The effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation(COH) implantation dysfunction were studied. The COH implantation dysfunction model in ...The effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation(COH) implantation dysfunction were studied. The COH implantation dysfunction model in mice was established by intraperitoneal injection of 7.5 IU pregnant mare’s serum gonadotrophin(PMSG), followed by 7.5 IU human chorionic gonadotrophin(HCG) 48 h later. Then the female mice were mated with male at a ratio of 2:1 in the same cage at 6:00 p.m. The female mice from normal group were injected intraperitoneally with normal saline and mated at the corresponding time. Day 1 of pregnancy was recorded by examining its vaginal smears at 8:00 a.m. of the next day. Fifty successfully pregnant mice were equally randomly divided into 5 groups: normal control pregnant group(NC), COH implantation dysfunction model group(COH), low dosage of Bu-Shen-An-Tai recipe group(LOW), middle dosage of Bu-Shen-An-Tai recipe group(MID) and high dosage of Bu-Shen-An-Tai recipe group(HIGH). Then from day 1, the mice in different groups were respectively intragastrically given corresponding treatments at 9:00 a.m. for 5 consecutive days. The concentrations of 17β-estradiol(E) and progesterone(P) were determined by radioimmunoassay(RIA). The ultrastructural changes of ovarian tissues were observed by transmission electron microscope(TEM). The histopathological changes of ovarian tissues were observed by HE staining. The number of atretic follicles and pregnant corpus luteum were also recorded. TUNEL was applied to measure apoptotic cells of ovarian tissues. Western blotting was used to detect the protein expression of apoptosis-related factors like Bax, Bcl-2 and cleaved-caspase-3 in ovarian tissue of mice. The results showed that ovarian weight, the concentrations of Eand P, the number of atretic follicles and pregnant corpus luteum, as well as the apoptosis of granulosa cells were significantly increased in the COH group. The ultrastructures of ovarian tissues in the COH group showed that chromatin in granulosa cells was increased, agglutinated, aggregated or crescent-shaped. The focal cavitation and the typical apoptotic bodies could be seen in granulosa cells in the late stage of apoptosis. After the treatment with different doses of Bu-Shen-An-Tai recipe, the ultrastructural changes of ovarian granulosa cells apoptosis were dramatically improved and even disappeared under TEM. Visible mitochondria and mitochondrial cristae were increased and vacuoles were significantly reduced. The lipid dropltes were shown in a circluar or oval shape. The protein expression levels of Bax and cleaved-caspase-3 were decreased, and the expression of Bcl-2 protein was increased after treatment. It was concluded that Bu-Shen-An-Tai recipe can inhibit the apoptosis of ovarian granulosa cells, probably by up-regulating the protein expression of Bcl-2 and down-regulating Bax and cleaved-caspase-3, which contributes to the formation and maintenance of ovarian corpus luteum. It’s helpful to promote the embryonic implantation, to reduce embryo loss and ultimately to improve the success rate of pregnancy.展开更多
Objective To investigate effects of ovarian high response on endometrial mucin-1 （MUC1） and pinopode in peri-implantation phase in controlled ovarian hyperstimulation （COH） cycles. Methods Ovarian high response wa...Objective To investigate effects of ovarian high response on endometrial mucin-1 （MUC1） and pinopode in peri-implantation phase in controlled ovarian hyperstimulation （COH） cycles. Methods Ovarian high response was defined as serum E2 〉 15 000 pmol/L on the day of hCG administration in COH cycle using GnRH agonist and recombinant FSH （n=8）. Healthy and fertile women were used as the natural control （n=10）. Endometrial biopsies were performed on the day of LH＋ 7/hCG＋ 7. Pinopode formation was observed by scanning electron microscope. Expression of MUC1 was detected with quantitative Real-time PCR and immunohistochemistry. Results In high response group, the lumen surface was covered with variant pinopodes and microvillous. The expression of MUC1 mRNA in high response group was lower than that in the natural control （P〈0.05）. Immunostaining for MUC1 protein in glandular and luminal epithelium in high response group was lower than that in the natural control （P〈0. 05）. Conclusion Asynchronized pinopode appearance and lower expression of MUC1 during peri-implantation period were the characteristics of endometrium in high response group, Which may provide a clue of decreased endometrial receptivity in the supraphysiological hormone milieu.展开更多
