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Biomedical subjects

Richard H Reindollar

Publications and source records attributed to Richard H Reindollar.

12 recordsLinked to original sources
PubMed2007

A mutation in the fibroblast growth factor receptor 1 gene causes fully penetrant normosmic isolated hypogonadotropic hypogonadism.

CONTEXT: Kallmann syndrome (KS) consists of idiopathic hypogonadotropic hypogonadism (IHH) and anosmia/hyposmia. Currently, the fibroblast growth factor receptor 1 (FGFR1) gene is the only known autosomal dominant cause of KS, which is also associated with synkinesia, midfacial defects, and dental agenesis. OBJECTIVE: Mutations in FGFR1 typically demonstrate reduced penetrance, variable expressivity, and until recently have been exclusively identified in families with anosmia. The purpose of this study was to determine whether FGFR1 mutations were present in a unique family with autosomal dominant, fully penetrant, normosmic IHH. DESIGN: The study is a review of detailed clinical findings, dynamic endocrine studies, and performance of a molecular analysis of the FGFR1 gene. SETTING: The study was carried out in an academic medical center. PATIENTS: All four affected individuals have complete IHH with full penetrance but no anosmia/hyposmia, and they have none of the FGFR1-associated anomalies. In addition, no other family member has anosmia. Inverventions: Interventions included detailed phenotype characterization including history, physical exam, smell testing, dynamic pituitary testing, brain imaging, and molecular analysis. MAIN OUTCOME MEASURES: Outcome was measured by the determination of the severity of IHH, olfactory function, and sequence of the FGFR1 gene. RESULTS: The same heterozygous nonsense mutation, Arg622X, was present in all four affected members, but not in three unaffected members or 100 controls. The mutation is predicted to encode a truncated protein or result in nonsense-mediated decay. CONCLUSIONS: Our findings indicate that mutations in the FGFR1 gene can cause normosmic, fully penetrant, complete IHH with little or no variable expressivity, and without the other FGFR1-associated anomalies typically found in KS.

Adolescent↗
PubMed2006

Genes invoked in the ovarian transition to menopause.

Menopause and the associated declines in ovarian function are major health issues for women. Despite the widespread health impact of this process, the molecular mechanisms underlying the aging-specific decline in ovarian function are almost completely unknown. To provide the first gene-protein analysis of the ovarian transition to menopause, we have established and contrasted RNA gene expression profiles and protein localization and content patterns in healthy young and perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and protein levels that are noted prior to molecular evidence of steroidogenic failure. In this model, ovarian reproductive aging displays similarities with chronic inflammation and increased sensitivity to environmental cues. Overall, our results indicate the presence of mouse climacteric genes that are likely to be major players in aging-dependent changes in ovarian function.

Aging↗
PubMed2005

Characterization and mutation analysis of the human formin-2 (FMN2) gene in women with unexplained infertility.

OBJECTIVE: Formin-2 (Fmn2) mutant mice produce oocytes with meiosis I arrest. Our aim was to describe the human FORMIN-2 (FMN2) gene and to identify DNA sequence polymorphisms in patients with unexplained infertility and multiple failed IVF cycles. DESIGN: Institutional review board-approved observational case-control study. SETTING: Infertility center and university hospital. PATIENT(S): Sixty-two fertile controls and seven subjects with unexplained infertility. INTERVENTION(S): BLASTP (www.ncbi.nlm.nih.gov) was used to map the genomic DNA and complementary DNA sequence of FMN2. Genomic DNA was extracted from blood leukocyte samples. The polymerase chain reaction was used to amplify FMN2 gene exons for analysis by denaturing gradient gel electrophoresis. MAIN OUTCOME MEASURE(S): Characterization of the FMN2 gene and identification of fragment melting polymorphisms (FMPs). RESULT(S): FMN2 includes 411,960 base pairs (bp) of DNA with 6,204 bp in 18 exons. There was no difference in FMN2 FMP allele frequencies between the controls and subjects. One patient was homozygous for one FMP. CONCLUSION(S): The human FMN2 gene is conserved between evolutionarily diverse vertebrates. It is likely that FMN2 has the same function as Fmn2 in the mouse (i.e., maintenance of the meiotic spindle). Prospective identification of patients with meiosis I arrest is necessary to determine whether FMN2 mutations are a cause of unexplained infertility.

Adult↗
PubMed2005

One last chance for pregnancy: a review of 2,705 in vitro fertilization cycles initiated in women age 40 years and above.

