• 1.
  

  a) T b) F c) T d) F e) T

Fertility preservation is offered as an option in the management of epithelial ovarian cancer in a woman who has reproductive potential and may be keen to preserve it. Although the other principles of medical ethics all have their significance in this discussion, it is the patient’s right to self-determination that is foremost in this discussion. It is, therefore, the clinician’s duty to respect the woman’s right to choose, and to empower the woman by ensuring that the she has sufficient and accurate information on which to make an informed decision about her treatment.

Although individual clinicians may have their own views on fertility preservation and may want to ‘help’ the woman in their decision-making process, it is important to remember that the woman will have to arrive at a decision that is right for her and that any intent to do good not taint this process. Although justice is always important to uphold, more important ethical principles need to be upheld to ensure that the woman makes an informed decision.

• 2.
  

  a) T b) T c) F d) T e) F

The main objective of fertility-preserving surgery is to retain the woman’s reproductive potential, which reside chiefly in the ovaries and the uterus while removing disease, with an optimal result being no visible residual tumour. Although the other surgical objectives are important in staging the disease, the prime consideration should be whether fertility can be preserved and how this should be achieved. The most common resultant procedure is a unilateral salpingo-oopherectomy, retaining the grossly normal ovary and the uterus. Retaining the uterus without the ovaries does not preserve reproductive potential. Staging procedures are carried out to be able to provide as clear a prognosis as possible for this woman in whom fertility has been preserved. The role of lymphadenectomy in epithelial ovarian cancer grossly confined to the ovaries is to determine if there is occult stage III disease; the procedure itself does not improve outcomes.

• 3.
  

  a) F b) F c) T d) T e) F

The International Federation of Gynecology and Obstetrics (FIGO) stage I disease with risk factors (in this case, clear cell histology) would suggest that adjuvant chemotherapy might be necessary, not a total hysterectomy and bilateral salpingo-oopherectomy. Fertility preservation is still possible and should be pursued as discussed with the woman. Every effort should be made to preserve the woman’s reproductive potential; as such, wedge biopsies of grossly normal ovaries are discouraged as this may affect ovarian function. As complete a staging procedure should be carried out as soon as possible while preserving reproductive potential. Accurate staging results in an accurate prognosis and the appropriate adjuvant treatments to ensure favourable cancer and reproductive outcomes. Ovarian and uterine preservation are key end points in fertility preservation.

• 4.
  

  a) F b) F c) T d) F e) F

Cytogenetic testing may definitively answer the question of whether there are chromosomal abnormalities in this pregnancy, but will unlikely definitively answer the question of whether congenital anomalies are present. No data are available to suggest that fertility-preserving surgery and adjuvant chemotherapy result in an increased risk of congenital anomalies in subsequent pregnancies. The most appropriate next step is to be sure that this is reinforced with the woman and that she understands the low likelihood of congenital anomalies. Being empowered with this information, if she opts to proceed with cytogenetic testing, she is making an informed decision, balancing the low risk of congenital anomalies against the risk of procedure-related fetal loss. Termination of pregnancies after the effort and ‘risk’ of fertility preservation should not be undertaken lightly. This should be an informed decision arrived at by a patient with the support of her women’s cancer-care provider. Genetic counselling may be useful but is unlikely to be useful as a ‘next most appropriate step’, which is for the woman to understand from her primary women’s cancer-care provider that her risk of congenital anomalies in this pregnancy are low.

• 5.
  

  a) T b) T c) F d) T e) T

In the first two decades of life, almost 70% of ovarian tumours are of germ-cell origin. Two-thirds of ovarian germ-cell tumours in the first 2 decades of life are benign germ-cell tumours, mainly mature cystic teratomas. Pre-operative tumour markers, in a young women with suspected ovarian malignancy, should include serum alpha-fetoprotein (AFP), lactate dehydrogenase, beta human chorionic gonadotropin (β-hCG) and cancer antigen 125 titers. Yolk-sac tumour and ovarian choriocarcinoma produce AFP and β-hCG, respectively. Both embryonal carcinoma and polyembryoma may produce β-hCG and AFP. Some dysgerminomas may display elevated levels of lactate dehydrogenase or low levels of β-hCG related to the presence of multinucleated syncytiotrophoblastic giant cells. Most immature teratomas are marker negative, although some may produce AFP. Mixed germ-cell tumors may produce any of the tumour markers, or none, depending on the type and quantity of elements present.

