Clinical Efficacy of Oral Dydrogesterone Alone in Natural Cycle Frozen-thawed Embryo Transfer / 中山大学学报(医学科学版)

ObjectiveTo investigate the clinical efficacy of oral dydrogesterone alone for luteal phase support in natural cycle frozen-thawed embryo transfer （NC-FET）. MethodsThe clinical data of 1 530 NC-FET cycles enrolled in our Reproductive Center from January 2019 to September 2021 were retrospectively analyzed. According to different luteal support protocols， the patients were divided into oral dydrogesterone alone （group A， n=524）， vaginal progesterone soft capsules （group B， n=401） and vaginal progesterone soft capsules combined with dydrogesterone （group C， n=605）. The clinical outcomes and cost-effectiveness ratio were compared among the three groups. The primary outcome was live birth rate. ResultsThe live birth rate was 43.13% （226/524） in group A， 39.15% （157/401） in group B， and 42.64% （258/605） in group C. There was no statistical difference among the three groups （P > 0.05）. No statistical difference was observed in the HCG positive rate， implantation rate， biochemical pregnancy rate， clinical pregnancy rate， spontaneous miscarriage rate， ectopic pregnancy rate， twin delivery rate， premature delivery rate and newborn weight among the three groups （P>0.05）. Logistic regression analysis revealed that the three luteal support regimens did not affect live birth rate. Pharmacoeconomic analysis showed that taking group B as a reference， the cost increased by 19 227.30 yuan for every 1% increase in live birth rate in group A. ConclusionsIn NC-FET cycle， oral dydrogesterone alone can achieve the same clinical outcomes as vaginal progesterone soft capsules and vaginal progesterone soft capsules combined with dydrogesterone. Compared with that of progesterone soft capsules， the cost of oral dydrogesterone alone is increased， a large sample and multicenter prospective study is needed to further confirm our results.

The Addition of Dydrogesterone after Frozen Embryo Transfer in Hormonal Substituted Cycles with Low Progesterone Levels / Uso adicional de didrogesterona após transferência de blastocisto em ciclos substituídos com valores baixos de progesterona

Abstract Objective To determine whether a rescue strategy using dydrogesterone (DYD) could improve the outcomes of frozen embryo transfer cycles (FET) with low progesterone (P4) levels on the day of a blastocyst transfer. Methods Retrospective cohort study including FET cycles performed between July 2019 and October 2020 following an artificial endometrial preparation cycle using estradiol valerate and micronized vaginal P4 (400 mg twice daily). Whenever the serum P4 value was below 10 ng/mL on the morning of the planned transfer, DYD 10 mg three times a day was added as supplementation. The primary endpoint was ongoing pregnancy beyond 10 weeks. The sample was subdivided into two groups according to serum P4 on the day of FET: low (< 10 ng/mL, with DYD supplementation) or normal (above 10 ng/mL). We performed linear or logistic generalized estimating equations (GEE), as appropriate. Results We analyzed 304 FET cycles from 241 couples, 11.8% (n = 36) of which had serum P4 below 10 ng/mL on the FET day. Baseline clinical data of patients was comparable between the study groups. Overall, 191 cycles (62.8%) had a biochemical pregnancy, of which 131 (44,1%) were ongoing pregnancies, with a 29,8% miscarriage rate. We found no statistically significant differences in the hCG positive (63 vs 64%) or ongoing pregnancy rates (50 vs 43,3%) between those FETs with low or normal serum P4 values, even after multivariable logistic regression modelling. Conclusion Our results indicate that DYD 10 mg three times a day administered in women who perform FET with P4 serum levels < 10 ng/mL, allows this group to have pregnancy rates beyond 12 weeks at least as good as those with serum levels above 10 ng/mL.