OBJECTIVE: To describe live birth rates and predictors of success in 1-year age increments for women > or =40 years when initiating assisted reproductive technologies (ART). DESIGN: Retrospective database analysis. SETTING: A large university-affiliated infertility center. PATIENT(S): One thousand two hundred sixty-three women undergoing 2,705 ART cycles at age 40 or above. INTERVENTION(S): Couples undergoing ART. MAIN OUTCOME MEASURE(S): Pregnancy and live birth rates per cycle start were determined based on 1-year increments in women aged > or =40. Predictors of success, including number of embryos transferred, number of fetal heartbeats, availability of embryos for cryopreservation, and cycle day 3 FSH levels, were analyzed. RESULT(S): The overall live birth rate per cycle start was 9.7%. Cumulative live birth rates in women ranged from 28.4% if starting ART at age 40 to 0 by age 46. The overall spontaneous abortion rate was 32.6% (range, 23.9%-66.7%). Higher pregnancy rates were predicted by the greater number of embryos available for transfer, by the availability of excess embryos for cryopreservation, and by the presence of two fetal heartbeats on ultrasound. The outcome of the first IVF cycle did not predict the outcome of subsequent cycles. CONCLUSION(S): Assisted reproductive technology has a reasonable chance for success (>5%) up until the end of the forty-third year. Twins on initial ultrasound, large numbers of embryos available for transfer, and the presence of excess embryos for cryopreservation predict higher live birth rates.

Adult↗
PubMed2005

Assisted reproductive technology has been detrimental to academic reproductive endocrinology and infertility: depth of the problem and possible solutions.

Dr. Soules' editorial points out some, but not all, of the detrimental effects of assisted reproductive technology on the subspecialty of academic reproductive endocrinology and infertility. This response adds to the list of problems (i.e., discussing the loss of pure endocrinology) but points out an example of a creative solution (i.e., merging academic units with private practices).

Decision Making, Organizational↗
PubMed2004

Variations in individual physician success rates within an in vitro fertilization program might be due to patient demographics.

OBJECTIVE: To determine whether there are variations in individual physician success rates in an IVF program, even with uniform laboratory and treatment protocols. DESIGN: Retrospective analysis. SETTING: Boston IVF, a private practice. PATIENT(S): Patients <38 and 38-40 years of age who underwent non-donor egg, fresh embryo transfer (ET). INTERVENTION(S): Retrospective analysis of IVF success rates for Boston IVF for the year 1999, as reported to the Society of Assisted Reproductive Technology. MAIN OUTCOME MEASURE(S): Each individual physician's clinical pregnancy and live birth rates for patients aged <38 and 38-40 years for the year 1999. Pregnancy rates were also obtained for an "ideal patient group." RESULT(S): Among 13 physicians, the clinical pregnancy rate in the <38-year age group ranged from 20.5% to 35.1% and the live birth rates from 17.8% to 31.1%. For the 38-40-year age group, the clinical pregnancy rate ranged from 10.6% to 29.8% and live birth rates from 7.0% to 25.5%. There was no statistical difference in the clinical pregnancy rate for the ideal patient group. CONCLUSION(S): In the ideal patient group, in which patient demographics are uniform, there are no statistical differences in individual physician performance within the same IVF program. Variation exists in the success rates between the physicians in the <38- and 38-40-year age groups. Possibly this is owing to patient demographics.

Adult↗
PubMed2003

Analysis of cystic fibrosis transmembrane conductance regulator gene mutations in patients with congenital absence of the uterus and vagina.

The relationship between cystic fibrosis transmembrane conductance regulator gene (CFTR) mutations and congenital absence of the uterus and vagina (CAUV) was examined. CFTR mutations have previously been associated with congenital bilateral absence of the vas deferens (CBAVD). CBAVD is caused by a disruption in the vas deferens, a Wolffian duct derivative. Because the embryologic development of the Müllerian ducts directly depends on the prior normal development of the Wolffian ducts, the same gene products may be necessary for normal embryologic development of both ductal systems. This study evaluated the role of CFTR mutations in the development of CAUV. DNA samples from 25 patients with CAUV were tested for the presence of 33 of the most common CFTR mutations. Protein-coding DNA fragments from the CFTR gene were amplified in vitro by the polymerase chain reaction (PCR) and analyzed for mutations using allele-specific oligonucleotide (ASO) probes. Two patients were heterozygous for CFTR mutations. One was heterozygous for the W1282X mutation and the other was heterozygous for the DeltaF508 mutation. The incidence of the 33 CFTR mutations found in the patients with CAUV (8%) was twice that found in the general population (4%), but much less than the incidence of CFTR mutations in men with CBAVD (80%). This data suggests that it is unlikely for CFTR mutations to cause CAUV in females as they cause CBAVD in some males. Furthermore, the data suggest that CAUV in females may be the same disorder as CBAVD in males who do not have CFTR mutations.