This paper is a case report on the success of oocyte retrieval and good quality embryo development following controlled ovarian hyperstimulation at early pregnancy. A 30-year-old patient underwent controlled ovarian h...This paper is a case report on the success of oocyte retrieval and good quality embryo development following controlled ovarian hyperstimulation at early pregnancy. A 30-year-old patient underwent controlled ovarian hyperstimulation by gonadotropin-releasing hormone agonist long protocol. On the day of oocyte collection, a 5-week gestational sac was observed by exact sonography monitoring. However, via ultrasound guided follicle puncture, 7 oocytes were collected. After intarcytoplasmic sperm injection, 3 developed good quality embryos were cryopreserved. Moreover, the natural pregnancy was continued and finally a healthy live birth was achieved. Despite physiological hormonal changes during pregnancy, the follicular growth occurred and followed by oocyte retrieval and embryo development, subsequently.展开更多
The aim of the current study is to analyze the cost of controlled ovarian hyperstimulation (COH) of in vitro fertilization (IVF) during the period 2009-2013 in a specialized gynecology clinic. It is a prospective, obs...The aim of the current study is to analyze the cost of controlled ovarian hyperstimulation (COH) of in vitro fertilization (IVF) during the period 2009-2013 in a specialized gynecology clinic. It is a prospective, observational study and bottom up cost analysis of the COH pharmacotherapy of IVF. The data was collected for all women admitted to the clinic, therapeutic COH protocols, prescribed medicines and doses, average length of therapy and its cost. Statistical analysis is applied towards the pharmacotherapy and cost data. On average 136 (SD 21.92) women were admitted varying from 105 to 179 for 10.7 (SD 1.47) days. 11% were on long (GnRH agonist containing) therapeutic COH protocol and all other on short (GnRH antagonist containing). Therapeutic protocols include Follitropin-α IU (103 women at average dose of 1171 IU (SD 314.16));Follitropin-β IU (299 women at average dose of 1634 IU (SD 423.5));Urofollitropin 75 IU amp (243 women at average dose of 21.3 IU (SD 7.37));urFSH + urLH 75IU:75IU/amp (354 women at average dose of 23.4 IU (SD 8.8));cetrorelix amp 0.25 mg prescribed at 264 women at average dose of 3.84 IU (SD 1.32);ganirelix amp 0.25 mg for 299 women at average dose of 4.01 mg (SD 1.32);Human chorion gonadotropin for 535 women at average dose of 6752.52 IU (SD 1216.23);Nafarelin mcg/ml for 8 women at dose of 17,700 mcg (SD 10,725);triptorelinacetat 0.1 mg amp - 63 women at doses of 5.5 (SD 3.25) mg at 14 women and average dose of 7.5 mg (SD 2.5);clomiphen citrate and letrozole for 15 women at average dose of 8 mg (SD 2.4). The average cost of COH pharmacotherapy is varying among the years with highest value of 1803.776 (SD - 624.89) BGN in 2009. Controlled ovarian hyperstimulation of in vitro fertilization is cost and resource consuming procedure in regards to pharmacotherapy. Age and reason of infertility influence significantly the cost.展开更多
Acupuncture is an important method of treatment in Chinese medicine. The objective of this study was to evaluate the efficacy of acupuncture as an adjuvant treatment for unexplained infertility. Here we conducted a pr...Acupuncture is an important method of treatment in Chinese medicine. The objective of this study was to evaluate the efficacy of acupuncture as an adjuvant treatment for unexplained infertility. Here we conducted a prospective study, with data consisting of acupuncture group (38 cases) and control group (42 cases). Infertility evaluation workup consisted of semen analysis, ovulation assessment, hysterosalpingogram (HSG) and blood analysis. The patients in acupuncture group received 3 acupuncture sessions, and each at seven acupuncture points (EX-CA1, CV4, CV6, SP10, ST36, SP6, and KI3). The session started 12 days before menstruation and continued for 10 days. The patients in control group did not receive acupuncture. All patients tried 1 - 3 natural cycles 3 months after HSG test, if not pregnant, underwent 1 - 3 cycles of control ovarian hyperstimulation (COH) and timed intercourse. Pregnancy was evaluated by measurement of blood β human chorionic gonadotrophin (β-hCG) and subsequent trans-vaginal ultrasound. No significant difference of clinical pregnancy rate was found between the acupuncture group and the control group, however, numbers of COH cycles were significantly less and more pregnancies occurred in natural cycle in the acupuncture group. We concluded that acupuncture can be used as an adjuvant treatment for unexplained infertility. Although acupuncture did not increase the cumulative pregnancy rate, it decreased the number of COH cycles and more patients got pregnant in natural cycles after receiving acupuncture.展开更多
