (T), node involvement (N), and dis - Two methods of obtaining a cone sidered early stages of cervical tant metastases presentation (M). biopsy with fertility sparing in cancer. 5,14 In stages IA1 and IA2, Each stage in this system has sub - mind are cold knife conization cancer is confined to the stages that further describe tissue (CKC) and the loop electrosurgi - and diagnosed only microscopi - involvement ( Table 2 ). 5,15,16 cal excision procedure (LEEP). cally. Stage IB1 describes cancer Cone biopsy is used to treat small confined to the cervix with a clini - Fertility-sparing cervical lesions when there is no risk of cally visible tumor ≤4 cm, stromal cancer treatment dissecting across a gross neo - invasion <10 mm, and no lymph The National Comprehensive Can - plasm. 5 Given that adequate mar - vascular space invasion. 5 The cer Network (NCCN) recommends gins and correct orientation are www.NP WOMENS HEALTHCARE .com May 2015 Women’s Healthcare 41 Table 2. Cervical cancer staging systems 5,15,16

AJCC TNM FIGO tients who tried to conceive, 6 stage stage Description achieved a spontaneous preg - T1 I Carcinoma confined to the cervix nancy and 4 received conception assistance via in vitro fertilization T1a IA Microscopy-visualized invasive carcinoma and embryo transfer (1 of whom with deepest invasion ≤5 mm and largest achieved a pregnancy). In total, extension ≤7 mm 70% of the young survivors T1a1 IA1 Measured stromal invasion ≤3 mm in achieved a pregnancy after cone depth and largest extension ≤7 mm biopsy treatment. T1a2 IA2 Measured stromal invasion >3 mm and Trachelectomy ≤5 mm, with largest extension ≤7 mm This fertility-sparing surgical proce - T1b IB Clinically visualized lesion confined to the dure is performed to eradicate cer - cervix uteri or preclinical cancers greater vical cancer. In an RVT, the uterine than stage T1a/IA2 corpus, ovaries, and Fallopian T1b1 IB1 Clinically visualized lesion ≤4 cm in tubes are preserved, but the cervix, greatest dimension upper portion of the , and the supporting ligaments are re - T1b2 IB2 Clinically visualized lesion >4 cm in moved. A cerclage is placed at the greatest dimension location of the isthmus to close the AJCC, American Joint Committee on Cancer; FIGO, International Federation of opening of the . 7 RVT is an Gynecology and Obstetrics. option for patients with stage IA2 or IB1 lesions <2 cm in diameter. A radical abdominal trachelectomy is obtained, CKC and LEEP are ap - used for stage IB1 lesions >2 cm propriate measures for cervical Most women who and ≤4 cm, and provides a larger cancer stage IA1 without lym - undergo radical resection of the parametria. 5 phovascular space invasion. 5 Most women who undergo RVT Negligible risks exist for cervical vaginal are able to conceive sponta - cancer stage IA1 recurrence fol - neously, but a small number will lowing this treatment. 5 trachelectomy are require conception assistance. 21 Potential risks regarding future The 5-year cumulative pregnancy fertility following a cone biopsy able to conceive rate for women trying to conceive include cervical stenosis and post-RVT is 52.8%; the cervical preterm delivery. 18,19 Cervical spontaneously . cancer recurrence rate after the stenosis occurs in 2%-3% of pa - procedure continues to be low. 7 tients after CKC and in 3%-4% biopsy sample was thicker than Potential risks of either trachelec - post-LEEP. 19 Because of scar tis - 1.2 cm and larger than 6 cm 2. tomy procedure with regard to fu - sue formation that can occur af - However, Bevis and Biggio 18 re - ture fertility include miscarriage, ter a cone biopsy, fertility may be ported that evidence for the ef - preterm delivery, , and compromised until the tissue is fects of conization procedures on isthmic stenosis. 7,21 removed from the cervix. Long fertility was conflicting because Koh et al 5 reported that, world - and Leeman 19 reported that a of the different types of proce - wide, more than 300 pregnancies history of a cone biopsy in - dures performed and the varying have been confirmed following a creased the odds of a preterm quality of control groups. trachelectomy for cervical cancer. delivery by 2.19 (95% confidence Fanfani et al 20 performed a Risk for second trimester miscar - interval, 1.93-2.49); risk corre - multicenter retrospective analysis riage following a trachelectomy is lated with the depth of the trans - of reproductive outcomes in 23 10%. However, 72% of women formation zone removed. In this early-stage cervical cancer sur - have carried a pregnancy to term. study, a greater risk existed for vivors who had undergone coni- Park et al 22 conducted a retrospec - preterm delivery when a cone zation treatment. Among 10 pa - tive chart review of 55 young

