242 |
D. Goldschlag |
––Estradiol level of 65 pg/mL,
––Follicle-stimulating hormone (FSH) level of 5.0 mIU/mL,
––Luteinizing hormone (LH) level of 2.9 mIU/mL,
––Anti-Mullerian hormone (AMH) level of 0.95 ng/mL.
We reviewed both the process of ovarian tissue cryopreservation (OTC) and oocyte cryopreservation (OC) along with the data regarding future pregnancy rates. Subsequent to counseling, they elected to attempt oocyte cryopreservation. Her oncologists felt that the time required for ovarian stimulation and transvaginal follicular aspiration was medically safe and would not impact upon her treatment success. The patient and her family were also set up for psychological counseling.
She was started on daily 225 IU of human menopausal gonadotropin (HMG). Daily gonadotropin-releasing hormone (GnRHa) antagonist began on day seven of ovarian stimulation. Follicular growth was assessed via transabdominal sonography and serial estradiol measurements. Gonadotropin stimulation was well tolerated by the patient. Recombinant human chorionic gonadotropin was given after 9 days of ovarian stimulation when there were two lead follicles of 18 mm. Her estradiol was 1132 pg/mL on the day of trigger.
One day prior to oocyte aspiration, she was admitted to the hospital to make sure she was hemodynamically stable for the procedure. Her complete blood count (CBC) demonstrated a hematocrit of 19% and platelet count of 15,000/mL. She was transfused with packed red cells (PRBCs) and platelets preoperatively. On the morning of oocyte aspiration, she was given an additional platelet transfusion, resulting in a preoperative platelet count of 120,000/mL.
We obtained 20 oocytes, of which 18 were mature and frozen. The postoperative examination revealed excellent hemostasis, and the patient was transferred to the recovery room. Postop CBC was stable. She was discharged postop day 1, with a hematocrit of 29.8%, and platelet count of 109,000/mL.
Discussion
Historically, it had been assumed that prepubertal patients would not respond to conventional ovarian stimulation, thus unlike adults, pediatric patients facing gonadotoxic therapy are routinely offered ovarian tissue cryopreservation (OTC). This case describes the rst ovarian stimulation and oocyte aspiration in a pediatric premenarchal patient who had not completed puberty. Though the limited numbers of live births from ovarian tissue transplantation (OTT) worldwide continue to rise, oocyte cryopreservation remains a less invasive and more ef cacious treatment modality. When the time interval between diagnosis and initiating gonadotoxic treatments is limited (<2 weeks), OTC can provide an expedient alternative.
Reproductive capabilities are infuenced by factors such as age, ovarian reserve, gonadotoxic medications, radiotherapy, medical conditions, surgical procedures, and genetics factors (POI—Table 34.1). For affected patients, providing
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
34 Fertility Preservation: Medical |
|
243 |
|
Table 34.1 Non-oncological causes of primary ovarian insuf ciency (POI) |
|
||
|
|
|
|
Surgical/Medical |
Genetic |
Autoimmune |
Hematologic |
Benign ovarian tumors |
Galactosaemia |
Systemic lupus |
Aplastic |
|
|
erythematosus (SLE) |
anemia |
Endometriosis |
Fragile X |
Behcet’s disease |
Beta- |
|
premutations (FMR 1) |
|
thalassaemia |
|
|
|
|
Infectious conditions of |
Turner’s syndrome |
Churg-Strauss syndrome |
Sickle cell |
the ovaries |
|
|
anemia |
|
|
|
|
|
|
Glomerulonephritis |
|
|
|
Wegener’s granulomatosis) |
|
|
|
Infammatory bowel diseases |
|
opportunities for fertility preservation (FP) can be critical for both preand postpubertal individuals to complete their future reproductive desires. Identifying the patient population at risk of premature ovarian insuf ciency (POI) and referring patients early on in the process is crucial in facilitating effective care.