Objective:To investigate the potential relationships among the ovarian response prediction index(ORPI),follicle-oocyte index(FOI),and clinical pregnancy rate(CPR)in women undergoing their first in vitro fertilization/...Objective:To investigate the potential relationships among the ovarian response prediction index(ORPI),follicle-oocyte index(FOI),and clinical pregnancy rate(CPR)in women undergoing their first in vitro fertilization/intracytoplasmic sperm injectionembryo transfer(IVF/ICSI-ET)fresh cycle transfer.Methods:In this retrospective cohort study,we included 12,218 women who underwent their first IVF/ICSI-ET cycle between December 2014 and January 2021.The primary and secondary outcomes of our study were CPR and cumulative live birth rate(CLBR),respectively.The data were divided into three groups according to the ORPI and FOI tertiles.Multivariate logistic regression analyses,stratification analyses,interaction,restricted cubic splines,and receiver operating characteristic(ROC)curves were constructed to identify the relationships among ORPI,FOI,and CPR.Results:A statistically significant increase in CPR was detected from the lowest to the highest tertile group(ORPI:48.12%,54.07%,and 53.47%,P<0.001;FOI:49.99%,52.95%,and 52.71%,P=0.012).A higher CLBR was observed in the high group(ORPI:38.63%,44.62%,and 44.19%,P<0.001;FOI:41.02%,43.78%,and 42.59%,P=0.039).Multivariate logistic regression analysis revealed no statistically significant differences between ORPI,FOI,and neither CPR(odds ratio[OR][95%confidence interval{CI}],0.99[0.97–1.00]vs.[1.02{0.84–1.24}])nor CLBR(OR[95%CI],0.99[0.97–1.01]vs.0.99[0.81–1.20]).No significant association was found among FOI,ORPI,and CPR,even in the subgroups.Restricted cubic spline analyses indicated the existence of a non-linear relationship across the entire range of FOI and ORPI.The ORPI and FOI variables had poor predictive ability(AUC<0.60)for CPR.Conclusions:Both ORPI and FOI are not reliable predictors of clinical pregnancy or live birth outcomes in fresh ETs.Clinicians and researchers should avoid using FOI and ORPI to assess pregnancy outcomes after fresh ET because of their limited relevance and predictive value.展开更多
Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) ...Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.展开更多
基金supported by the National Natural Sciences Foundation of China(No.81473494)
文摘The effect and underlying mechanism of Bu-Shen-An-Tai recipe on ovarian apoptosis in mice with controlled ovarian hyperstimulation(COH) implantation dysfunction were studied. The COH implantation dysfunction model in mice was established by intraperitoneal injection of 7.5 IU pregnant mare’s serum gonadotrophin(PMSG), followed by 7.5 IU human chorionic gonadotrophin(HCG) 48 h later. Then the female mice were mated with male at a ratio of 2:1 in the same cage at 6:00 p.m. The female mice from normal group were injected intraperitoneally with normal saline and mated at the corresponding time. Day 1 of pregnancy was recorded by examining its vaginal smears at 8:00 a.m. of the next day. Fifty successfully pregnant mice were equally randomly divided into 5 groups: normal control pregnant group(NC), COH implantation dysfunction model group(COH), low dosage of Bu-Shen-An-Tai recipe group(LOW), middle dosage of Bu-Shen-An-Tai recipe group(MID) and high dosage of Bu-Shen-An-Tai recipe group(HIGH). Then from day 1, the mice in different groups were respectively intragastrically given corresponding treatments at 9:00 a.m. for 5 consecutive days. The concentrations of 17β-estradiol(E) and progesterone(P) were determined by radioimmunoassay(RIA). The ultrastructural changes of ovarian tissues were observed by transmission electron microscope(TEM). The histopathological changes of ovarian tissues were observed by HE staining. The number of atretic follicles and pregnant corpus luteum were also recorded. TUNEL was applied to measure apoptotic cells of ovarian tissues. Western blotting was used to detect the protein expression of apoptosis-related factors like Bax, Bcl-2 and cleaved-caspase-3 in ovarian tissue of mice. The results showed that ovarian weight, the concentrations of Eand P, the number of atretic follicles and pregnant corpus luteum, as well as the apoptosis of granulosa cells were significantly increased in the COH group. The ultrastructures of ovarian tissues in the COH group showed that chromatin in granulosa cells was increased, agglutinated, aggregated or crescent-shaped. The focal cavitation and the typical apoptotic bodies could be seen in granulosa cells in the late stage of apoptosis. After the treatment with different doses of Bu-Shen-An-Tai recipe, the ultrastructural changes of ovarian granulosa cells apoptosis were dramatically improved and even disappeared under TEM. Visible mitochondria and mitochondrial cristae were increased and vacuoles were significantly reduced. The lipid dropltes were shown in a circluar or oval shape. The protein expression levels of Bax and cleaved-caspase-3 were decreased, and the expression of Bcl-2 protein was increased after treatment. It was concluded that Bu-Shen-An-Tai recipe can inhibit the apoptosis of ovarian granulosa cells, probably by up-regulating the protein expression of Bcl-2 and down-regulating Bax and cleaved-caspase-3, which contributes to the formation and maintenance of ovarian corpus luteum. It’s helpful to promote the embryonic implantation, to reduce embryo loss and ultimately to improve the success rate of pregnancy.
