Clinical Analysis And Relative Genetic Study Of Chinese Infertility Women With Premature Ovarian Failure

Section IClinical analysis of Chinese infertility women with premature ovarian failureOBJECTIVE To investigate the clinical features and types of etiology of infertility women with POF; to analyze the features of the endocrinal sex hormone and to evaluate the value of the treatments to these cohorts' women. METHODS This study retrospectively summarized and analyzed the etiology features, diagnosis and therapy of 138 infertility women with POF. 45 of women also participated in the correlation study of the serum inhibin B (INHB) with other sex hormone by case control. We analyaed the dependablity between INHB with other sex hormone and did the curve fitting between them. RESULTS (1) There were 18 cases (13.04%) with apparent causes of POF. Among them, there were 2 had operation on ovary; 3 had taken medcine with ovarial toxcity or had contaction history with poison; 2 had whole or local immunity disorder and 9 with abnormal karyotype. Besides hypoestrogenemia symptom, there were no apparent severe disease such as cerebrovascular disorder and angiocardiopathy. (2) There were 7 primary amenorrhea and 131 secondary amenorrhea. 110 (79.71%) primary infertility and 28 (20.29%) secondary infertility composed the POF group. There were 4 cases's parents wereconsanguineous marriage and 9 cases with infertility or early menopause history. All patients had symptoms of emotional instability, lassitude and remembrance decreasing etc. in different degree, also accompanied by genitourinary tract atrophy. All the symptoms correlated with duration and curation of the disease. (3) INHB absorbance, concentration, E₂, PRL and testosterone in POF group is lower than in control while FSH and LH is higher in POF than in control (p<0.05). (4) There were no correlation on FSH or LH with INHB in both POF and control group. No correlation with E₂ and INHB in POF (p>0.05), but there exists positive correlation with E₂ and INHB in control. However, negative correlation between INHB with FSH (r=-0.748, p<0.01) and with LH (r=-0.693, p<0.01) and positive correlation with INHB and E₂ (r=0.617, p<0.01). (5) The relation of INHB and FSH is fit linear function, so is INHB with E₂. Inverse function closes the relationship between INHB and LH. (6) Hypoestrogenemia symptoms were well improved after hormone replacement therapy (HRT). FSH was decreased apparently after HRT (p<0.05), though the same with LH and E₂, there's no difference after HRT (p<0.05). (7) 2 patients got pregnant without ovarian stimulation and 1 woman got pregnant through HMG/HCG ovarian stimulation after HRT. The over all pregnancy rate is 2.17% (3/138). CONCLUSION (1) The infertility women with POF had well development and are fit for HRT and pregnancy. (2) Genetic factor is an important etiology of infertility with POF and genetic screening is necessary in these women. (3) Androgen disorder also included with sex hormone disorder in infertility with POF. INHB can be choosed as one of index of sex hormone disorders in these patients. (4) Estrogen replacement therapy could improve endocrinal condition in infertility with POF. (5) The spontaneous pregnancy rate in infertiligy with POF is low, other ART may do some help. Section IIKaryotype analysis of infertility womenwith PrematureOvarian Failure OBJECTIVE The purpose of this study was to analyze the abnormal karyotype rate ininfertility with POF. To study the abnormal site of chromosome in infertility with POF. METHODS We examined 65 infertility with POF by G-banding technology, then screened and took photos of the karyotypes. RESULT (1) There were 54 (83.08%) cases with normal karyotype (46, XX) and 11 (16.92%) cases with abnormal karyotype. There were 9 abnormal ones concentrated on X chromosome and 1 on autosome, and 1 with balance of chromosome between X and autosome. (2) Here's the details of abnomal karyotype: 4 Turner karyotypes: 45, XO; 2 with mosaicism Turner: 