Depending on the speci c diagnosis, individuals at risk of POI should be offered fertility preservation (FP) options such as embryo cryopreservation (EC), oocyte cryopreservation (OC), ovarian transposition (OT), ovarian tissue cryopreservation (OTC) or GnRHa administration. For example, conditions such as Turner’s Mosaics and Fragile X premutation carriers can be progressive and may eventually progress to complete ovarian failure. Similarly, surgical interventions for conditions such as endometriosis and oophoritis can lead to POI. As time lapses, the ovarian reserve continues to diminish for these individuals thereby further worsening the POI. Intervening with a preemptive FP strategy early is prudent.
Benign conditions such as autoimmune diseases like lupus and others may be treated with therapeutic regiments including alkylating agents (e.g., Cytoxan). These therapies can lead to POI secondary to their gonadotoxicity. Similarly, some non-oncological hematologic diseases are often best treated by autologous or allogeneic stem cell transplantation (SCT). Patient will be at a very high risk of POI secondary to the chemotherapies and radiotherapy that are utilized to ablate the existing bone marrow. These individuals, if medically stable, should also be offered FP options prior to gonadotoxic treatment.
Finally, oncologic diseases represent the largest group of individuals seeking FP for medical indications. These patients’ options can be further limited by the reduced time they have been permitted by their oncologist for FP treatment and the medical complexities of their disease. Cancer treatments using gonadotoxic chemotherapy and/or radiotherapy to the pelvis will diminish or eradicate the ovarian reserve. Ovarian transposition (OT) can be offered when pelvic irradiation is indicated and gonadotoxic medications are not being used. Radiation scatter and the inability to completely shield the ovaries can limit which patients may be appropriate candidates for OT.
For GnRHa, there is limited and inconsistent evidence demonstrating fertility bene ts from its effect on ovarian suppression in the presence of gonadotoxic
244 |
D. Goldschlag |
therapies. Understanding the type of chemotherapies(s) used and their dosages can help estimate the degree of diminished ovarian reserve and risk of POI.
While embryo cryopreservation has long been the gold standard for FP, improvements with vitri cation protocols have allowed oocyte cryopreservation to become an effective, viable alternative. Oocyte cryopreservation can be offered to single patients without a committed partner, lesbian couples, and those who are uncomfortable with embryo cryopreservation. For individuals for whom ovarian stimulation is contraindicated, ovarian tissue cryopreservation (OTC) offers the possibility of autologous re-transplantation of her ovarian tissue or of potential future in vitro maturation and fertilization of oocytes. Currently the number of live births worldwide postovarian tissue transplantation is less than a few hundred. OTC remains a less effective (21–23% live birth rate at age <35 live birth rate vs. 47% live birth rate with EC) but proven option for future pregnancies for patients who are unable to participate in OC or EC. OTC does not require an individual to be able to make mature oocytes nor does it require the usual 14 days needed to perform an ovarian stimulation/oocyte retrieval cycle.
In summary, fertility preservation strategies include oocyte cryopreservation, embryo cryopreservation, ovarian transposition, ovarian tissue cryopreservation, and GnRHa administration. Discussing FP options early on with both preand postmenarcheal women soon after they learn of their medical conditions will give them the greatest opportunities to evaluate their options and choose their best FP strategy. A team of fertility care practitioners including specialized care coordinators, nurses, physicians, psychologists, and nancial coordinators are needed to help patients optimize their care.
Suggested Readings
1.\ Reichman DE, Davis OK, Zaninovic N, Rosenwaks Z, Goldschlag DE. Fertility preservation using controlled ovarian hyperstimulation and oocyte cryopreservation in a premenarcheal female with myelodysplastic syndrome. Fertil Steril. 2012;98(5):1225–8.
2.\ Practice Committee of the American Society for Reproductive Medicine. Fertility preservation in patients undergoing gonadotoxic therapy or gonadectomy: a committee opinion. Fertil Steril. 2019;112(6):1022–33.
3.\ American Society of Clinical Oncology. 2018. www.asco.org/survivorship-guidelines.
4.\ ESHRE Guideline Group on female fertility preservation, Anderson RA, Amant F, Braat D, D’Angelo A, de Sousa C, Lopes S, Demeestere I, et al. ESHRE guideline: female fertility preservation. Human Reprod Open. 2020;2020(4):hoaa052.