Resumo Objetivo Determinar se uma estratégia de resgate usando didrogesterona (DYD) pode melhorar os resultados dos ciclos de transferência de embriões congelados (TEC) com baixos níveis de progesterona (P4) no dia de uma transferência de blastocisto. Métodos Estudo de coorte retrospectivo que incluiu ciclos TEC realizados entre julho de 2019 e outubro de 2020 após um ciclo de preparação endometrial artificial usando valerato de estradiol e P4 vaginal micronizado (400 mg duas vezes ao dia). Sempre que o valor de P4 sérico estava abaixo de 10 ng/mL na manhã da transferência planejada, adicionou-se 10 mg de DYD tri-diário como suplementação. O desfecho primário foi gravidez evolutiva após 10 semanas. A amostra foi subdividida em dois grupos de acordo com o P4 sérico no dia da TEC: baixo (< 10 ng/mL, com suplementação de DYD) ou normal (acima de 10 ng/mL). Realizamos equações de estimativa generalizada linear ou logística (GEE), conforme apropriado. Resultados Analisaram-se 304 ciclos de FET de 241 casais, dos quais 11,8% (n = 36) tinham valores de P4 sérico abaixo de 10 ng/mL no dia da TEC. Os dados clínicos e demográficos dos pacientes eram comparáveis entre os grupos. Globalmente, 191 ciclos (62,8%) tiveram uma gravidez bioquímica, dos quais 131 (44,1%) foram gestações em curso, com uma taxa de aborto espontâneo de 29,8%. Não encontramos diferenças estatisticamente significativas na taxa de gravidez bioquímica (63 vs. 64%) ou nas taxas de gravidez evolutiva (50 vs. 43,3%) entre TEC com valores séricos de P4 baixos ou normais, mesmo após modelação com regressão logística multivariável. Conclusão Nossos resultados indicam que a suplementação com DYD 10 mg três vezes ao dia em mulheres com níveis séricos de P4 abaixo de 10 ng/mL em ciclos de TEC substituídos parecem conseguir resultados pelo menos tão bons como nos ciclos com valores superiores para taxas de gravidez em curso além de 12 semanas.

El anillo vaginal de progesterona como soporte de la fase lútea en fertilización in vitro

Objetivo. Comparar la efectividad del anillo vaginal y las cápsulas vaginales de progesterona en el soporte de la fase lútea en procedimientos de fertilización in vitro. Métodos. Estudio retrospectivo que evaluó los resultados de embarazo en mujeres receptoras de embriones logrados de donación de ambos gametos al comparar la efectividad del anillo vaginal y las cápsulas vaginales de progesterona en el soporte de la fase lútea en procedimientos de fertilización in vitro. Resultados. 38 mujeres usaron el anillo vaginal y 46 aplicaron las cápsulas vaginales como soporte de la fase lútea. Se halló tasas similares de implantación (36,5% versus 36,9%), embarazo clínico (52,6% versus 50,0%) y nacido vivo (50,0% versus 45,7%). Conclusiones. Se halló tasas similares de implantación, embarazo clínico y nacido vivo con el empleo del anillo vaginal y las cápsulas vaginales de progesterona en el soporte de la fase lútea en procedimientos de fertilización in vitro. Debido a la comodidad de su uso y a las adecuadas tasas de embarazo, el anillo vaginal de progesterona se constituye como una alternativa importante en el soporte de la fase lútea en la fertilización in vitro.

Objective: To compare the effectiveness of the vaginal ring and vaginal progesterone capsules in supporting the luteal phase in in vitro fertilization procedures. Methods: Retrospective study that evaluated pregnancy outcomes in female recipients of embryos obtained from donation of both gametes by comparing the effectiveness of the vaginal ring and vaginal progesterone capsules in supporting the luteal phase in in vitro fertilization procedures. Results: Thirty-eight women used the vaginal ring and 46 applied vaginal capsules as luteal phase support. Similar rates of implantation (36.5% versus 36.9%), clinical pregnancy (52.6% versus 50.0%) and live birth (50.0% versus 45.7%) were found. Conclusions: Similar implantation, clinical pregnancy and live birth rates were found with the use of the vaginal ring and vaginal progesterone capsules in the support of the luteal phase in in vitro fertilization procedures. Due to the convenience of its use and adequate pregnancy rates, the progesterone vaginal ring is an important alternative in the support of the luteal phase in in vitro fertilization.

Effect of adjuvant growth hormone during luteal phase on in-vitro fertilization-embryo transfer outcome / 中国医师杂志

