Approximately 46% of cervical cancer patients are of reproductive age. It is important to discuss fertility-sparing surgery in candidates with newly diagnosed early stage (stage IB1 or less) cervical cancer [1]. Per the National Comprehensive Cancer Network guidelines, radical trachelectomy (RT) is a safe oncologic treatment in patients with early stage cervical cancer [12]. Many studies have concluded that pregnancy after RT is feasible and can be successful [345]. However, this surgery comes with potential postoperative complications that may make pregnancies high risk [6]. Common complications include cervical stenosis and cervical insufficiency, which can lead to difficulty conceiving, infertility, preterm delivery, first- or second-trimester miscarriage, and preterm premature rupture of membranes [346789].

A systematic review analyzing fertility and pregnancy outcomes among women who underwent RT performed by all surgical approaches (i.e., vaginal RT, abdominal RT, minimally invasive RT) concluded that the rates of pregnancy (patients with at least 1 pregnancy/total number of patients attempting pregnancy), live birth, and prematurity (<36 weeks) were 55%, 71%, and 49%, respectively [8]. Carter et al. [10] reported that postoperative complications can affect patients physically and emotionally and highlighted the importance of informing patients of what to expect from RT and of future implications for their health. Carter et al. [11] also demonstrated no significant differences in mood, quality of life, distress, or sexual function between patients with early stage cervical cancer who underwent RT and those who underwent radical hysterectomy. This information can help reproductive endocrinologists give patients reasonable expectations about fertility and pregnancy outcomes and can assist gynecologic oncologists when counseling patients on the recovery process.

After RT, possible outcomes that may increase the rate of infertility include cervical stenosis, lack of cervical mucus to facilitate sperm migration, subclinical endometritis, and vascular compromise [6812]. Prior studies have investigated sexual function [13], quality of life [111], emotional and physical well-being [11], and pregnancy outcomes [38] after RT, but there is a paucity of data describing the role and extent of reproductive counseling in this patient population [14]. The purpose of this study was to determine how patients perceive preoperative reproductive counseling (i.e., effects on future fertility, pregnancy risks/complications) and to evaluate postoperative complications and pregnancy outcomes in patients who underwent RT for early stage cervical cancer.

This survey-based cross-sectional study was approved by the Institutional Review Board at The University of Texas MD Anderson Cancer Center (PA17-0641). All patients who underwent RT at MD Anderson Cancer Center from January 1, 2004, through July 31, 2017, and had been cancer free for more than 1 year after RT were eligible. These patients were initially contacted via a mailed letter that introduced and described the research study and were then contacted by a telephone call or by an email message sent through MD Anderson Cancer Center's secure web-based system to determine if they were willing to participate. Once a patient was consented, demographic information, pregnancy outcomes, surgical details, and postsurgical complications were obtained by retrospective chart review. A 16-item online questionnaire was developed by our multidisciplinary research team containing a combination of quantitative and qualitative items (Supplementary Data 1). Survey questions were presented as multiple choice, Likert scale, or open-ended questions. All collected patient information was confidential, and no identifiers were used in the analysis. Surveys were collected and managed using Research Electronic Data Capture (REDCap) tools hosted at MD Anderson Cancer Center [15]. Patients who had agreed to participate but not started the survey were sent an email reminder via REDCap up to 3 times. We followed the Strengthening the Reporting of Observational Studies in Epidemiology [16] guidelines in reporting the results of our study. Descriptive statistics were used to report all variables of interest; categorical variables were analyzed using the sign test and Fisher's exact test. A p-value less than 0.05 was considered statistically significant.

This study explored how patients with early stage cervical cancer who underwent RT perceived preoperative reproductive counseling; the study also evaluated the patients' postoperative complications and pregnancy outcomes. Our survey response rate of 67% exceeds the goal of 60% that has been established by researchers as an adequate recruitment goal in survey studies [17]. Our study demonstrated that a significant proportion of patients who underwent RT at our institution reported not receiving reproductive or pregnancy risks and complications counseling in the preoperative period. Patients in our study reported that they would have preferred more detailed reproductive counseling with a reproductive endocrinologist prior to surgery. Given the significant rate of infertility or subfertility and higher obstetrical risks associated with RT, we recommend a preoperative consultation with a reproductive endocrinologist for all patients who are considering RT for treatment of early stage cervical cancer.