5.\ Mulder RL, Font-Gonzalez A, Hudson MH, van Santen HM, Loeffen EAH, Burns KC, et al. Fertility preservation for female patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE consortium and the international late effects of childhood cancer guideline harmonization group. Lancet Oncol. 2021;22(2):e45–56.
6.\ Oktay K, Harvey BE, Partridge AH, Quinn GP, Reinecke J, Taylor HS, et al. Fertility preservation in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol. 2018;36(19):1994–2000.
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
Chapter 35
Menopause
Alexis Melnick
Case
A 56-year-old G2P2002 presents with a 3-year history of hot ashes and night sweats. She experiences 10–15 hot ashes each day and wakes up multiple times each night covered in sweat. These symptoms have been persistent, but stable over the last few years. Upon questioning, she states that these symptoms often interfere with her ability to perform well at work. She works as a lawyer in a busy law frm and the daily hot ashes can be unbearable when she is dressed in a suit in court. Additionally, the constant sleep interruptions often lead to her feeling sleepy throughout the day, which affects her ability to focus. She states her mood is relatively stable, though she has noticed increased irritability in the last couple years. Her symptoms are exacerbated by sweating. She used to exercise 4–5 times per week, but this has decreased to once per week due to her heat intolerance. She has gained 10 pounds in the last year.
Her last menstrual period was at age 53. Menarche was at age 12. She had regular monthly menstrual cycles throughout her 20s and 30s without dysmenorrhea. In her late 40s, she notes her menstrual cycles became shorter and more irregular. From age 50–53, intervals between her menstrual cycles then became more prolonged, lasting 60–90 days. She denies any vaginal bleeding since age 53. She reports two pregnancies at age 28 and age 31, both which resulted in uncomplicated term vaginal deliveries.
She is currently in a monogamous relationship with her husband. They have intercourse at least once per week. She denies any pain with intercourse or vaginal dryness. She is up to date on her routine health care maintenance. Her last mammogram 6 months ago was normal. Her past medical history is signifcant for
A. Melnick (*)
Reproductive Medicine and Ob/Gyn, The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University, New York, NY, USA e-mail: alm2036@med.cornell.edu
© Springer Nature Switzerland AG 2023 |
245 |
P. H. Chung, Z. Rosenwaks (eds.), Problem-Focused Reproductive Endocrinology and Infertility, Contemporary Endocrinology, https://doi.org/10.1007/978-3-031-19443-6_35
246 |
A. Melnick |
hypothyroidism and asthma. She denies any surgical history. She is prescribed levothyroxine 100 μg daily and albuterol as needed. She denies allergies to medications, tobacco or drug use, and drinks fve glasses of wine per week. Her family history is notable for a mother who had menopause at age 51 and was diagnosed with ER/PR/ HER2 negative breast cancer at age 80.
Evaluation of this patient includes:
•\ Complete patient history including: •\ Menstrual cycle history.
•\ History and frequency of menopausal symptoms (hot ushes, vaginal dryness, sleep disturbances, mood changes).
•\ Family history.
•\ Complete physical exam including:
––Vitals signs.
––BMI calculation.
––Skin and hair exam.
––Thyroid exam.
––Pelvic exam.
•\ Laboratory evaluation:
––FSH—51 mIU/mL.
––LH—38 mIU/mL.
––Estradiol—20 pg/mL.
––TSH—2.0 mIU/L.
––Complete blood counts and metabolic panel—normal. •\ Imaging evaluation:
––Transvaginal ultrasound—small uterus with 2 mm endometrial stripe and bilateral small ovaries compatible with menopause.
––Dual-energy X-ray Absorptiometry (DEXA)—no evidence of osteopenia or osteoporosis.
•\ Differential Diagnosis:
––Menopause.
––Anxiety.
––Hypoglycemia.
––Hyperthyroidism.
––Flushing related to diet.
––Carcinoid syndrome.
––Malignancy (lymphoma, renal cell carcinoma, medullary thyroid carcinoma).
––Infections (mycobacterial, bacterial, HIV, hepatitis C).
––Substance withdrawal.
––Systemic mast cell disease mastocytosis.
––Pheochromocytoma.
––Iatrogenic.
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/