Objective:To investigate the effect of growth hormone (GH) supplementation during luteal phase one cycle before ovulation induction in patients undergoing in vitro fertilization-embryo transfer (IVF-ET).Methods:IVF-ET pregnancy-assisted patients who underwent long-term Gonadotropin Releasing Hormone-agonist (GnRH-a) protocol from January 1, 2019 to June 30, 2020 were collected from the Reproductive Center of Hunan Provincial Maternal and Child Health Hospital. Among them, 106 patients (GH group) were added with GH during luteal phase one cycle before ovulation induction, and 212 patients (control group) were not added with GH. Ovulation induction and pregnancy outcome were compared between the two groups.Results:(1) There was no statistically significant difference in primary infertility/secondary infertility rate, infertility years, age, and transplant cancellation cycle rate between the two groups (all P>0.05). (2) There were no significant differences in the number of oocytes obtained, MII oocytes, two pronucleus (2PN) oocytes, high-quality embryos and average number of transplanted embryos between GH group and control group (all P>0.05). The total amount of Gn in control group and GH group was (2 109.75±555.75)IU and (1 863±610.52)IU, respectively, with statistically significant difference ( P<0.05). (3) The embryo implantation rate of the control group and GH group was 43.73%(129/295) and 60.42%(87/144), respectively, with statistically significant difference ( P<0.05). The clinical pregnancy rates of the control group and GH group were 58.79%(107/182) and 71.91%(64/89), the difference was statistically significant ( P<0.05). The spontaneous abortion rate of early pregnancy in control group (4.67%, 5/107) was slightly higher than that in GH group (3.12%, 2/64), but there was no significant statistical difference ( P>0.05). Conclusions:For patients with normal ovarian response, adding small dose of growth hormone during luteal stage one cycle before controlled hyperovulation can improve the embryo implantation rate and clinical pregnancy rate, and reduce the amount of Gn, which is beneficial to patients.

Mechanism of Bushen Zhuyun Prescription on Improving Luteal Function of Brown Norway Rats Based on MAPKs Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the possible mechanism of Bushen Zhuyun prescription （BSZYP） to reduce the level of ovarian apoptosis in Brown Norway （BN） rats with luteal phase deficiency （LPD）. MethodFifty SPF female BN rats were randomly divided into a model group， a dydrogesterone group （0.002 g·kg-1）， and a low （4.5 g·kg-1）， a medium （9 g·kg-1）， and a high-dose （18 g·kg-1） BSZYP groups， with ten rats in each group. The rats were administrated with corresponding drugs by gavage， once a day for three estrus cycle. Western blot was used to detected the protein expression levels of c-Jun NH2 terminal kinase （JNK）， extracellular signal-regulated kinase （ERK）， phosphorylated-ERK （p-ERK）， phosphorylated-JNK （p-JNK）， p38 mitogen-activated protein kinase （p38 MAPK）， phosphorylated-p38 MAPK （p-p38 MAPK ）， B-cell lymphoma （Bcl-2）， and Bcl-2 associated X protein （Bax） in ovary. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of ERK， JNK， p38 MAPK， Bax， and Bcl-2 in ovary. Enzyme-linked immunosorbent assay （ELISA） was used to detect the serum progesterone （P） and estradiol （E2） levels. Hematoxylin-eosin （HE） staining was used to observe the ovarian tissue morphology. ResultCompared with the model group， the recovery of estrus cycle of rats in all BSZYP groups had statistical significance after 1-circle administration （P<0.05）. The ovarian tissue morphology in the low-dose BSZYP group was improved， and that in the medium and high-dose BSZYP groups was significantly improved with clear follicle， less vesicular follicle and atretic follicle， and more granular layers. The number of luteum， especially the fresh luteum， in the medium and high-dose groups was increased with smooth edge and large volume. The mRNA expression level of Bcl-2 was increased in all-dose BSZYP groups， while the mRNA expression level of Bax was significantly decreased in all-dose BSZYP group （P<0.05， P<0.01）. The mRNA expression levels of JNK and p38 MAPK were significantly decreased in the high-dose BSZYP group （P<0.01）， and the mRNA expression levels of ERK were increased in the low and medium-dose BSZYP groups （P<0.05）. The protein expression level of Bcl-2 was significantly increased in the medium and high-dose BSZYP groups （P<0.01）， and the protein expression level of Bax was significantly decreased in the all-dose BSZYP groups （P<0.01）. No significant difference was observed in the protein expressions of JNK， ERK， and p38 MAPK in the BSZYP groups. The protein expression levels of p-ERK in the ovarian tissues of rats were significantly inoreased in the medium and high-dose BSZYP group （P<0.01）， p-JNK， and p-p38 MAPK in the ovarian tissues of rats were significantly decreased in the medium and high-dose BSZYP group （P<0.01）. The level of E2 was increased in all-dose BSZYP groups （P<0.05， P<0.01）， and the level of P in the medium-dose BSZYP group was increased （P<0.05）. ConclusionBSZYP improved the serum sex hormones， restored the estrous cycle， reduced atretic follicle and vesiculation， and maintained luteal morphology and function of BN rats， so as to improve luteal function and treat luteal phase deficiency. The mechanism of BSZYP may be related to reduce the level of ovarian tissue apoptosis in BN rats by regulating MAPKs signaling pathway.