• 6.
  

  a) F b) T c) F d) T e) T

MOGCTs are almost always unilateral, except pure dysgerminomas, which may be bilateral in 10–20% of cases. Bilateral involvement may also occur in cases of advanced MOGCT, in which there is metastasis from one ovary to the other. Benign cystic teratomas are found on the contralateral ovary in 5–10% of women with MOGCTs. Fertility preservation should be a priority in young women as long as there is no suspicion of dysgenetic gonads. Intra-operative frozen section is useful but, if this is not available, as much normal ovarian tissue should be conserved as possible and further decisions can be made once the final histopathology is confirmed. Bilateral ovarian cystectomies should be attempted in an effort to preserve fertility whenever feasible. The affected ovary may then be resected completely once the malignant side is confirmed on intraoperative frozen section. In the rare event of bilateral involvement, bilateral ovarian cystectomy is an attractive option especially when combined with adjuvant chemotherapy, although this surgical option has not been well studied.

• 7.
  

  a) F b) T c) T d) T e) F

The observed histologic changes in the ovaries of women receiving chemotherapy include cortical fibrosis, reduction in number of follicles and impaired follicular maturation. These changes lead to increased serum gonadotropins and a decrease in serum oestradiol. Owing to the histological changes, chemotherapy can cause oligo-amenorrhoea but, of course, factors such as cumulative drug dose, duration of treatment, and age at treatment have been reported as influencing the incidence of ovarian dysfunction in adult women. Fertility rates in women after conservative surgery and chemotherapy for MOGCT are not affected and will approximate those of the normal population, with an incidence of about 10–20%. There is no significantly increased risk of fetal chromosomal or structural anomalies in the pregnancies of women after undergoing chemotherapy for MOGCT.

• 8.
  

  a) F b) F c) T d) T e) F

If uterine evacuation causes heavy bleeding, oxytocic agent can be given. In the USA, some even recommend oxytocin infusion at the start of the procedure. Medical abortion can occasionally be considered in partial mole at second trimester, as the fetal parts may obstruct the evacuation. Data from the New England Trophoblastic Disease Center showed that the overall viable pregnancy rate is up to 75% with no detectable fetal abnormalities. This risk is 10–20 times higher than the background risk. One study showed that the risk of GTN in singleton molar pregnancies after ovulation induction was 15%, similar to the risk in those molar pregnancies with natural conception. Another retrospective study showed that incidence of fertility treatment requirement was the same among those with molar pregnancies with and without subsequent need of chemotherapy.

• 9.
  

  a) T b) F c) F d) T e) T

This is one of the diagnostic criteria set by the International Federation of Obstetrics and Gynecology (FIGO). Although one study from the UK showed that 60% of such women did not require chemotherapy after a second evacuation, a Dutch study showed that only 9% of women could be cured by evacuation alone. Additionally, this approach is not commonly practised in the USA. Hysterectomy can eliminate the risk of myometrial invasion but not distant metastasis. One report showed that these women might have a higher incidence of abnormal pregnancies, including miscarriage, stillbirth and repeated moles, than those who conceive more than 12 months later (37.5% v 10.5%; P = 0.14). A retrospective controlled survey showed that women receiving chemotherapy (median 50, range 25–56 years) had the menopause 3 years earlier than those who had not received chemotherapy (median 53, range 40–57 years) (Log-rank χ ² test = 12.6; P = 0.0004).

• 10.
  

  a) F b) F c) T d) T e) T

The reported term delivery rate was 77–79% and the miscarriage rate was 7–9%. Only a few case reports have been published on fertility-sparing surgery in PSTT, and the successful rate is 4 out of 6. ETT and PSTT are not chemo-sensitive, despite few studies on the use of combined chemotherapy in PSTT. A Japanese study reported an 8.8% (three out of 34 term births) incidence rate of congenital heart abnormalities, which was higher than the background risk (0.7–1%) in the general population. Use of uterine artery embolisation to control heavy bleeding, with successful pregnancies afterwards, have been reported.

