Regulation of Bushen Zhuyun Prescription on Ovarian Endoplasmic Reticulum Stress in Rats with Luteal Phase Defect / 中国实验方剂学杂志

Objective:To investigate the regulatory mechanism of Bushen Zhuyun prescription（BSZYP） on endoplasmic reticulum stress （ERS） in rats with luteal phase defect （LPD） induced by mifepristone. Method:Fifty SD rats were randomly divided into a blank group， a model group， a positive control group （dydrogesterone，0.02 g·kg^-1）， and low-（0.08 g·kg^-1）and high-dose （0.24 g·kg^-1） BSZYP groups. Western blot and Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） were used to detect the mRNA and protein expression levels of immunoglobulin binding protein （BIP）， protein kinase R-like endoplasmic reticulum kinase （PERK）， inositol-requiring enzyme 1 （IRE-1）， activating transcription factor 6 （ATF6）， and C/EBP homologous protein （CHOP）. The enzyme-linked immunosorbent assay （ELISA） was used to detect the serum progesterone （P） and estradiol （E₂） levels. Result:Compared with the blank group， the model group showed the elevated protein expression of BIP， PERK， and CHOP （<italic>P</italic><0.01） and the dwindled mRNA expression of PERK and CHOP （<italic>P</italic><0.05）， while no significant difference was observed in the protein expression of IRE-1 and ATF6， mRNA expression of IRE-1， BIP， and ATF6， and serum E₂ and P levels. Compared with the model group， the positive control group displayed diminished protein expression of CHOP （<italic>P</italic><0.01）， while no significant difference was observed in the protein expression of PERK， IRE-1， BIP， and ATF6， mRNA expression of PERK， IRE-1， BIP， ATF6， and CHOP， and serum levels of E₂ and P. The protein expression of CHOP decreased （<italic>P</italic><0.01） and the mRNA expression of CHOP increased （<italic>P</italic><0.05） in the low-dose BSZYP group， while no significant difference was observed in the mRNA and protein expression of PERK， IRE-1， BIP， and ATF6， and serum E₂ and P levels. In the high-dose BSZYP group， the protein expression of PERK， BIP， and CHOP was down-regulated （<italic>P</italic><0.01）， and the mRNA expression of CHOP was up-regulated （<italic>P</italic><0.01）， while no significant difference was observed in the protein expression of IRE-1 and ATF6， mRNA expression of PERK， IRE-1， BIP， and ATF6， and serum E₂ and P levels. Conclusion:BSZYP can treat LPD by relieving ERS.

Comparative evaluation of tubal patency by hysterosalpingography and laparoscopic chromopertubation

Background: Infertility is defined as one year of unprotected intercourse without pregnancy, primary in which no previous pregnancies have occurred and secondary in which a prior pregnancy not necessarily a live birth has occurred. The objective of the study was to compare the relative efficacy of hysterosalpingography (HSG) and laparoscopy with chromopertubation in the diagnosis of tubal factors in infertile women.Methods: 90 infertile women attending the infertility clinic at Dharmapuri Medical College and Hospital were selected for this study. The study period was from April 2016 to July 2017 these patients were initially counseled along with their partners and a thorough history of both the partners was obtained followed by a general and pelvic examination of female partners.Results: HSG results indicated that 48 patients had tubal pathology and 11 patients had uterine pathology. Of those 11 patients with uterine pathology, 6 patients with synechiae had both tubal and uterine pathology. The remaining 5 had only uterine pathology and tubes were patent in them. The site of tubal occlusion in all those blocked tubes shows that more number of the tubal blockage was seen in mid segment of the tube (24 cases) followed by the fimbrial block in 16 cases. Diagnostic laparoscopy with chromopertubation was performed in all 90 patients and the findings were recorded.Conclusions: HSG has reasonably good sensitivity and specificity in diagnosing tubal pathology of infertile women. But given the high rate of false-positive diagnosis of tubal pathology (29%) in HSG, a follow-up laparoscopy is warranted.