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.

Letrozole versus gonadotropin-releasing hormone antagonist during luteal phase in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial / 中华妇产科杂志

Objective@#To explore and compare the preventive effect of using letrozole and gonadotropin-releasing hormone (GnRH) antagonist during luteal phase of patients at high risk for ovarian hyperstimulation syndrome (OHSS).@*Methods@#A total of 99 infertile women undergoing in vitro fertilization and embryo transfer or intracytoplasmic sperm injection with high risk for OHSS were enrolled in this randomized controlled trial.The letrozole group (n=51) received letrozole of 7.5 mg daily for 3 days;the GnRH antagonist group (n=48) were given cetrorelix of 0.25 mg subcutaneously daily for 3 days. Both groups received support therapy combined with embryo cryopreservation. The incidence of OHSS was surveyed. And the serum concentration of estradiol, LH and progesterone on days 3, 5 and 8 after oocytes retrieval were measured.@*Results@#There were no statistical differences in terms of baseline characteristics of patients and outcomes of controlled ovarian hyperstimulation between the two groups.The incidence of moderate and severe OHSS was found no significantly difference between letrozole group [11.8%(6/51)] and GnRH antagonist group [10.4%(5/48);P>0.05]. The estradiol concentration of the indicated days on days 3,5 and 8 after oocytes retrieval in letrozole group and GnRH antagonist group were (1 417±3 543) versus (15 210±9 921) pmol/L, (1 692±4 330) versus (18 680±11 567) pmol/L, (239±336) versus (3 582±5 427) pmol/L, respectively;compared with GnRH antagonist group, the estradiol level was significantly lower in the letrozole group (all P<0.01). The luteinizing hormone level in the letrozole group were (0.46±0.40), (0.56±0.55)and (0.67±0.58) U/L on days 3,5 and 8 after oocytes retrieval, which were significantly higher than those of GnRH antagonist group [(0.28±0.28), (0.30±0.19) and (0.45±0.37) U/L, respectively; all P<0.05]. There was no obvious differences on progesterone levels between letrozole group and GnRH antagonist group (all P>0.05),and on days 8 after oocytes retrieval,the level of progesterone in each group were significantly lower than those on day 3 and 5 after oocytes retrieval (P<0.05).@*Conclusion@#Letrozole has the same efficiency as GnRH antagonist for the prevention of OHSS, faster and cheaper to use, but its efficacy seems not to be related to the suppression of steroidogenic during the luteal phase.

Evaluación de la tasa de blastocistos euploides en fase folicular y lútea (DuoStim) en mujeres con pobre respuesta ovárica: estudio preliminar en México / Euploid blastocyst rate in follicular vs luteal phase (DuoStim) in women with poor ovarian response: Preliminary study in Mexico

Resumen: OBJETIVO: Comparar la tasa de blastocistos euploides obtenida después de la estimulación ovárica en fase folicular con la fase lútea en un mismo ciclo menstrual en pacientes con deficiente respuesta ovárica. MATERIALES Y MÉTODOS: Estudio clínico, prospectivo y comparativo llevado a cabo en el Centro de Reproducción Arcos, Nascere, entre los meses de enero a julio de 2019. Se incluyeron pacientes con pobre respuesta ovárica según los criterios de Bologna y con indicación de PGT-A. Las estimulaciones en fase folicular y lútea se efectuaron con antagonista de la GnRH y FSHr/LHr (2:1) a partir del día 3 del ciclo y 5 días después de la primera recuperación de los ovocitos. Para completar el proceso de maduración ovocitaria se utilizaron análogos de GnRH, se tomó una biopsia de trofoectodermo en día 5-7. RESULTADOS: Se estudiaron 20 pacientes. Al comparar la fase folicular con la lútea la tasa de fertilización fue de 79% (IC95%: 29-46) vs 55% (IC95%: 34-53), la tasa de blastocistos 42% (IC95%: 19-44) vs 45% (IC95%: 24-55) y la tasa de blastocistos euploides 100% (IC95%: 44-53) vs 70% (IC95%: 38-46), respectivamente. Solo la tasa de recuperación de ovocitos en metafase II mostró diferencias significativas entre ambas fases 40% (IC95%: 18-37) vs 59% (IC95%: 31-59), p = 0.0333 en la fase folicular y lútea, respectivamente. CONCLUSIONES: La estimulación ovárica bifásica (folicular-lútea), en el mismo ciclo menstrual (DuoStim), resultó en mayor tasa de recuperación de ovocitos en metafase II durante la fase lútea. Sin embargo, las tasas de desarrollo embrionario a día 5-6 (blastocistos) y de embriones euploides fueron similares entre ambas fases.