42 May 2015 Women’s Healthcare www.NP WOMENS HEALTHCARE .com Table 3. Resources early-stage cervical cancer sur - • American Cancer Society: Fertility and Women with Cancer: vivors who underwent laparo - www.cancer.org/acs/groups/cid/documents/webcontent/ scopic abdominal trachelectomy. acspc-041244-pdf.pdf Ten of 18 patients attempting a • American Society of Clinical Oncology: www.asco.org/ pregnancy conceived; 6 of the 10 • Cancer Research UK: Fertility and Cervical Cancer: experienced preterm delivery. www.cancerresearchuk.org/about-cancer/type/cervical-cancer/ Overall, 55.6% of the survivors living/fertility-and-cervical-cancer achieved a pregnancy, with 60% • Having-babies-after-cervical-cancer.com delivering preterm. www.having-babies-after-cervical-cancer.com/fertility.html • Livestrong Foundation. Female Fertility Preservation Fertility preservation www.livestrong.org/we-can-help/just-diagnosed/female-fertility- procedures preservation/ Most women with cervical cancer • National Cervical Cancer Coalition: www.nccc-online.org/ at stage IB2 or greater are not can - • Resolve: The National Infertility Association: www.resolve.org/ didates for FST. • Save My Fertility: http://www.savemyfertility.org/ is most often used for patients with higher stage IB disease, often • The Oncofertility Consortium: http://oncofertility.northwestern.edu/ called bulky disease. Radiation therapy is also used following a primary radical hysterectomy or in tions concerning fertility preser - conjunction with chemotherapy in Inform patients of vation were issued by ASCO: (1) advanced disease. Radiation that Assume that patients with cancer includes the ovaries can damage their individual want to discuss fertility preserva - oocyte quality and sex hormone tion; address the possibility of in - production. Chemotherapy is not risk for fertility before cancer treatment used in patients with milder forms infertility , based starts and work with an interdisci - of cervical cancer who are consid - plinary team to formulate a plan ering FST options. on disease stage and and make appropriate referrals; Women planning to undergo ra - (2) Present oocyte and embryo diation still have fertility preserva - treatment, as high, cryopreservation as established tion options, including the ART pro - fertility preservation methods; (3) cedures of oocyte or embryo medium, low, or Discuss the option of ooph- cryopreservation prior to cancer oropexy when pelvic radiation treatment. 23 Cryopreservation of nonexistent. will be performed; (4) Inform pa - unfertilized oocytes, as opposed to tients of their individual risk for embryos, may be considered for pa - opment. However, guidelines from infertility, based on disease stage tients who do not have a male part - both the American Congress of and treatment, as high, medium, ner, do not wish to use donor Obstetricians and Gynecologists low, or nonexistent; and (5) In - sperm, or have religious or ethical and ASCO indicate insufficient evi - form patients about the use of reasons for avoiding embryo freez - dence regarding the effectiveness conservative gynecologic surgery ing. Because oocytes are highly of gonadotropin-releasing hor - and radiation options. 11 sensitive to radiation injury, a pro - mone analogs to suppress and Several organizations and advo - cedure called ooph oropexy (ovar - protect ovarian function during cacy groups are available for young ian transposition) may be used. cytotoxic treatment. 