Alleles↗
PubMed2003

Subcutaneous versus intramuscular administration of human chorionic gonadotropin during an in vitro fertilization cycle.

OBJECTIVE: To confirm that hCG levels in follicular fluid and serum would be comparable between i.m. and s.c. administration of purified hCG. DESIGN: In a prospective study, serum and follicular fluid levels of hCG after an i.m. or s.c. injection of 10,000 IU of hCG were evaluated 36 hours after injection, that is, at the time of oocyte retrieval. SETTING: This study was carried out in a university-affiliated IVF program. PATIENT(S): Forty women undergoing oocyte retrieval were entered into the study at the time of egg retrieval, that is, 36 hours after hCG administration. INTERVENTION(S): S.c. or i.m. injection of hCG. MAIN OUTCOME MEASURE(S): Serum and follicular fluid concentrations of hCG were evaluated 36 hours after injection at the time of oocyte retrieval. RESULT(S): There was a significantly higher serum hCG level in the s.c. group (348.6 +/- 98 IU/L) vs. the i.m. group (259.0 +/- 115 IU/L) and a significantly higher follicular fluid hCG level in the s.c. vs. the i.m. group (233.5 +/- 85 vs. 143.4 +/- 134 IU/L). CONCLUSION(S): After purified hCG administration via the s.c. route, both serum and follicular fluid levels are greater compared with the i.m. route.

Adult↗
PubMed2003

Normal onset of puberty have definitions of onset changed?

Puberty is the sequence of events that culminates in the ability to procreate. It is widely accepted that the onset of puberty in girls occurs on average at 8 years of age and that onset prior to 8 years of age is precocious puberty. As a result of the cross-sectional study by the American Association of Pediatrics, a movement exists to change the age limit of the onset of puberty to 6 years of age in black girls and 7 years of age in white girls. We should be cautious in adhering to strict age limits when diagnosing precocious puberty. Also the rapidity and progression of puberty should be evaluated, and if appropriate, therapy to suppress pubertal development considered.

Adolescent↗
PubMed2003

Turner syndrome in adolescence.

The management of a patient with Turner syndrome is complex and multi-faceted. It is best accomplished by an interdisciplinary approach. Initial diagnosis is generally prenatal or suggested by physical characteristics. Diagnosis should include karyotype analysis and potentially a probe for Y-chromosome centromeric material to assess the risk for the development of germ cell tumors. At the time of initial diagnosis, the patient should be thoroughly investigated for associated medical conditions. Ongoing surveillance for the development of complications is of paramount importance. The interdisciplinary team should include an endocrinologist; cardiologist; nephrologist; reproductive endocrinologist; audiological physician; ear, nose and throat surgeon; plastic surgeon; dentist; and psychologist . It is important to provide to girls and women with Turner syndrome, and their families, comprehensive information about the syndrome and to advise them about the availability of Turner syndrome societies that can provide information and support.

Adolescent↗
PubMed2003

Contemporary issues in primary amenorrhea.

Reproductive medicine has changed dramatically since the 1981 publication of the study of patients presenting with pubertal amenorrhea. The breakdown of causes likely remains unchanged, with the four most common causes of primary amenorrhea being ovarian failure (48.5%), congenital absence of the uterus and vagina (16.2%), GnRH deficiency (8.3%), and constitutional delay of puberty (6.0%). In the study of patients reported by Reindollar, 60% of patients had barriers to reproduction. Since its publication over 15 years ago, developments in assisted reproductive technologies have enabled pregnancy in many of these patients. Women with ovarian failure may gestate pregnancies from donated oocytes. Women with congenital absence of the uterus and vagina may have their fetuses carried in a surrogate uterus. During this period, the advances of molecular medicine have provided a better understanding of the etiologies of many of these disorders, including Turner's syndrome; 46,XY gonadal dysgenesis; 46,XX gonadal dysgenesis; hypogonadotropic hypogonadism; enzyme-deficient states; gonadotropin resistance; and androgen insensitivity. Contemporary issues related to these disorders involve information about molecular defects and outcome of pregnancies for patients previously considered sterile. Largely, this information has been extremely helpful and reassuring. However, the reported deaths of patients with Turner's syndrome who become pregnant by donor oocyte should remind us to proceed cautiously as new reproductive avenues are opened for these patients.

Adolescent↗