Abstract: OBJECTIVE: Euploid blastocyst rate comparison between ovarian stimulation in follicular vs luteal phase performed in the same menstrual cycle in patients with poor ovarian response. MATERIALS AND METHODS: Clinical, prospective and comparative study conducted at Centro de Reproducción Arcos S.C., "Nascere", during january-july, 2019. Patients with PGT-A indication and poor ovarian response according to Bologna criteria were included. Under a short GnRH-antagonist protocol, stimulations, both in follicular and luteal phase were performed using rFSH/rLH (2:1) from day 3 of the cycle and 5 days after the first oocyte retrieval. In addition, ovulation trigger with an GnRH agonist was used, finally, on day 5-6 of embryo development, trophoctoctoderm biopsy was performed. RESULTS: In this study, 20 patients were included; when comparing follicular phase vs luteal phase, we found that fertilization rate was 79% (95%CI 29-46) vs 55% (95%CI 34-53), blastocysts rate was 42% (95%CI 19-44) vs 45% (95%CI 24-55) and euploid embryo rate was 100% (95%CI 44-53) vs 70% (95%CI 38-46). Only the oocyte recovery rate in metaphase II showed significant differences between both phases 40% (IC 95% 18-37) vs 59% (IC 95% 31-59), p=0.0333. CONCLUSION: Biphasic ovarian stimulation (follicular/ luteal) in the same menstrual cycle (DuoStim) resulted in a higher metaphase II ooctye recovery rate during the luteal phase in comparison with the follicular phase. However, the rates of blastocysts and euploid blastocysts were similar between both phases.

A prospective randomized controlled trial showing efficacy of luteal phase low molecular weight heparin in fresh non-donor IVF/ICSI cycles in women with previous implantation failures

Background: Implantation failure is a major challenge in in-vitro fertilization (IVF) cycles. The present study was undertaken to determine the immunomodulatory effects of heparin in patients with previous implantation failures undergoing assisted reproductive techniques (ART).Methods: This was a prospective randomized controlled trial with sample size of 100 patients who had history of at least one previously failed IVF/ICSI. Study group of 50 patients received heparin and 50 patients in control group received routine luteal phase support.Results: Primary outcome of the study was implantation rate (IR) which was 11.03% in the study group was and 5.48% in the control group (p=0.08). Biochemical pregnancy rate and clinical pregnancy rate in the study group was 18% and 12% in the control group (p=0.401). Calculated live birth was 5.15% and 3.42% in the study and control groups respectively (p=0.562). 11 babies were taken home from the study group and 6 from the control group (p=0.18).Conclusions: The result of this pilot study showed relative increase in implantation rates (IR) suggesting beneficial effects of heparin in patients with repeated implantation failures. Although these changes are not statistically significant, the presence of an increasing trend in all the outcome parameters signify the possible benefits of heparin proving for the present study hypothesis.

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.

Do food intake and food cravings change during the menstrual cycle of young women? / A ingestão de alimentos e os desejos por comida mudam durante o ciclo menstrual das mulheres jovens?

Abstract Objective The aim of the present study was to assess the anthropometric measures, food intake and food cravings during the menstrual cycle of undergraduate students of the faculty of nutrition. Methods A cross-sectional study was performed with 27 students from a public university in the state of Mato Grosso do Sul, Brazil, who had their food intake evaluated through a 24-hour food recall, their nutritional status evaluated based on anthropometric measures, and food cravings evaluated using the Food Desire Questionnaire. Data were collected during an evaluation in the follicular phase (between the 5th and the 9th day of the menstrual cycle) and another in the luteal phase (LP) (between the 20th and the 25th day of the menstrual cycle). For food intake variables, the analysis of variance (ANOVA) test was used, followed by the Tukey test. The Mann-Whitney test was used for the analysis of food cravings, considering a significance level of 5% (p< 0.05). Results The desire for foods rich in sugar, salt, and fat, such as chocolate, pastries, snacks and desserts were higher (p< 0.05) during the premenstrual period, although it did not reflect neither a higher energy intake nor an alteration in the distribution of macronutrients. A higher intake of carbohydrates, proteins, fibers, and calcium was observed during the LP; however, without statistical difference between the groups. There were no differences either in the intake of any food group or in the anthropometric measurements (p> 0.05). Conclusion Food cravings of nutrition students differed between the phases of the menstrual cycle; however, with no difference in food intake and in anthropometric measures.