基金This study was supported by grants from the Shanghai Scientific Technology Council (No.034119861)a:Contributed equally to the paper
文摘Objective To investigate effects of ovarian high response on endometrial mucin-1 （MUC1） and pinopode in peri-implantation phase in controlled ovarian hyperstimulation （COH） cycles. Methods Ovarian high response was defined as serum E2 〉 15 000 pmol/L on the day of hCG administration in COH cycle using GnRH agonist and recombinant FSH （n=8）. Healthy and fertile women were used as the natural control （n=10）. Endometrial biopsies were performed on the day of LH＋ 7/hCG＋ 7. Pinopode formation was observed by scanning electron microscope. Expression of MUC1 was detected with quantitative Real-time PCR and immunohistochemistry. Results In high response group, the lumen surface was covered with variant pinopodes and microvillous. The expression of MUC1 mRNA in high response group was lower than that in the natural control （P〈0.05）. Immunostaining for MUC1 protein in glandular and luminal epithelium in high response group was lower than that in the natural control （P〈0. 05）. Conclusion Asynchronized pinopode appearance and lower expression of MUC1 during peri-implantation period were the characteristics of endometrium in high response group, Which may provide a clue of decreased endometrial receptivity in the supraphysiological hormone milieu.
文摘This paper is a case report on the success of oocyte retrieval and good quality embryo development following controlled ovarian hyperstimulation at early pregnancy. A 30-year-old patient underwent controlled ovarian hyperstimulation by gonadotropin-releasing hormone agonist long protocol. On the day of oocyte collection, a 5-week gestational sac was observed by exact sonography monitoring. However, via ultrasound guided follicle puncture, 7 oocytes were collected. After intarcytoplasmic sperm injection, 3 developed good quality embryos were cryopreserved. Moreover, the natural pregnancy was continued and finally a healthy live birth was achieved. Despite physiological hormonal changes during pregnancy, the follicular growth occurred and followed by oocyte retrieval and embryo development, subsequently.
文摘The aim of the current study is to analyze the cost of controlled ovarian hyperstimulation (COH) of in vitro fertilization (IVF) during the period 2009-2013 in a specialized gynecology clinic. It is a prospective, observational study and bottom up cost analysis of the COH pharmacotherapy of IVF. The data was collected for all women admitted to the clinic, therapeutic COH protocols, prescribed medicines and doses, average length of therapy and its cost. Statistical analysis is applied towards the pharmacotherapy and cost data. On average 136 (SD 21.92) women were admitted varying from 105 to 179 for 10.7 (SD 1.47) days. 11% were on long (GnRH agonist containing) therapeutic COH protocol and all other on short (GnRH antagonist containing). Therapeutic protocols include Follitropin-α IU (103 women at average dose of 1171 IU (SD 314.16));Follitropin-β IU (299 women at average dose of 1634 IU (SD 423.5));Urofollitropin 75 IU amp (243 women at average dose of 21.3 IU (SD 7.37));urFSH + urLH 75IU:75IU/amp (354 women at average dose of 23.4 IU (SD 8.8));cetrorelix amp 0.25 mg prescribed at 264 women at average dose of 3.84 IU (SD 1.32);ganirelix amp 0.25 mg for 299 women at average dose of 4.01 mg (SD 1.32);Human chorion gonadotropin for 535 women at average dose of 6752.52 IU (SD 1216.23);Nafarelin mcg/ml for 8 women at dose of 17,700 mcg (SD 10,725);triptorelinacetat 0.1 mg amp - 63 women at doses of 5.5 (SD 3.25) mg at 14 women and average dose of 7.5 mg (SD 2.5);clomiphen citrate and letrozole for 15 women at average dose of 8 mg (SD 2.4). The average cost of COH pharmacotherapy is varying among the years with highest value of 1803.776 (SD - 624.89) BGN in 2009. Controlled ovarian hyperstimulation of in vitro fertilization is cost and resource consuming procedure in regards to pharmacotherapy. Age and reason of infertility influence significantly the cost.