• 11.
  

  a) T b) F c) T d) T e) T

Although the recommendation of terminating pregnancy if the woman is in early gestation is based on general consensus, this dogma has been challenged by several reports over the past two decades. Duggan et al., reported a mean diagnosis to treatment interval of 144 days (range 53–212 days) in eight women with stage IA or IB who requested for postponement of treatment until delivery. All these women were disease free at the third year of follow up. Sorosky et al. observed eight women with stage IB squamous cell carcinoma of the cervix prospectively until the third trimester, with a mean diagnosis to treatment interval of 109 days (range 21–210 days). No clinical progression of disease was reported, and all women were alive and disease free after mean follow-up of 37 months. Most authorities do not recommend waiting for more than 4–8 weeks before definitive treatment. The oncological outcome for radical trachelectomy has been shown to be as good as radical hysterectomy by several investigators, and in this woman who is young and has requested preservation of fertility, radical hysterectomy would be an inappropriate option. This is general advice for all young women with gynaecological cancer who have had fertility-sparing surgery, as the next time the cancer recurs the woman may need to have her reproductive organs removed.

• 12.
  

  a) F b) F c) T d) T e) F

Computed tomography scans are generally contraindicated in pregnancy because of the hazards of the radiation of the scans. If the clinical examination and the ultrasound do not show any obvious evidence of advanced or metastatic disease, such as ascites, peritoneal nodules, liver metastases, the metastatic assessment can await the exploratory laparotomy. If the findings are equivocal, magnetic resonance imaging is useful and safe in pregnancy. Analysis of tumour markers in pregnancy is complex and often misleading because the titres of each of these markers are routinely elevated in pregnancy for reasons unrelated to malignancy. Laparotomy during pregnancy is preferably not carried out in the first trimester as it leads to higher risk of miscarriage. This is even more so if the ovarian mass turns out be a corpus luteum cyst (which can appear as a complex mass on ultrasound, and mistaken for malignancy). Luteo-placental shift occurs at about 10–11 weeks and then it becomes safer to remove adnexal masses. A midline laparotomy is essential, instead of the more commonly used transverse incisions, as it allows a more thorough exploration of the entire abdominal cavity, enabling accurate surgical staging of the disease. The frozen section allows the surgeon to decide on further management. If the result is benign, no further action is necessary. If it is malignant, the surgeon should proceed with the appropriate surgery. If the result of the frozen section shows a well-differentiated, non-clear-cell carcinoma, and the exploration of the abdominal cavity does not show any evidence of metastatic disease, she most likely has stage IA disease. It is, then, sufficient to take washings of the peritoneal cavity, an infra colic omentectomy and, if possible, ipsilateral pelvic lymphadenectomy (avoid manipulating the uterus too much) should be sufficient treatment, sparing her fertility.

• 13.
  

  a) T b) F c) F d) F e) F

The gonadotoxicity is highest for cyclophosphamide, an alkylating agent, and lowest for vinblastin.

• 14.
  

  a) F b) T c) F d) F e) F

Cryopreservation of ovarian tissue is safe but the possible existence of malignant cells in the ovaries of women with leukaemia, Hodgkin’s lymphoma, and Ewing’s sarcoma have been reported.

• 15.
  

  a) T b) F c) T d) T e) T

Only b is incorrect as less than 20 neonates have been reported with this investigational method.

• 16.
  

  a) T b) F c) F d) F e) F

In Hodgkin’s lymphoma, the gonadotoxicity decreases in the following order: escalated BEACOPP, BEACOPP, ABVD. All the other answers are incorrect.

• 17.
  

  a) T b) T c) T d) T e) T

Cryopreservation of embryos is the most established option for preserving fertility, and this procedure is undertaken routinely for fertility treatment at reproductive centres. Women with a partner, and single women willing to use a sperm donor, may be offered embryo freezing, provided that sufficient time is allowed for gonadotropin stimulation before egg retrieval. Cryopreservation of oocytes also requires time for gonadotropin stimulation. Freezing unfertilised eggs is typically offered to women without a partner or to those who do not wish to use a donor because of religious or ethical concerns. In some countries, single women may not be permitted to be treated with donor sperm. Current advances in cryopreservation of oocytes with the use of vitrification have increased survival after thawing, and fertilisation success rates approach those obtained with fresh eggs. When no time is available for stimulation treatment, or it is not desired, cryopreservation of ovarian tissue is the only option that can be offered. Although there is individual variation, a 29-year old woman with an average ovarian reserve should have high follicle counts in her ovaries, and many of those follicles could be preserved through freezing of her ovarian cortex.