With our results, our institutional policy has changed to offer preoperative consultation with a reproductive endocrinologist to all eligible RT patients. Having provider-initiated conversations regarding future fertility are important as patients with a recent diagnosis of cervical cancer may be focusing more on the cancer and its treatment than on future fertility. Early preoperative counseling by a reproductive endocrinologist can complement oncologic care by helping patients understand how RT may affect future fertility, discuss reproductive outcomes and complications, and help standardize reproductive counseling [61218]. If counseling is done preoperatively, the reproductive endocrinologist can evaluate a patient's reproductive potential by evaluating a patient ovarian reserve, ruling out ovulatory dysfunction or tubal factor, and discuss any pertinent reproductive history (i.e., recurrent miscarriages, uterine cavity abnormalities) to ensure the patient is an appropriate candidate for RT from a future fertility standpoint. In addition, the reproductive endocrinologist can discuss different fertility treatments and future management strategies if necessary [618]. Having reproductive and oncologic counseling in 2 separate sessions may allow patients to give the attention needed for the important information delivered by the physician.

Before RT, reproductive counseling can also help set realistic expectations regarding pregnancy after RT and return to postsurgical changes (i.e., change in the level of sexual desire, dyspareunia, menstrual changes, emotional stress) [110]. If patients have realistic expectations, they may be more proactive in trying to conceive by seeing a reproductive endocrinologist prior to surgery instead of waiting for 1 to 2 years before pursuing a fertility treatment (e.g., IVF, intrauterine insemination, ovulation induction) if needed. Other studies have demonstrated that patients who have undergone RT often need some sort of fertility treatment in order to conceive and have a successful live birth [23919]. This is consistent with our data and supports the need for a consultation with a reproductive endocrinologist preoperatively before RT allowing patients to seek a fertility treatment sooner if needed and decrease the time to conception.

Similar to other studies, our study demonstrated that live births were possible after RT [28]. Our pregnancy rate of 54% (13/24 patients) is similar to the pregnancy rate in a systematic review (55%, 515/938) that included all surgical approaches for RT [8]. Compared to the findings of another systematic review, on pregnancy outcomes after abdominal and vaginal RT, our pregnancy rate (54% vs. 66%), live birth rate (70% vs. 63%), and rate of spontaneous miscarriage were all similar (25% vs. 24%) [7].

Our finding that cervical stenosis effected 33% of patients is higher than the average rate of 10.5% calculated in a published meta-analysis reviewing this complication [20]. There is, however, a wide range of cervical stenosis rates reported in the literature. For example, in that study 20% of the publications reviewed reported a stenosis rate >20% with one large series describing the complication in 73% of patients while 4 studies described 0% of patients experiencing cervical stenosis [20]. The rate of cervical stenosis reported in this study may be higher than the average in that meta-analysis as we relied upon self-reporting by patients and not physician assessed cervical stenosis.

Patients with infertility for other reasons may have inaccurately attributed their difficulties getting pregnant to cervical stenosis as opposed to other etiologies. Our study has some limitations. This survey was not validated; however, the survey questions were developed by a team consisting of gynecologic oncology and reproductive endocrinology with the intent of soliciting the data to best capture patient responses. With a survey format and use of medical terminology, patients may not have interpreted the questions as we intended. In future studies, defining reproductive and pregnancy risk/complication counseling while minimizing medical terminology in survey questions may limit variations in patient interpretation. Despite having an adequate response rate, the overall low number of patients needs to be considered when interpreting our conclusions. Documentation of reproductive counseling by providers was inconsistent and not able to be used as a comparison with our survey responses. Recall bias or variation in patient perception may have influenced our data. Future studies should correlate patient perceptions to documentation of reproductive counseling by providers. Additionally, since the study included patients treated over an 11-year period, fertility treatment options markedly changed from 2004 to 2017 which may have influenced how reproductive counseling was performed and patients desire for pregnancy. Given our study was conducted at one institution, our conclusions may not be generalizable to all centers who offer RT; reproductive counseling assessment needs to be studied at other institutions. Further research is needed to accurately assess patient perceptions of preoperative reproductive counseling and how they may be impacted by including consultation with a reproductive endocrinologist in the preoperative counseling process.

To our knowledge, this is one of the first studies to provide data on the frequency and patient perceptions of preoperative reproductive counseling in patients undergoing RT for early stage cervical cancer. In addition, we report on obstetrical outcomes after abdominal or pure laparoscopic RT and one of the few studies to provide obstetrical outcomes after robotic-assisted laparoscopic RT. Our data demonstrated that many patients who undergo RT do not receive preoperative reproductive counseling. Having a preoperative consultation with a reproductive endocrinologist can increase patient education by helping patients understand how RT may affect future fertility, ensure patients are adequately informed before making surgical treatment decisions, and facilitate a proactive approach towards achieving a successful pregnancy.