文摘Acupuncture is an important method of treatment in Chinese medicine. The objective of this study was to evaluate the efficacy of acupuncture as an adjuvant treatment for unexplained infertility. Here we conducted a prospective study, with data consisting of acupuncture group (38 cases) and control group (42 cases). Infertility evaluation workup consisted of semen analysis, ovulation assessment, hysterosalpingogram (HSG) and blood analysis. The patients in acupuncture group received 3 acupuncture sessions, and each at seven acupuncture points (EX-CA1, CV4, CV6, SP10, ST36, SP6, and KI3). The session started 12 days before menstruation and continued for 10 days. The patients in control group did not receive acupuncture. All patients tried 1 - 3 natural cycles 3 months after HSG test, if not pregnant, underwent 1 - 3 cycles of control ovarian hyperstimulation (COH) and timed intercourse. Pregnancy was evaluated by measurement of blood β human chorionic gonadotrophin (β-hCG) and subsequent trans-vaginal ultrasound. No significant difference of clinical pregnancy rate was found between the acupuncture group and the control group, however, numbers of COH cycles were significantly less and more pregnancies occurred in natural cycle in the acupuncture group. We concluded that acupuncture can be used as an adjuvant treatment for unexplained infertility. Although acupuncture did not increase the cumulative pregnancy rate, it decreased the number of COH cycles and more patients got pregnant in natural cycles after receiving acupuncture.
文摘Objective:To investigate the potential relationships among the ovarian response prediction index(ORPI),follicle-oocyte index(FOI),and clinical pregnancy rate(CPR)in women undergoing their first in vitro fertilization/intracytoplasmic sperm injectionembryo transfer(IVF/ICSI-ET)fresh cycle transfer.Methods:In this retrospective cohort study,we included 12,218 women who underwent their first IVF/ICSI-ET cycle between December 2014 and January 2021.The primary and secondary outcomes of our study were CPR and cumulative live birth rate(CLBR),respectively.The data were divided into three groups according to the ORPI and FOI tertiles.Multivariate logistic regression analyses,stratification analyses,interaction,restricted cubic splines,and receiver operating characteristic(ROC)curves were constructed to identify the relationships among ORPI,FOI,and CPR.Results:A statistically significant increase in CPR was detected from the lowest to the highest tertile group(ORPI:48.12%,54.07%,and 53.47%,P<0.001;FOI:49.99%,52.95%,and 52.71%,P=0.012).A higher CLBR was observed in the high group(ORPI:38.63%,44.62%,and 44.19%,P<0.001;FOI:41.02%,43.78%,and 42.59%,P=0.039).Multivariate logistic regression analysis revealed no statistically significant differences between ORPI,FOI,and neither CPR(odds ratio[OR][95%confidence interval{CI}],0.99[0.97–1.00]vs.[1.02{0.84–1.24}])nor CLBR(OR[95%CI],0.99[0.97–1.01]vs.0.99[0.81–1.20]).No significant association was found among FOI,ORPI,and CPR,even in the subgroups.Restricted cubic spline analyses indicated the existence of a non-linear relationship across the entire range of FOI and ORPI.The ORPI and FOI variables had poor predictive ability(AUC<0.60)for CPR.Conclusions:Both ORPI and FOI are not reliable predictors of clinical pregnancy or live birth outcomes in fresh ETs.Clinicians and researchers should avoid using FOI and ORPI to assess pregnancy outcomes after fresh ET because of their limited relevance and predictive value.
基金This work was supported by the National Natural Science Foundation of China (Nos.81471455,81100418).
文摘Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.
