Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers.

STUDY QUESTION: Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized processing/freezing for centers that do not have those capabilities? SUMMARY ANSWER: Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice. WHAT IS KNOWN ALREADY: Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring. STUDY DESIGN, SIZE, DURATION: Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient's tissue was donated to research and 75% was stored for patient's future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of fertility preservation patients was 7.9 (SD = 5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD = 837.3) mg and ranged from 14.4 mg-6880.2 mg. Malignancies (n = 118) were the most common indication for testicular tissue freezing, followed by blood disorders (n = 45) and other conditions (n = 26). Thirty nine percent (n = 74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size. WIDER IMPLICATIONS OF THE FINDINGS: Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested. STUDY FUNDING/COMPETING INTEREST(S): Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.

Maternal screening for hypothyroidism and thyroiditis using filter paper specimens.

BACKGROUND AND OBJECTIVE: Hypothyroidism and autoimmune thyroiditis are more prevalent than previously considered in women during pregnancy and the postpartum, and are associated with adverse effects on the mother and her fetus. We determined the efficacy and accuracy of screening women for primary hypothyroidism and autoimmune thyroiditis by testing TSH and two thyroid antibodies (TAb): thyroperoxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), in eluates of filter paper specimens collected during early pregnancy and the postpartum. METHODS: We enrolled 494 first-trimester pregnant women with no exclusion criteria into a prospective study to detect primary hypothyroidism and autoimmune thyroiditis. Finger stick blood was applied to filter paper, dried in room air, eluted, and promptly tested for TSH and TAb. A total of 178 of the pregnant women (36%) were tested in the early postpartum. Women with abnormal results had confirmatory serum tests. RESULTS: It was found that 91 pregnant women (18.4%) and 43 postpartum women (24.2%) had abnormal TSH values (>4.0 mU/L) and/or positive TAb; 140 pregnant women (28.3%) had TSH values >2.5 mU/L. All subjects with TSH values >4.0 mU/L tested positive for TAb. Eighteen women (3.6%) who tested normal during pregnancy tested abnormal in the postpartum. CONCLUSIONS: This study confirms that TSH and TPOAb measured in eluates of blood-spotted filter paper specimens are excellent screening tests to detect primary hypothyroidism and autoimmune thyroiditis in pregnant and postpartum women. Results are very comparable to serum data in this population published in the literature.

Treatment of endometriosis: a hormonal approach.

Endometriosis continues to plague women of reproductive age. It is a chronic disease leading to a decreased quality of life, infertility, and increased societal costs. The gold standard for diagnosis remains visualization and or biopsy of lesions at the time of intraoperative diagnosis, i.e. laparoscopy or laparotomy. The severity of pain does not correlate with the stage of endometriosis, which complicates the treatment process. Hormonal therapies have long been used as a treatment for endometriosis. Therapy is targeted at symptom relief as a cure is lacking. While some regimes use hormonal therapy exclusively, others combine such with surgical excision of lesions. Although hormonal modalities are successful in alleviating or suppressing symptoms, they fail to treat the infertility associated with endometriosis. Therefore, those, desiring to achieve pregnancy should be excluded from hormonal treatment in the short term. Future studies are needed to understand the pathophysiology and allow design of specific, targeted treatment.

Is there a seasonal variation in gonorrhea and chlamydia in adolescents?

STUDY OBJECTIVE: To determine if a seasonal variation exists in gonorrhea and chlamydia in female adolescents. DESIGN, SETTING, PARTICIPASNTS: We conducted a retrospective chart review of 604 sexually active adolescent females 21 years of age and younger in a teen pregnancy prevention clinic in a small Midwestern city. Positive gonorrhea and chlamydia tests were evaluated for seasonal variation. Chi-square, odds ratios, and 95% confidence intervals were calculated. RESULTS: A greater percentage of tests were positive in the fall than in other seasons (P = 0.028), and there was a trend towards more cases in the summer than winter and spring. CONCLUSIONS: Increased emphasis should be placed on prevention and screening during summer and fall.

Correlation between glycemic control and menstruation in diabetic adolescents.

OBJECTIVE: To determine if a correlation exists between the degree of glycemic control in insulin-dependent diabetic adolescents and menstrual regulation. STUDY DESIGN: A retrospective review of charts of diabetic girls aged 10-18 was performed. Office visits were scheduled every three to six months, at which time pubertal development, menstrual function, growth and diabetic control, including hemoglobin (Hgb) A1C, and complications were assessed. Forty-six patients were eligible for data analysis. Descriptive and inferential statistics, including chi 2 and Student t tests, were applied. RESULTS: Thirty-seven (81%) patients had regular menstrual cycles, and nine (19%) had menstrual disturbances, including secondary amenorrhea (one), oligomenorrhea (seven) and primary amenorrhea followed by oligomenorrhea (one). There were two pregnancies. Six patients used hormonal contraception but none for menstrual regulation. There was a statistically significant difference (P < .05) in mean Hgb A1C concentrations between those with menstrual disturbances (11.4) and those with regular menses (9.7). As Hgb A1C values increased, the percent of patients with menstrual disturbances increased, becoming statistically significant when the Hgb A1C was > 10 (odds ratio 7.3, 95% confidence interval 1.5-35.6). There was no difference (P > .05) between the two groups with respect to age at menarche (156 vs. 152 months), age at onset of diabetes (144 vs. 108 months) and interval between diabetes onset and menarche (54 vs. 41 months). There were no patients in either group with diabetic retinopathy or nephropathy. Four patients were hypertensive, but there was no statistically significant difference (P > .05) between groups. CONCLUSION: Tighter glycemic control, as measured by Hgb A1C concentrations, corresponded to improved menstrual regulation in adolescent insulin-dependent diabetics.