Effect on follicular development and pregnancy outcome treated with acupuncture and moxibustion therapy of in patients with luteal phase defect / 中国针灸

OBJECTIVE@#To observe the effect of acupuncture and moxibustion therapy of on ovulation and embryo implantation in luteal phase defect patients with spleen-kidney deficiency.@*METHODS@#A total of 80 patients were randomly divided into an observation group and a control group, 40 cases in each one.In the observation group,acupuncture was applied at Shenting (GV 24), Shenque (CV 8), Guanyuan (CV 4), Qixue (KI 13), Lieque (LU 7), Gongsun (SP 4), Taixi (KI 3), Zusanli (ST 36) and Taichong (LR 3). And moxibustion was given at Taixi (KI 3) using moxibustion box during follicular phase, the stimulation of Taichong (LR 3) was strengthened during ovulatory phase, moxibustion was adopted at Shenque (CV 8) to Guanyuan (CV 4), Zusanli (ST 36) and Taixi (KI 3) during luteal phase. In the control group, acupuncture was applied at Guanyuan (CV 4), Dahe (KI 12), Sanyinjiao (SP 6), Ciliao (BL 32), Zhibian (BL 54) and Shenque (CV 8). Moxibustion was given at Sanyinjiao (SP 6) using moxibustion box during follicular phase, and moxibustion was adopted at Shenque (CV 8) to Guanyuan (CV 4) during luteal phase. The treatment were given every Monday, Wednesday and Friday, and the treatment were stoped during menstrual period in the two groups. Totally 3 menstrual cycle treatment were required, and 3 menstrual cycles were followed up. The pregnancy rate was observed after treatment, the ovulation rate, maximum folliclular diameter and difference of maximum folliclular diameters in ovulatory phase, serum progesterone (P) and basal body temperature (BBT) were compared before and after treatment in the two groups.@*RESULTS@#In the observation group, 6 cases of successful pregnancy during treatment,10 cases in follow-up, the clinical pregnancy rate was 40.0% (16/40). In the control group, 1 case of successful pregnancy during treatment, 5 cases in follow-up, the clinical pregnancy rate was 15.0% (6/40). The clinical pregnancy rate in the observation group was higher than the control group (0.05). Compared before treatment, the maximum folliclular diameter and difference of maximum folliclular diameters in ovulatory phase, serum P after treatment were improved in the two groups (<0.05), and the improvements of the observation group were significant compared with the control group (<0.05). The BBT after treatment were superior to before treatment in the two groups (<0.05). After treatment, the normal BBT in the observation group was 33 cases, while the control group was 22 cases (<0.05).@*CONCLUSION@#Acupuncture and moxibustion therapy of can promote folliclar development, improve dominant follicle morphology, increase the level of serum P. The therapeutic effect is superior to routine acupuncture in increasing ovulation rate and improving pregnancy outcome.

B ushen Zhuyun Reic pe improves them orphology of the gonad axis of rats with mfi epristone-induced luteal phase defect / 医学研究生学报

Objective The purpose of this study was to construct a rat model of luteal phase defect ( LPD) with mifepristone ( RU486 ) and investigate the improving effect of Bushen Zhuyun Recipe ( BZR ) on the gonad axis morphology of the LPD rat . Meth ods We established rat models of LPD by giving RU486 at 1 mL/100 g followed by treatment with BZR at 0.4 (medium dose) or 1.2 mL/100g ( high dose ) .Then we observed the changes of morphology of the hypothalamus pituitary ovary uterus . Results Electron microscopy revealed hypothalamic mitochondria vacuolization , degranulation of rough endoplasmic reticulum , dissolved nuclear membrane , and decreased secretory granules , while light microscopy exhibited slightly reduced density of pituitary cells , karyopyknosis of some of the cells ,and cytoplasmic vacuolization in the model rats .Electron microscopy also showed obvious shrinkage of cell nuclei , chromatin condensation , disordered cell arrangement , swelling mitochondrial cavity , and formation of vacuoles in the pituitary anterior lobe, while light microscopy also manifested increased ovarian follicular atresia , reduced granule cell layers and corpora lutea , thinned endometrial layers , decreased uterine glands of the tube wall , reduced glandular cavity , and increased interstitial collagen fibers .After BZR treatment, the number and volume of corpora lutea were increased , the granulosa cell layer and endometrial layer thickened , the number of uterine glands increased , and the gland cavity expanded . Conclusion The axes of the hypothalamus , pituitary, uterus,and o -varian were morphologically changed in the RU 486-induced rat models of LPD, while BZR could improve these changes .

