Transition of Care

From Childhood to Adulthood in Endocrinology, Gynecology, and Diabetes

M. Polak, P. Touraine

• Publisher: S. Karger
• Year: 2018
• ISBN:
  9783318061437
• Topic: Medicine
• Subtopic: Endocrinology & Metabolism

Pediatricians face many questions and challenges during patients' transition from childhood to adulthood. Chronic diseases justify long-term medical, psychological, educational, and social management. The establishment of networks with adult endocrinologists is, therefore, very important to achieving optimal conditions for a successful transition period. In this book, leading experts discuss major public health issues such as diabetes and obesity. They also review genetic diseases, including Turner syndrome and congenital adrenal hyperplasia. All clinical cases are presented in a focused way to highlight any issues which might be discussed by the doctor with patients and family. Psychological approaches are debated as are proposals for defining specific tools to encourage autonomy during this life period. This book is a valuable tool and will be helpful in answering many questions for endocrinologists, adult and pediatric, dedicated to the long-term management of patients with chronic diseases.

Specific Illnesses

Polak M, Touraine P (eds): Transition of Care: From Childhood to Adulthood in Endocrinology, Gynecology, and Diabetes. Endocr Dev. Basel, Karger, 2018, vol 33, pp 128–148 (DOI: 10.1159/000487530)

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Fertility Preservation in Endocrine Disorders during Transition for Girls

Julie Bénard^{a, c} · Nathalie Sermondade^b · Michaël Grynberg^{a, c, d}

^aService de Médecine de la Reproduction et Préservation de la Fertilité and ^bService de Cytogénétique et Biologie de la Reproduction, Hôpital Jean-Verdier, Bondy, ^cUniversité Paris XIII, Bobigny, and ^dUnité Inserm U1133, Université Paris-Diderot, Paris, France

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Abstract

Recent advances in fertility preservation (FP) techniques have led to a wide spread of indications. FP should now be discussed not only for young girls having to receive gonadotoxic treatments for cancer, but also for those with genetic or endocrine disorders, as well as benign ovarian diseases at risk of premature ovarian insufficiency. For premenarchal girls, ovarian tissue cryopreservation is still the only available technique. Oocyte cryopreservation after ovarian stimulation could be offered to postmenarchal girls. Whenever possible, the parents and the young patient should be informed of the benefits to be expected, as well as of the risks and limits of FP for children.

© 2018 S. Karger AG, Basel

Originally developed for patients suffering from cancer, fertility preservation (FP) has rapidly invaded other medical fields and represents now the standard of care for all young patients diagnosed with diseases that could impair fertility or having to receive gonadotoxic treatments. Otherwise, recent advances in cryopreservation techniques now allow considering oocyte, embryo, or ovarian tissue freezing for female FP cases.

For a while, fertility has not been considered a priority for young girls suffering from cancer regarding the importance of the disease and the presumed high capacity of the ovaries to resume normal function. Besides, FP methods appeared dangerous and raised ethical concerns. However, even though most FP techniques remain considered experimental in prepubertal girls and adolescents, they should now be offered not only in oncological situations, but also in genetic or endocrine disorders, as well as benign ovarian diseases at risk of premature ovarian insufficiency (POI).

The present review will discuss the different techniques and strategies of FP in young girls, regarding different medical indications.

Techniques for Female FP

For prepubertal girls, cryopreservation of ovarian tissue (OTC) is theoretically the only available method. After the onset of puberty, oocyte vitrification with or without controlled ovarian stimulation (COS) represents another option.

Cryopreservation of Ovarian Tissue

This technique requires the removal of a part or an entire ovary during a laparoscopic procedure. Small fragments of ovarian cortex containing primordial follicles are frozen with the purpose of being transplanted later, either orthotopically to the pelvis (ovaries, peritoneal window) or heterotopically (subcutaneous tissue of the abdominal wall, forearm or chest wall), in order to restore endocrine and exocrine ovarian function. More than 100 natural or medically assisted pregnancies and live births have been reported worldwide, mainly after orthotopic avascular reimplantation of frozen-thawed ovarian cortex [1]. However, this method is still considered as experimental [2].

For prepubertal girls, OTC remains the technique of choice, since a large number of primordial follicles may be frozen with an optimal potential of folliculogenesis resumption. The mean duration of ovarian endocrine function after transplantation is about 5 years [3], offering a treatment of the negative effects of POI on quality of life such as osteoporosis, cardiovascular diseases, and depression. In addition, the important follicular density before puberty might allow the possibility of considering several pregnancies in a same patient.

The major issue with this technique is the important follicular loss due to the ischemic phenomenon during the freezing and thawing procedures but also before the end of the neovascularization process following the transplantation of cortical strips. As a consequence, the function of frozen-thawed ovarian tissue after grafting remains uncertain even though the higher the follicular density at the time of cryopreservation, the best are the chances of restoring optimal ovarian function and fertility.

The amount of ovarian tissue to recover (biopsies/cortical strips or whole ovary) is still debated. It may depend on the disease, the expected gonadotoxicity of treatment, the patient’s age, and the estimation of ovarian reserve. Actually, OTC automatically implies the irreversible loss of a part of the primordial follicular pool, possibly reducing the chance of spontaneous pregnancies.