45,XO/46,XX, 45,XO/47,XXX; 1 with mosaicism of isobrachial X phocomelic arm: 45, X/46, X, i (Xp); 1 with mosaicism of X ring chromosome: 45, X/46, X, r (x) (p22-q25); 1 with micro-deletion in X long arm: 46, XX, del (Xq) (25); 1 with chromosome translocation between chromosome 14 and X: 46, XX, t (X;14) (q22,q23) and 1 with chromosome translocation between chromosome 13 and 14: 45, XX, -13, -14, t(13,14). (3) There were 4 cases had breakage, rearragement and deletion in X chromosome. The break points were concentrated on Xq22-Xq25. CONCLUSION (1) It is necessary to exam the karyotype of POF for the high abnormal karyotype rate in the infertility women with POF. (2) Great propotion karyotype abnormal happened on X chromosome. Disorders in the long arm of X chromosome contributed much to ovarian dysfunction. (3) Morden molecular biology is helpful to find minor choromosome disorders. Section IIISequence variants in exons of BMP15 gene in infertility women withPremature Ovarian FailureOBJECTIVE To analyze mutations in the protein region of BMP15 gene in Chinese women with POF. MATERIALS AND METHODS We directly sequenced the exons in BMP15 gene of 92 patients and 76 healthy regularly cycling controls in the study. Clinical features also analyzed between the two groups. RESULTS (1) We didn't find any mutation in BMP15 gene protein coding region. (2) There was no difference incidence of the SNP rs(3810682C->G: ssl6336587) (P>0.05) in the 5'-UTR of exonl in two groups. (3) There was no difference incidence of the SNP rs17003221 (C->T) in exon2 (P>0.05) in two groups (4) The allele genes frequency in the SNP rs(3810682C->G: ss16336587) was C (97.92%) and G (2.083%) respectively in Chinese women, which is different from other races. (5) The same results in FSH, LH, To and E₂. However, there was no difference in PRL in two groups (p>0.05). CONCLUSIONS (1) Our findings indicated that mutations in BMP15 exons in BMP15 propeptide are rare in Chinese women with POF. (2) Our data suggested that the two SNPs are not related to the POF in Chinese women. (3) Our results provide further evidence that SNP variation exists in different races. (4) The changes of PRL in POF is not decided yet. Section IVThe duplicate freqency in 5'-UTR of exonl in FMR1 gene in infertility women with Premature Ovarian FailureOBJECTIVE To the duplicate freqency in 5'-UTR of exonl in FMR1 gene in infertility women with Premature Ovarian Failure. METHODS Polyacrylamide gel electrophoresis were used to analyze in the duplicate freqency in 5'-UTR of exonl in FMR1 gene of 92 patients and 76 healthy regularly cycling controls in the study. Then checked by fluorescent PCR/capillary electrophoresis (CE). RESULTS (1) There was no difference in constituent ratio in quartette of (CGG)n duplicate freqencey: < 18, 18-35, 36-52, > 52 between infertility with POF group and the control (x²=5.3526, p > 0.05) in PAGE glue results. The rate of duplicate frequency of (CGG)n exceeding 36 is higher in infertility with POF than in control (p<0.05). (2) There was significant difference of (CGG)n repeat number in FMR1 gene between patients and controls. The median one is 26. (3) There was no correlation with FMR1 gene premature and POF with infertility in Chinese women. However, the number of CGG repeat was significant higher in patients than in controls (p<0.05). (4) The number of CGG in FMR1 gene had no correlation with amenorrhea age and serum FSH (p>0.05). CONCLUSIONS (1) Fluorescent PCR technology is a convenient, economical and precise method to screen the duplicate freqency in 5'-UTR of exon1 in FMR1 gene. (2) The prematuation of FMR1 gene is not correlated with POF. The number of CGG repeat was significant higher in patients than in controls but in normal range. However, the mechanism and the devided limits of CGG repeat number in different races needs further study. (3) Genetic screening in FMR1 gene is necessary in infertility with POF. And the gene analysis and family survey is also need when necessary.