Morphological patterns of endometrium in infertile woman-a prospective study.

Background and Objective: Infertility is a global health problem because 8-12% of all couples worldwide, around 80 million are infertile. Endometrium is the most sensitive indicator of ovarian function. Endometrial biopsy with routine hematoxylin and eosin staining is an important investigation in the Indian Scenario. Therefore the present study has undertaken to investigate the morphological patterns of endometrium in infertile women. Materials and Methods: This study was carried out in the Department of Pathology, Bangalore Medical College after the ethical clearance from the institutional ethics committee. The study included 90 cases with complaints of infertility (primary / secondary). The premenstrual D & C was done to obtain endometrial biopsy. The endometrial tissue was fixed; processed, sectioned and performed Hematoxylin & Eosin stain for morphology of endometrium, dating of endometrium and Ziehl-Neelsen (ZN) stain for acid fast bacilli was also performed. In this descriptive analysis, values are mentioned as percentages. Result: In the present study, we also observed 2 cases of Tuberculosis (TB), 5 cases exhibited cystic hyperplasia and only a single case of endometrial polyp was seen. But, the percentage of cases of secretory phase was more. Simple cystic hyperplasia was seen in 3 cases of primary and 2 cases of secondary infertility. Conclusion: In the present study we concluded that the anovulatory endometrium, simple cystic hyperplasia and luteal phase defect formed the major etiological basis of many cases of infertility and the tuberculosis endometritis and endometrial polyp formed the minor group of etiology.

Retrospective Analysis of Zhu Yun Pill in Treating 133 Cases of Infertility due to LPD / 中华中医药杂志

Objective: To investigate the effects of Zhu Yun Pill(ZYP) in the treatment of infertility due to luteal phase defect(LPD).Methods: 163 infertility patients due to LPD were randomly divided into three groups in terms of ZYP group,progesterone group and combination group(ZYP and progesterone).Then the therapeutic efficacy was judged by the pregnancy rate(PR),endometrial biopsy,the level of serum hormone and basal body temperature before and after the treatment.Result: 40 women were pregnant in ZYP group(cure rate,33.33%),8 in the progesterone group(cure rate,26.67%) and 9 in the combination group(cure rate, 69.23%).The symptomatic amelioration and total effective rate of ZYP group were obviously higher than single exogenous progesterone group(P

Expression of Leukemia Inhibitory Factor (LIF) in the Clomiphene Citrate Treated Infertile Women with Luteal Phase Defect / 대한산부인과학회잡지

OBJECTIVE: Although the regulation of implantation is not clearly understood, recent studies have revealed that many cytokines and growth factors play an essential role in preimplantation endometrial development. Among the cytokines, the expression of leukemia inhibitory factor (LIF) is absolutely essential for implantation, although its precise role is not fully understood. Clomiphene citrate is most commonly used drug in the treatment of infertility, but pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to the antiestrogenic effect of it on the cervical mucus and endometrium. The our purpose was to evaluate the endometrial expression of LIF in clomiphene citrate treated infertile women with luteal phase defect and association of clomiphene citrate and unsatisfactory endometrial development. METHODS: The endometrial samples from women with luteal phase defect (n=27) were examined. The endometrial tissue was obtained during secretory phase in 5 cases, and during proliferative phase in 6 cases without clomiphene citrate treatment. In 16 cases, the endometrial tissue was obtained by biopsy during secretory phase after clomiphene citrate treatment. Immunohistochemical staining was performed for LIF in the endometrial tissues. And then the expression of LIF was compared between clomiphene citrate treatment group and no treatment group during secretory phase, and secretory and proliferative phase were compared in the no treatment group. RESULTS: The endometrial expression of LIF was not significantly different between clomiphene citrate treated group and no treated group (p. value=0.123) and between proliferative phase and secretory phase without clomiphene citrate (p. value=0.306). The expressions of LIF were detected mostly in glandular epithelial cells and not in the stromal cells. CONCLUSION: We demonstrated that LIF was expressed in glandular epithelial cells rather than stromal cells and there was not menstrual cycle dependent difference of endometrial expression of LIF in infertile women with luteal phase defect. And our finding suggested that clomiphene citrate did not affect the secretory phase endometrial expression of LIF in infertile women with luteal phase defect.

