syndrome: a single center retrospective study of 21 cases and 114 cycles. Semin. Arthritis Rheum. 2002; 32: 174–88.
13 13 Orquevaux P, Masseau A, Le Guern V, Gayet V, Vauthier D, Guettrot‐Imbert G, et al. in vitro Fertilization in 37 Women with Systemic Lupus Erythematosus or Antiphospholipid Syndrome: A Series of 97 Procedures. J. Rheumatol. 2017; 44(5): 613–8.
14 14 Petri M, Kim MY, Kalunian KC, Grossman J, Hahn BH, Sammaritano LR, et al. Combined oral contraceptives in women with systemic lupus erythematosus. N. Engl. J. Med. 2005; 353: 2550e2558.
15 15 Brito‐Zerón P, Izmirly PM, Ramos‐Casals M, Buyon JP, Khamashta MA. The clinical spectrum of autoimmune congenital heart block. Nat. Rev. Rheumatol. 2015; 11: 301–12.
16 16 Bundhun PK, Soogund MZ, Huang F. Impact of systemic lupus erythematosus on maternal and fetal outcomes following pregnancy: a meta‐analysis of studies published between years 2001–2016. J. Autoimmun. 2017; 79: 17–27.
10 The patient with malignant disease: fertility preservation
Arri Coomarasamy and Manal Elgendy
University of Birmingham and Birmingham Women’s Hospital, Birmingham, UK
Case History 1: A 32‐year‐old woman has been diagnosed with estrogen positive stage 2 breast cancer. Her oncology team’s recommendation is lumpectomy with axillary node clearance, chemotherapy and radiotherapy. She is married but has no children; the couple wish to preserve fertility.
Case History 2: A 14‐year‐old girl is diagnosed to have acute myeloid leukemia. Her menarche was at the age of 11 years. She and her parents are keen to save her fertility.
Case History 3: A 29‐year‐old man was diagnosed to have testicular seminoma, for which he has been recommended to have right orchidectomy, followed by chemotherapy. He has no children and is anxious not to lose his ability to have children. A seminal fluid analysis is normal.
Background
Most young cancer patients are cured or have long survival as a result of unprecedented advances in oncology in recent decades. For instance, 80% of patients with leukemia, the most common pediatric cancer, are expected to be cured. Thus, the concern is no longer only on saving lives, but also on ensuring improved quality of life. Given that fertility‐related psychological distress is prevalent and persistent in cancer patients and survivors [1], they should routinely be given the opportunity to speak with a fertility specialist and thoroughly explore all fertility preservation options available to them.
The most common cancer in women of reproductive age is breast cancer; other cancers of note in this age group are leukemia, lymphoma, melanoma, cervical and ovarian cancers. The type of cancer, its stage, biologic features and patient factors influence prognosis and treatment. Treatment may be one or a combination of surgery, chemotherapy, radiotherapy and hormonal treatment. Chemotherapy, particularly with alkylating agents such as cyclophosphamide, is highly toxic to the primordial follicles in the ovary. The extent of the effect of chemotherapy on ovarian reserve will depend on the drug(s) used, dosage, age and the baseline ovarian reserve of the patient. Radiotherapy, particularly if directed to the pelvis, can adversely affect ovarian reserve. A 2019 review of articles on the risks of cancer treatments to fertility demonstrated that pelvic radiation of 5–10 Gy causes 25–75% increase in the risk of infertility and >10 Gy causes >75% increase [2]. The exposure required to induce ovarian failure and infertility decreases with increasing age. Radiation as low as 1 Gy was found to be associated with increased risk of premature menopause [3].
There are two key aspects to fertility preservation:
1 Minimization of the effect of cancer treatment on fertility; and
2 Provision of effective options for storage of gametes, embryos or germinal (e.g. ovarian) tissues.
Management options
Management of cancer patients requiring fertility preservation is often complex; navigation through the complexities and uncertainties will require a multidisciplinary team approach and thorough counseling of the patient, and often the partner too. The following issues will need to be assessed by the fertility specialist:
1 History: including age, menstrual history, pregnancies and fertility wishes.
2 Cancer: type, location, stage, prognosis and proposed treatment.
3 Time available for fertility preservation.
4 Patient’s general condition and medical history.
5 Baseline ovarian reserve (anti‐Müllerian hormone and antral follicle count).
6 Fertility preservation funding.
The available fertility preservation options are given in Table 10.1.
Table 10.1 Fertility preservation options according to gender and age at cancer presentation.
| Group | Fertility preservation options | Comments |
|---|---|---|
| Prepubertal girls | Laparoscopic removal and cryopreservation of ovarian tissue for transplantation when fertility is required | Transplantation carries a theoretical risk of reintroduction of cancer cells IVM may become a viable option in the future Consenting issues in minors |
| Postpubertal girls | COS, and preservation of oocytes Ovarian tissue cryopreservation for transplantation when fertility is required. GnRH agonist co‐treatment during chemotherapy | COS introduces delay in cancer treatment |
| Women | COS, and preservation of oocytes or embryos. Ovarian tissue cryopreservation for transplantation when fertility is required. GnRH agonist co‐treatment during chemotherapy | Sperm required for the creation of embryos If the male withdraws consent in the future, the woman is unlikely to be able to use the embryos (see Chapter 108) |
| Prepubertal boys | No established procedures | Experimental: stem cell extraction and later repopulation of the testis |
| Postpubertal boys | Electro‐ejaculation or masturbatory ejaculation and sperm banking SSR and sperm banking | Consenting issues in minors |
| Men | Ejaculatory sperm banking SSR and sperm banking (see Chapter 91) |
COS, controlled ovarian stimulation; GnRH, gonadotropin releasing hormone; IVM, in vitro maturation; SSR, surgical sperm retrieval.
Ovarian tissue cryopreservation (OTC)
Cryopreservation of ovarian cortex may be the only fertility preservation option in prepubertal girls or in women who need cancer treatment within the minimum of 2 weeks required for controlled ovarian stimulation. OTC has been used to enable multiple ovulations and pregnancies in the future as well as for restoration of endocrine function [4]. With more than 130 babies born