• 18.
  

  a) F b) T c) T d) F e) F

A good ovarian reserve is a prerequisite for ovarian tissue cryopreservation, and is a real option for preserving fertility. This method can be offered to pre-pubertal girls, adolescents and young women of fertile age. For a pre-pubertal girl, this is the only option for preserving fertility. The benefit of ovarian tissue cryopreservation for women older than 40 years of age is very uncertain because of their age-related reduced ovarian reserve. Young women and children may benefit from cryopreservation of ovarian tissue also after chemotherapy because of their high counts of follicles in their ovaries.

• 19.
  

  a) F b) T c) F d) F e) T

Auto-transplantation of the ovarian tissue aimed at recovering fertility is contraindicated if the presence of malignant cells in the graft is suspected. Theoretically, in Hodgkin’s disease, sarcomas, and non-metastatic breast cancer, there is a low risk of ovarian involvement. At present, women being cured from Hodgkin’s and non-Hodgkin’s lymphoma, breast cancer, Ewing sarcoma and a neuroectodermic tumour have regained fertility through autotransplantation, and cancer recurrence has not been reported. Before each ovarian cortical transplant, a sample of tissue should be histologically examined, even though this does not guarantee the absence of malignant cells in the remaining ovarian tissue. The methods for detecting cancer cells in the ovarian tissue of women having had systemic haematological malignancies are still under development. The transplantation of ovarian tissue is still experimental and should only be undertaken under institutional review board research protocols.

• 20.
  

  a) F b) T c) F d) F e) T

Criteria for carrying out a radical trachelectomy include an invasive cervical cancer of 2 cm or less limited to the cervix in a young women desiring fertility preservation. Because of tumour volume, this woman is not a good candidate for a radical trachelectomy. To carry out a radical trachelectomy, there must be no evidence of pelvic lymph-node metastases or other distant metastases. The rate of postoperative complications is similar for both procedures, and the most frequent complication is urinary retention. In the abdominal approach, the uterine artery is divided at its origin from the internal iliac artery. In the vaginal approach, the upper branch is preserved.

• 21.
  

  a) F b) T c) T d) F e) F

Subfertility occurs in about 20–30% of women who have undergone radical trachelectomy, and is related in most cases to cervical factors, such as cervical stenosis, decreased cervical mucus, surgical adhesion formation, and sub-clinical salpingitis. Preterm delivery occurs in about 30% of women but significant prematurity occurs in only 12% of women. There is no established time to wait for pregnancy after surgery. Some investigators recommend 6 months, others 1 year. Because of the risk of cervical incompetence, obstetric visits should be scheduled more frequently.

• 22.
  

  a) F b) T c) F d) T e) F

This rate is as high as 90% in cases of brachytherapy alone. The peritoneum must be dissected carefully in order to preserve the vascular supply and prevent any kinking after transposition. In order to mobilise the ovaries completely, the dissection of the ovarian vessels must be take place up to the level of the aortic bifurcation. In a large study (grade 1 stage 1A endometrial carcinoma without extra-uterine disease), Lee et al. reported a low rate of occult ovarian tumour (1%), synchrone or metachrone disease, if macroscopic evaluation of ovary was normal. Endometrial cancer associated with Lynch syndrome represents between 2 and 5% of endometrial cancer and around 10% of endometrial cancer diagnosed before the age of 50 years.

• 23.
  

  a) F b) F c) F d) F e) F

Only one small study involving six women has been reported. All resections were in women with a hysteroscopically localised lesion, and the surgery was followed by progestogen therapy. The use of a progesterone-coated device alone in the management of this condition remains experimental. Ideally, oral agents should be used, as experience with them is much greater and the data on their efficacy more robust. The length of treatment for premenopausal women using oral progestogen therapy remains problematic. Most investigators resample the endometrium after 3 months, but cases of reversal taking up to 9 months have been reported, so resampling the endometrium at 6 and 9 months in the absence of symptoms and with full consent is an option.