24 cervical cancer survivors with fertil - With ooph oropexy, ovaries are su - ity concerns both before and after tured to the posterior uterus to pro - Counseling before treatment treatment ( Table 3 ). ASCO created a tect them during pelvic radiation. These counseling recommenda - video A that can educate young pa - Before or after cancer treat - ment, survivors may benefit from ovarian stimulation medications VIEW : Fertility preservation for young women with cancer A that help promote follicular devel - www.NP WOMENS HEALTHCARE .com May 2015 Women’s Healthcare 43 Table 4. Physical and psychological problems 25-27 involving sexual function in helping resolve the problem. Physical problems Psychosocial problems Nonpharmacologic and pharma - cologic treatments, along with al - Adhesions Anxiety ternate positioning during inter - Changes in energy level Arousal difficulties course, can be offered. HCPs can Damage to nerves Changes in relationships recommend over-the-counter Decreased intimacy Depression vaginal moisturizers and lubri - Decreased libido Fear (of change) cants to assist with vaginal dry - Decreased vaginal elasticity Fear (or recurrence) ness, , and sexual Difficulty with conception Lack of desire stimulation. In addition, prescrip - Difficulty with lubrication Reproductive concerns tion-strength topical lidocaine, Dyspareunia Sexual worry estradiol vaginal cream, or os - Fatigue pemifene may help. Undergoing ART can be arduous Fibrosis Drug classes that can affect Inflammation libido for women who endure painful and costly treatments. As of 2008, Miscarriage Antidepressants only 15 states have mandates that Preterm delivery Anxiolytics require health insurance carriers to Radiation Opioids provide full or partial coverage of Risk of infertility costs related to infertility treat - Scarring ments. 28 Most couples or individ - Surgery ual women pay for infertility treat - Vaginal stenosis ments out of pocket. Each ART cycle requires a woman to invest her body, mind, time, and money tients about fertility preservation mention sexual problems on their to realize her dream of mother - options and support networks. own, so HCPs need to inquire hood, and she may be placing her - about them and make referrals to self at risk for developing anxiety Counseling after treatment a counselor who specializes in and depression. 29-31 A woman who has undergone FST sex therapy, a gynecologist, or a Even if a woman succeeds in for cervical cancer faces many physical therapist who specializes achieving pregnancy through ART, challenges. She may experience in pelvic pain and sexual dysfunc - the process is often fraught with distress, depression, anxiety, tion.* Many of the physical and anxiety. 32,33 Young female cancer and/or fear, and, depending on psychological complaints involv - survivors have reported that they her own innate coping ability and ing sexual function resolve with- have a hopeful yet worried out - her support system, may require in the first year after treatment look on fertility and mother - psychological assessment and re - but may last up to 2 years or long - hood. 34 This worry is especially ferral. HCPs can evaluate patients er. 25,26 true for cervical cancer survivors for these psychological reactions With regard to dyspareunia in who have had trachelectomy sur - with tools such as the Functional particular, asking patients whether gery, as reported by Lloyd et al, 7 Assessment of Cancer Therapy- they experience it is the first step wherein several participants de - Cervical Cancer Subscale B and scribed how they were fearful dur - the NCCN Distress Thermome - *Editor’s Note: In the current issue of ing pregnancy and attempted to ter for Patients C, and make refer - Women’s Healthcare: A Clinical Journal for be “model” pregnant women who rals as needed. NPs , Tammy M. DeBevoise, PT, DPT; An - followed every recommendation Cervical cancer and its treat - gela F. Dobinsky, PT, DPT; Caitlin B. Mc - to reduce risks associated with ment can adversely affect sexual Curdy-Robinson, PT, DPT; Christina M. preterm labor and miscarriage. McGee, PT, DPT, ATC, LAT; Cody E. Mc - health, causing problems such as Neely, PT, DPT; Sara K. Sauder, PT, DPT; Consultations with specialists in decreased libido, fatigue, vaginal and Kimberlee D. Sullivan, PT, DPT, WCS, reproductive endocrinology stenosis, and dyspareunia ( Table BCB-PMD present a feature-length arti - and/or high-risk obstetrics may be 4). 25-27 Many women hesitate to cle on pelvic floor physical therapy. helpful. Pregnancy loss after infer -

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