Gynecological malignancies are most often diagnosed in postmenopausal women, but there is a subset of women who are of child bearing age. Fertility preservation becomes an important issue in these women.

There are several important facts that need to be considered before offering these women with fertility sparing surgical options. Firstly, there must be a strong desire on the part of the patient or in the case of a child, of her parents to retain fertility. Secondly, fertility should be preserved without compromising the oncological safety; thereby ‘optimal cancer therapy should always supersede fertility preservation as a primary objective’. Thirdly, patients should be told that data on fertility sparing procedures are limited and that many of these options are of an experimental non-standard nature. When one considers these important facts, the number of young patients who may be candidates for the fertility preserving surgeries get limited.

Ovarian Cancer
15% of the ovarian cancers occur in young women, some of whom may want to preserve their reproductive potential. The sub-categories of patients who are appropriate for such management include those with:

a) Tumors of low malignant potential
b) Stage-Ia invasive epithelial ovarian cancer with nonclear cell histology, (grade I and II)
c) Malignant germ cell tumors
d) Malignant sex cord stromal tumor.

Fertility sparing surgical options for them include ovarian cystectomy, unilateral salpingo-ophorectomy, unilateral salpingo-ophorectomy plus hysterectomy (with preservation of contralateral ovary) and bilateral salpingo-ophorectomy (with preservation of the uterus). In the latter two procedures assisted reproductive technology (ART) is necessary to achieve pregnancy. A comprehensive surgical staging should always be performed in conjunction with these procedures.

Tumors of low malignant potential (borderline ovarian tumors) constitute 10-15% of epithelial ovarian tumors; they are often diagnosed incidentally after ovarian cystectomy or unilateral oophorectomy in young women.

The risk of ipsilateral recurrence is 6% and that of contralateral/bilateral recurrence each is 3% after fertility sparing surgery. The recurrence rate is similar in the radical and fertility sparing surgery group. Those patients who have recurrence limited to the residual ovary can be salvaged with a second round of fertility sparing surgery. According to literature review conducted over a period of 12 years (1997-2009), out of the 51 patients who had undergone conservative surgery 45 conceived (88%).

Invasive epithelial ovarian cancers are usually diagnosed in postmenopausal women in an advanced stage. Approximately 25% of tumors are in Stage I, and this early stage disease is associated with 5 year survival rate of 90%. ACOG (2007) and European Society of Medical Oncology (ESMO, 2008) recommend fertility sparing surgery for Stage Ia non-clear cell histology (Grade I and II tumors). Even with stage Ia disease, postoperative platinum based chemotherapy is recommended for those patients with high risk factors. However there is a risk of relapse. Retrospective review conducted over a period of 20 years has shown the recurrence rate to be 15% in conservative surgery group and 19% in standard surgery group. Also the 5 year survival data showed no significant difference in recurrence free survival (84% vs 78%) and overall survival (84% vs 82%). When fertility data were analyzed 96% patients gave information of return of menstruation in the same cycle, 5% patients developed secondary amenorrhea consequent to chemotherapy. 195 0f the 211 patients who attempted to conceive had a pregnancy rate of 28.5%.

Malignant germ cell tumors are usually seen in young women. They are mostly unilateral and 60% are in stage I. Dysgerminomas are the only exception and 15% of them are bilateral. Due to young age of presentation, fertility preservation is extremely important in these women. These patients should be offered unilateral salpingoophorectomy or unilateral salpingo-ophorectomy with contralateral ovarian cystectomy (for bilateral tumors). Literature review has shown that the survival rate following conservative surgery is 90-100% versus 89-100% for radical surgery. Zanetta and colleagues have reported the largest experience of fertility sparing procedures in young women with malignant germ cell tumors. According to them 88% of the patients who attempted to conceive became pregnant and 69% achieved full term birth irrespective of their requirement for chemotherapy. Some patients who require chemotherapy (except stage I dysgerminoma and stage Ia grade I immature tertatoma) may have premature ovarian failure. Inspite of this fertility sparing options should be offered taking into account the beneficial effect available to the others and cure rates approaching 100%. It has also been reported that the pregnancies are usually successful and there is no reported increase in the incidence of gross congenital malformations post chemotherapy.

