Editing Infertility: Diagnosis and Evaluation (section)

== Special Scenarios ==
===Recurrent pregnancy loss===
*'''Defined as ≥2 failed pregnancies'''
**Distinct from infertility
* Most miscarriages are related to abnormalities within the fetus itself[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]
*'''Causes of recurrent miscarriages (6)'''
*#'''Genetic causes (e.g., chromosomal translocations)'''
*#'''Anatomic abnormalities of the female uterus (e.g., septum, submucosal fibroids, adhesions)'''
*#'''Infections'''
*#'''Hematologic and immunologic disorders of the female partner'''
*#'''Female partner endocrine issues (e.g., thyroid and diabetes)'''
*#'''Male factor issues'''
*#*'''Most common identified etiologic issues in males: karyotypic abnormalities and sperm DNA fragmentation.'''
*'''Diagnosis and Evaluation (3):'''
*#'''Karyotype'''
*#*Paternal structural chromosomal defects are associated with miscarriage and RPL
*#'''Sperm DNA fragmentation'''
*#*High levels of sperm DNA fragmentation are positively associated with miscarriage
*#'''Sperm aneuploidy testing'''

=== Gonadotoxic Therapies and Fertility Preservation ===

* '''Prior to commencement of gonadotoxic therapies and other cancer treatments, discuss the effects of therapy on sperm production with patients[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]'''
**Radiotherapy and chemotherapy used for cancer and other medical conditions can lead to temporary or long-term gonadal injury.
***The recovery of sperm production following radiotherapy and/or chemotherapy depends on the survival of spermatogonial stem cells in the testis.
****Radiation
*****The recovery of sperm in the ejaculate may take months to years when radiation dose > 1 Gy; dose > 10 Gy will often result in permanent azoospermia
*****Fractionated radiation (given over the course of weeks) may have a more detrimental effect on spermatogenesis than a single radiation dose
****Chemotherapy
*****Alkylating agents (e.g., procarbazine, cyclophosphamide, ifosfamide) and cisplatin target spermatogonial stem cells, and these drugs are the most likely to lead to permanent azoospermia at high doses
*****Most other chemotherapeutic agents (e.g., anthracyclines, microtubule inhibitors, antimetabolites, topoisomerase inhibitors) target differentiating germ cells in the testis (e.g., spermatids, spermatocytes, differentiating spermatogonia) and cause a transient reduction in sperm parameters with gradual recovery of sperm count observed three to six months after cessation of therapy.
******Topoisomerase II inhibitors (e.g., etoposide) are most toxic to spermatocytes with little to no toxicity to stem cells
******Doxorobucin targets differentiating spermatogonia and spermatocytes
* '''Encourage sperm banking, preferably multiple specimens when possible, prior to commencement of gonadotoxic therapy or other cancer treatment that may affect fertility[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]'''
**Couple may need to undergo several cycles of IVF treatment in order to achieve a pregnancy
**Malespresenting with cancer will generally have poorer semen parameters than normal donors, and their sperm respond less favorably to freeze-thawing (with poorer post-thaw motility) than donor sperm
*'''For azoospermic men with an intratesticular lesion, cryopreservation of testicular tissue should be considered during orchiectomy or excisional biopsy of the testicular lesion (an Onco-TESE approach)'''
*'''Inform patients undergoing a retroperitoneal lymph node dissection (RPLND) of the risk of aspermia and the availability of sperm banking prior to surgery.[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]'''
**'''Obtain a post-orgasmic urinalysis for men with aspermia after RPLND who are interested in fertility.[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]'''
***Given the distribution of the nodes involved in drainage of the testes, the lumbar sympathetic nerve fibers responsible for ejaculation (T10-L2) are in close proximity to the node dissection templates.
***'''Sympathetic nerve fiber damage, such as that which can occur during a RPLND, can result in failure of the bladder neck to contract effectively allowing semen deposited into the prostatic urethra to pass in a retrograde fashion into the bladder (i.e., RE).[https://pubmed.ncbi.nlm.nih.gov/33295257/ §]'''
***'''As with any neural trauma, maximum recovery can take 12 to 24 months and thus, patients who have had nerve sparing RPLND should be told that return of antegrade ejaculation may take a protracted period of time.''' 
****If aspermia remains 24 months after RPLND, then the patient should be informed that this is likely to be permanent.
* '''Inform patients undergoing chemotherapy and/or radiation therapy to avoid pregnancy for a period of at least 12 months after completion of treatment.[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]'''
**One of the major concerns regarding the effects of gonadotoxic therapies in males wishing to father children is the induction of mutations in developing testicular germ cells. 
***Studies have clearly demonstrated that radiation and chemotherapy can alter the genomic integrity of testicular germ cells.
****The genomic damage induced by these treatments is germ cell stage specific.
****This implies that during and for a defined period of time after exposure to radiation and/or chemotherapy (depending on the susceptible germ cell) a male can produce an increased proportion of genetically abnormal spermatozoa. Conceiving a child during this period can substantially increase the risk of genetic mutations in the offspring.
*Consider informing patients that a SA performed after gonadotoxic therapies, should be done at least 12 months (and preferably 24 months) after treatment completion.[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]
**Studies demonstrate lowest sperm concentration by 12 months and maximization of recovery in the majority of studies between 2 to 3 years after the completion of treatment[https://pubmed.ncbi.nlm.nih.gov/33295257/]
* Inform men seeking paternity who are persistently azoospermic after gonadotoxic therapies that Testicular Sperm Extraction (TESE) is a treatment option.[https://pubmed.ncbi.nlm.nih.gov/33295257/ ★]