Alterations in humoral immune responses associated with recurrent pregnancy loss.

OBJECTIVE: To investigate the reactivity of maternal antibodies with endometrium-derived antigens and to correlate their association with recurrent pregnancy loss (RPL). DESIGN: Prevalence study. SETTING: Academic research center. PATIENT(S): Nulliparous women (n = 10), women with RPL (n = 15), pregnant women (n = 8), and multiparous women with a normal obstetric history (n = 20). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Reactive antibodies were analyzed by Western immunoblot techniques and quantitated by densitometry. RESULT(S): Antibodies from women with RPL and multiparous women recognized antigens ranging from 10-120 kd on normal endometrium and endometrial tumors. Antibodies from most women with RPL (10/15) and from multiparous women (15/20) recognized 65-kd and 80-kd proteins in normal endometrium. Antibodies from women with RPL recognized 21-kd and 28-kd antigens (12/15 and 13/15, respectively) in endometrial tumors at a significantly greater rate (than did antibodies from multiparous women (5/20 and 8/20, respectively). Women with RPL had significantly lower levels of asymmetric IgG compared with controls. CONCLUSION(S): Recurrent pregnancy loss may be linked with the failure to elicit asymmetric IgG and a unique immunologic recognition of endometrial antigens.

Dysmenorrhea and pelvic pain in adolescents.

Dysmenorrhea and pelvic pain are common complaints in the adolescent population. Although most cases are primary dysmenorrhea and easily treated with NSAIDs or OCPs, pathologic causes should be considered, especially in cases not responding to standard medical management. Endometriosis is the most common finding in teenagers who do not respond to this regimen, but müllerian anomalies and musculoskeletal causes must also be considered.

Emergency contraception: lack of awareness among patients presenting for pregnancy termination.

STUDY OBJECTIVE: Emergency contraception, otherwise known as postcoital contraception, refers to a group of birth control modalities that, when used after unprotected intercourse within defined time constraints, can markedly reduce the risk of a resultant unintended pregnancy. The English literature, using British and American awareness data, consistently claims that these contraceptive options are underutilized in the United States because of a lack of patient and physician awareness of their existence. The objective of this study was to determine the level of awareness of postcoital contraceptive techniques in a population of American women who were presenting for pregnancy termination. The secondary goal was to calculate (theoretically) how many of these surgical terminations could have been prevented through the use of postcoital contraception. METHODS: A questionnaire was administered to patients presenting to an abortion clinic. It was intended to anonymously identify patient demographics and knowledge of the various emergency contraceptive options and, in hindsight, to determine what percentage of these women would have been willing candidates for one of these medical modalities. On completing the questionnaire, all patients received an emergency contraceptive information sheet for future consideration. RESULTS: Eighty-three patients completed the study. They ranged in age from 15 to 44 years (mean, 24 years). Forty-six percent of the patients were 21 years of age or younger. A total of 71% of all patients had no real knowledge of the existence of emergency contraceptive options; 26% had some limited knowledge, and only 3% had somewhat complete and valuable information. Fifty-one percent of the patients would have been appropriate, realistic, and willing candidates for at least the emergency contraceptive pill. Assuming at least a 75% effectiveness rate for the emergency contraceptive pill, 38% of the surgical pregnancy terminations performed on this population of women could have been avoided. CONCLUSION: Our data confirm that emergency contraceptive options are underutilized because of a lack of patient awareness. Contraception education, especially directed toward adolescents, should include disseminating enhanced information about postcoital contraception options.

Implications of not treating hyperprolactinemia.

When a patient with hyperprolactinemia is not treated, a number of ramifications can result, the most significant of which is osteoporosis. Evidence-based analysis shows that bone mineralization also can be affected by such problems as gonadal dysgenesis and possibly adrenal dysfunction. The hypoestrogenism associated with hyperprolactinemia is commonly assumed to be a potential cause of osteopenia in premenopausal women with this disorder, just as decreased estrogen is associated with bone loss following menopause. A number of studies also have shown that hyperprolactinemia decreases bone density independently of the hypoestrogenic state. In most, but not all, such women, bone density may be reestablished if one is successful in restoring normal menstrual function with dopamine agonists. With the availability of safe dopamine agonists like bromocriptine and now cabergoline, it seems prudent to attempt to normalize serum prolactin levels early on, before long-term pathologies set in.

Laparoscopic surgery in girls and female adolescents.

The realm of laparoscopic surgery has extended to include the neonate as well as the pediatric patient. The advent of new and smaller instrumentation has facilitated this goal. Previous procedures exclusively relegated to laparotomy can now be accomplished as outpatient procedures. Removal of the acute appendix, correction of torsion of an adnexa, as well as the appropriate diagnosis and initial treatment of acute pelvic inflammatory disease are now well established laparoscopic procedures. This article provides insight into the laparoscopic evaluation and management of a number of challenging clinical problems for the endoscopic surgeon, thus providing a minimally invasive approach for patients ranging from neonates to adults.