Although the use of metformin is attractive in this population with such a high incidence of polycystic ovarian syndrome, it remains unproven. Similarly, most women with endometrial cancer in their early 40s are overweight but weight loss as a strategy, though attractive, needs proper assessment.

• 24.
  

  a) F b) F c) F d) T e) F

Radical vaginal trachelectomy is an option with laparoscopic pelvic-node dissection. Future developments with molecular imaging or sentinel-node identification may render pelvic-node dissection unnecessary in some cases. In time, a large cone biopsy, with or without pelvic-node dissection, will become a further option. Age is no bar to fertility-sparing surgery provided that there is a realistic chance of future conception. Squamous cell lesions confined to the lower half of the cervix may have the upper 0.5–1 cm of the endocervical canal and cervical stroma conserved, provided that an adequate clearance and clear margin of up to 1 cm is obtained. This will reduce the risk of complete incompetence of the cervix and retain some cervical bacterio-static mucous. Well-selected cases may undergo fertility-sparing surgery with no increased risk of recurrence. Recurrence rates in such cases are currently 4%, with a 2% death rate.

• 25.
  

  a) F b) F c) F d) T e) T

She should wait 6–12 months for a clear MRI scan, isthmic and vaginal vault smear and colposcopy. The vagino–isthmic anastomosis also has to heal adequately. She should continue with cytology as for any cervical cancer treated by cone biopsy, especially if a cuff of the upper cervix is retained. Metaplasia of any remaining endocervical tissue will occur so, even after the risk of recurrence is passed, routine screening should continue in the future. She should be carefully monitored as radical vaginal trachelectomy is a relatively new method of treatment and requires follow up with MRI scans initially for 2 years, and the taking of isthmic smears may be difficult, requiring the skills of a specialist gynaecologist. Although most recurrences after cervical cancer occur within 2 years, a number have occurred after radical vaginal trachelectomy up to 9 and 10 years. Smears may be misinterpreted as the endometrial cells may confusing the picture and metaplasia-interpreted as atypia.

• 26.
  

  a) F b) F c) F d) F e) T

She is at risk of spontaneous rupture of the membranes, especially in the mid-trimester owing to ascending chorioamniotis. Consideration should be given to either prophylactic antibiotics at 16 and 24 weeks or regular sterile swabs being taken for culture. There is a risk of precipitate labour and delivery in the absence of a competent internal orifice. This is unknown territory with little obstetric experience of this management after radical vaginal trachelectomy. Caution dictates a planned elective classical caesarean section, either at 36–38 weeks or with the onset of labour.

Should labour ensue, she would risk uterine rupture owing to the isthmic cerclage not allowing dilatation to occur. There is a limited lower segment and therefore the risk of a transverse incision extending causing catastrophic haemorrhage.

• 27.
  

  a) F b) F c) T d) T e) F

Cervical cancer has only decreased in incidence and as a cause of death in developed countries with an established screening programme. Early stage disease in these privileged countries is proportionately increasing in young women with a need for fertility conservation when childbearing has been postponed. The squamous cancers are more readily detected on the ectocervix and lower endocervical canal. A disproportionate number of glandular tumours arising higher within the endocervical canal maybe missed on routine cytology. Human papillomavirus testing in the future may help detect women and tumours at risk. A monogamous relationship does not mean that both partners have been monogamous throughout their lives; HPV, the accepted cause of cervical cancer, may be transmitted even with only one exposure.

Screening on a population basis or by individual request should be aimed at detecting precancerous cervical intraepithelial neoplasia within the 10 years after initial exposure to HPV (coitarche) and the risk of developing cervical intraepithelial neoplasia commencing. Fifty per cent of girls are estimated to have had coitus by the age of 15, more in certain parts of the world, so screening should commence before an invasive cancer has developed (i.e. within 10 years of coitarche). Hence, starting screening between the ages of 20 and 25 years is common sense. The current UK policy of starting at 25 is controversial.

• 28.
  

  a) F b) F c) T d) F e) F

One third of borderline tumours affect women of reproductive age leading to difficulties in optimal management.

• 29.
  

  a) F b) F c) F d) F e) T

There is no good evidence of benefit for any adjuvant therapy in advanced stage disease.

• 30.
  

  a) T b) F c) F d) F e) F

Only BRAF and KRAS are associated with this histological type of tumour.