Sex cord stromal tumors are uncommon and account for 5% of ovarian neoplasms and 7% of malignant ovarian tumours. Clinically they often present with no distinguishing features, but some are functional and may cause virilization or symptoms from excess estrogen secretion, such as endometrial hyperplasia and postmenopausal bleeding (PMB). The most common form in this group is the granulosa cell tumor, this is usually seen in postmenopausal women, however, a variety, juvenile granulose cell tumor is mostly diagnosed before 20 years of age. The tumours are usually unilateral. In younger patients with apparently localized disease, fertility sparing surgery should be discussed, as there is no indication that treatment or prognosis is affected by a full staging procedure.

Cancer Cervix
Early-stage cervical cancer often presents in women of fertile age and the traditional treatment has been radical hysterectomy with pelvic lymphadenectomy, or chemoradiotherapy. As medical science has advanced there has been a gradual abandonment of radical surgical procedures in favour of more conservative techniques in an effort to decrease morbidity and preserve fertility without compromising overall survival. Various fertility sparing surgeries appropriate for cancer cervix include conization, radical trachelectomy (vaginal/abdominal/ laproscopic) and ovarian transposition.

Cervical conization (cone biopsy) refers to the excision of a cone shaped portion of the cervix surrounding the endocervical canal and including the entire transformation zone. This can be performed using a scalpel, laser, or electrosurgery (LEEP/LLETZ). Conization is an appropriate management for patients with FIGO stage IA1 with no lymphovascular space invasion (LVSI). Residual microinvasive cancers have been reported in 5% of patients and the risk factors identified include positive margins and positive endocervical curettings. But In the largest study done till date involving 200 patients, no patient developed any recurrence over a follow up period of (72-420) months.

Radical trachelectomy can be performed vaginally, abdominally or laproscopically. Radical vaginal trachelectomy (RVT) was first described by Daniel Dargent in 1994 and involves removal of most of the cervix, its contiguous parametrium, and vaginal cuff, in addition to a laparoscopic pelvic lymphadenectomy. RVT is considered an appropriate management for patients with FIGO stage IAI with LVSI, stage IA2 and stage IB1 as early stage cancer tends to spread laterally from the cervix into the parametrium and inferiorly to the upper vagina and not superiorly to the uterine corpus.

Patients with cervical cancer who undergo RVT are followed every 3 months for 2 years, then every 6 months for 3 years, and then yearly. Each visit entails a Pap smear in addition to the history and clinical examination. However, Pap smear has not found to be useful in detection of recurrence and has been given up in many
centres. Some centres do a high risk HPV testing once a year. Radiological studies are individualized.

RVT has to be aborted in 11-12 % cases due to lymph node metastasis, more extensive disease than expected or inability to achieve a negative cervical margin; these patients then require additional treatment. Recurrence rate following RVT is similar to that of radical hysterectomy (3%). The risk factors include lesion size greater than 2 cm, LVSI and unfavourable histology (small cell neuroendocrine tumor).

Pregnancy rates following RVT range between 41% and 79%, and term delivery (≥37 weeks) is reached in 38% of the pregnancies¹¹. These patients do not show any increase in first trimester complications, however the second trimester loss and preterm births are increased in comparison to the general population. As these patients have no/minimal lower uterine segment and have a permanent cerclage in situ they need to be delivered by a classical caesarean section. This aspect should be clearly informed to the patients before posting them for RVT.

Some patients also require chemotherapy, this lowers the ovarian reserve (especially alkylating agents) and some may develop ovarian failure. The possibility of ovarian tissue cryopreservation, oocyte preservation, embryo preservation and ovarian transposition should be offered to these women prior to definitive treatment.

Thus to conclude, although the diagnosis of a gynecological malignancy can be devastating to both the patient and her family members, options of fertility preservation do exist for a selected few. These patients should be offered a multidisciplinary approach involving gynecological oncologist, reproductive endocrinologist and perinatologist.

Suggested Reading

1. Aebi S, Castigilone M. Epithelial ovarian carcinoma: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008; 19: ii14-ii16.
2. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin: Management of adenxal masses. Obstet Gynecol 2007; 110: 201-214.
3. Reed N, Millan D, Verheijen R, Castglione M. Non-epithelial ovarian cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21: v31-v36.
4. Taejong S, Chel Hun C, Hwang Shin P, Min-Kyu K, Yoo-Young L, Tae-Joong K, et al. Fertility-sparing surgery for borderline ovarian tumors: Oncologic safety and reproductive outcomes. Int J Gynecol Cancer 2011; 21: 640-646.
5. Ueda M, Ueki K, Kanemura M et al. Conservative excisional laser conisation for early invasive cervical cancer. Gynecol Oncol 2004; 95: 231-234.