Comparison of Expression of Endometrial Prolactin in infertile Women with Luteal Phase Defect According to Clomiphene Citrate Administration / 대한불임학회지

OBJECTIVE Clomiphene citrate is one of the most commonly used drugs in the treatment of infertility, but the pregnancy rate achieved with clomiphene citrate is significantly lower than the ovulation rate due to its antiestrogenic effect on the endometrium. Endometrial prolactin is considered to be a marker and an inducer of predecidualization that is characteristic of secretory endometrium. The purpose of this study was to evaluate the association of clomiphene citrate and unsatisfactory endometrial differentiation to secretory endometrium by examining the endometrial expression of prolactin in clomiphene citrate-treated infertile women with luteal phase defect. METHODS: The endometrial samples from infertIle women wIth luteal phase defect (n=27) were examined. Five cases during secretory phase and six cases during proliferative phase were obtained by biopsy. Sixteen cases were obtained by biopsy during secretory phase after clomiphene citrate treatment. By immunohistochemical staining for prolactin, all obtained endometrial tissues were examined. The differences in the endometrial expression of prolactin were evaluated between proliferative phase and secretory phase, and between clomiphene citrate treated group and no treatment group during secretory phase. RESULTS: The staining of endometrial prolactin was significantly more intense in the glandular epithelial cells and stromal cells in the secretory endometrium than in the proliferative endometrium. The glandular expression of prolactin in the secretory endometrium was not significantly different between the clomiphene citrate-treated group and no treatment group (p=0.719), but the staining of prolactin in the stromal cells was significantly less intense in the clomiphene citrate-treated group than no treatment group (p=0.019). CONCLUSION: in this investigation, we demonstrated that the endometrial stromal expression of prolactin in the secretory phase was significantly lower in the clomiphene citrate-treated group campared with no treatment group in infertile women with luteal phase defect. And our finding suggests that clomiphene citrate may have an adverse effect on the endometrial predecidualization in infertile women.

Analysis of Histological Findings and Estrogen and Progesterone Receptor Status in Luteal Phase Defect Caused by Delayed Ovulation and Clomiphen Treatment

Luteal phase defect (LPD) is an ovulatory disorder of considerable clinical importance that leads to delayed endometrial maturation and inadequate endometrium for blastocyst implantation. This disorder is implicated in infertility and recurrent spontaneous abortion. We analyzed the endometrial histological maturation, and the estrogen receptor(ER) and progesterone receptor(PR) status in patients with unexplained delayed ovulation, and in patients with ovulation induction by clomiphen citrate. The purpose of this study was to determine whether the length of the follicular phase influences the endometrial histological maturation and the hormonal receptor status, and to know the effect of clomiphen citrate on the endometrium. In the delayed ovulation group, the endometrium was characterized by an irregular outpouching and dilated lumina of the glands, a decreased secretory activity and predecidualization, and a decreased number of granulocytes in the stroma. In the clomiphen citrate-ovulation induction group, glandular proliferation was markedly diminished with poorly convoluted and narrow glands, secretory activity was decreased, stroma was undecidualized, and there was an absence of granulocytes. ER expression was increased in the glandular epithelium in the delayed ovulation group, and both ER and PR expressions were markedly decreased in the glandular epithelium and stromal cells in the ovulation induction group. Endometrial maturation and differentiation may be diminished by increased estrogenic and relatively deficient progesterone effects in patients with delayed ovulation. The hormonal receptor status might also be influenced by hormonal changes. Clomiphen citrate successfully induced ovulation in patients with delayed ovulation, however, endometrial proliferation and maturation were markedly suppressed. This might be related to the lower pregnancy rate and higher abortion rate in patients with clomiphen citrate induced ovulation.