Various series of OTC performed in children have been reported confirming the feasibility of the technique from a biological standpoint [4–8]. Otherwise, advances in pediatric anesthesia combined with progress in minimally invasive surgery have led to the possibility of collecting ovarian tissue routinely, even early in life. In a series of 38 prepubertal girls having undergone OTC for genetic disorders (Turner syndrome, TS; galactosemia, drepanocytosis), benign ovarian (torsion), or autoimmune diseases (rheumatoid polyarthritis), no complication was observed [8]. In only 1 patient with galactosemia showing serum follicle-stimulating hormone (FSH) levels of 18.7 IU/L were no primordial follicles counted within the ovarian tissue analyzed.

Another major concern with OTC performed in prepubertal girls is the potential of the immature tissue retrieved. Indeed, the prepubertal ovary differs significantly when compared with pathological ovarian aspects observed in adolescents and adults. Indeed, a higher proportion of abnormal nongrowing follicles has been reported in prepubertal ovaries [9]. As a result, the follicular/oocyte competence in young girls might be reduced. Only few cases of transplantations of ovarian tissue recovered before puberty have been performed. Two cases of successful ovarian endocrine production and puberty induction have been reported after grafting [10, 11]. Moreover, one pregnancy has been obtained after transplantation of ovarian tissue harvested before puberty. The girl was 13 years and 11 months old at the time of the OTC procedure. A right oophorectomy was performed before hematopoietic stem cell transplantation for homozygous sickle cell anemia [12]. Ten years later, a grafting procedure was performed, and the patient had then a spontaneous pregnancy and delivered a healthy boy.

For children at high risk of POI, OTC should be considered as early as possible whatever the pubertal status, since the follicular loss occurs quickly and ineluctably. However, partial or total oophorectomy implies de facto the reduction of half of the primordial follicle stockpile and therefore might precipitate the ovarian aging process.

Oocyte Cryopreservation after COS

The first birth attributable to the use of frozen and thawed oocytes in humans was reported almost 30 years ago [13]. Considered experimental for several decades, the emergence of vitrification freezing protocols has markedly improved oocyte survival, fertilization, and pregnancy rates [14]. Most studies have shown significantly improved postthawing survival rates with vitrification (90–95%) in comparison with slow freezing, while fertilization and pregnancy rates obtained with vitrified/warmed oocytes are similar to those reported with fresh oocytes [15]. In addition, no increase in chromosomal abnormalities or birth defects has been noted in children born from cryopreserved oocytes [16, 17]. As a result, oocyte cryopreservation is now considered an established procedure in adults and postpubertal girls [3, 18–20]. However, there is a remarkable lack of data regarding oocyte cryopreservation in postpubertal minors.

Ovarian stimulation requires exogenous FSH administration for 10–15 days aiming to produce a multifollicular growth. Indeed, administration of high doses of gonadotropins overrides the mechanism of follicle dominance and thereby achieves the growth of several large follicles up to the preovulatory stage [21]. COS is usually performed using gonadotropin-releasing hormone (GnRH) antagonist protocols until 3–4 follicles have reached 16–22 mm in diameter. Given the relative immaturity of the function of the hypothalamus-pituitary-ovarian axis in adolescents, luteinizing hormone supplementation is proposed on the day of GnRH antagonist administration, in order to allow adequate steroidogenesis. Final follicular maturation is therefore triggered using human chorionic gonadotropin or GnRH agonist administration. Thirty-six hours later, oocytes are retrieved by transvaginal ultrasound-guided aspiration of follicular fluid from mature follicles. Metaphase II oocytes obtained are frozen by vitrification. Their use will require a devitrification procedure and further in vitro fertilization (IVF).

Lavery et al. [22] reported a series of COS for oocyte vitrification conducted in teenage girls, aged 14–18 years, prior to bone marrow transplantation for sickle cell anemia. The mean dose of gonadotropin and duration of treatment were 2,134.38 IU (95% CI 1,593.34–2,675.4) and 11 days (95% CI 10.02–11.98), respectively. The mean number of oocytes retrieved was 14.88 (95% CI 7.39–22.36), among which 12.13 (95% CI 4.72–19.54) were mature and cryopreserved. One case of moderate ovarian hyperstimulation syndrome requiring hospital admission for supportive treatment was reported [22].

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Table of contents

• Cover Page
• Front Matter
• Challenges of the Transition from Pediatric Care to Care of Adults: “Say Goodbye, Say Hello”
• “Child-Adult” Transition – Adolescence: When Illness Appears…
• Transition of Care from Childhood to Adulthood: Congenital Adrenal Hyperplasia
• Transition of Care from Childhood to Adulthood: Turner Syndrome
• Growth Hormone Deficiency in the Transition Age
• Management of Hypothalamic Obesity during Transition from Childhood to Adulthood
• Transitions in Care from Pediatric to Adult Health Care Providers: Ongoing Challenges and Opportunities for Young Persons with Diabetes
• Transition of Care from Childhood to Adulthood: Congenital Hypogonadotropic Hypogonadism
• The Transition from Paediatric to Adult Care for Youths with Thyroid Diseases: Outcome Issues and Challenges
• Transition in Pediatric and Adolescent Hypogonadal Girls: Gynecological Aspects, Estrogen Replacement Therapy, and Contraception
• Fertility Preservation in Endocrine Disorders during Transition for Girls
• Fertility Preservation in Klinefelter Syndrome Patients during the Transition Period
• Author Index
• Subject Index
• Back Cover Page