Resumo Objetivo Verificar alterações de medidas corporais, consumo e desejos alimentares durante o ciclo menstrual de acadêmicas de nutrição. Métodos Estudo transversal com 27 estudantes de uma universidade pública do Mato Grosso do Sul, as quais tiveram seu consumo alimentar avaliado por meio de recordatório alimentar de 24 horas, estado nutricional avaliado com base em medidas antropométricas, e desejos alimentares avaliados utilizando-se o Questionário de Desejo Alimentar. Os dados foram coletados durante uma avaliação na fase folicular (entre o 5° e o 9° dia do ciclo menstrual) e outra na fase lútea (entre o 20° e o 25° dia do ciclo menstrual). Para as variáveis de consumo alimentar, utilizou-se o teste análise de variância (ANOVA, na sigla em inglês), seguido pelo teste de Tukey. Já para a análise dos desejos alimentares, utilizou-se o teste de Mann-Whitney. Foi considerado o nível de significância de 5% (p< 0,05). Resultados Os desejos por alimentos ricos em açúcar, sal e gordura, como chocolates, produtos de pastelaria, lanches e sobremesas foram maiores (p< 0,05) no momento pré-menstrual, apesar de não refletirem em maior consumo energético e tampouco em alteração na distribuição de macronutrientes. Observou-se maior consumo de carboidratos, proteínas, fibras e cálcio na fase lútea; no entanto, sem diferença estatística entre os grupos. Não foram encontradas diferenças no consumo de nenhum grupo alimentar, tampouco nas medidas antropométricas (p> 0,05). Conclusão Os desejos alimentares das acadêmicas de nutrição diferiram entre as fases; no entanto, sem diferença no consumo alimentar e nas medidas corporais.

Resultados de un programa de reproducción asistida con transferencia de embriones en día 4 / Results of an assisted reproduction program with embryo transfer on day 4

Resumen OBJETIVO: Conocer las repercusiones en la reproducción de la aplicación de un programa de trasferencia embrionaria en día 4 y compararlas con trasferencias en día 3 y día 5. MATERIALES Y MÉTODOS: Estudio prospectivo efectuado en parejas a quienes se aplicó un procedimiento de FIV-ICSI entre marzo de 2015 y julio de 2017. Criterios de inclusión: pacientes de todas las edades, ciclos capturados y trasferidos en fresco y con todos los factores de infertilidad. Criterios de exclusión: casos de ovodonación, ciclos en donde no hubiera embriones a trasferir y ciclos en donde la trasferencia embrionaria fue difícil. Para fines de estudio la población se dividió en tres grupos: grupo A con trasferencia en día 3; grupo B con trasferencia en día 4 y grupo C con trasferencia en día 5. El soporte de fase lútea para los tres grupos fue con progesterona por vía vaginal durante 14 días. Se evaluaron las tasas de embarazo por día de tras-ferencia con el número de embarazos clínicos respecto del número de trasferencias efectuadas y los resultados se compararon con c2; se consideró diferencia significativa el valor de p < 0.05. RESULTADOS: Se estudiaron 306 parejas. Grupo A: 205 pacientes trasferidas en día 3; grupo B: 62 pacientes trasferidas en día 4; grupo C: 39 pacientes trasferidas en día 5. Se encontró una diferencia significativa (p = 0.035) entre la tasa de embarazo en día 3 y 4 para pacientes mayores de 40 años (11.4 y 31.6%, respectivamente). En todas las edades se observó una tendencia al incremento en la tasa de embarazo cuando la trasferencia embrionaria se llevó a cabo en día 4. CONCLUSIONES: La trasferencia embrionaria en día 4 de desarrollo puede considerarse una opción más. En este ensayo hubo mejores resultados con respecto a las trasferencias efectuadas en día 3. Es una alternativa viable en trasferencias efectuadas en día 5 con tasas de embarazo muy similares y, en este estudio, incluso mayor.

Abstract OBJECTIVE: To know the reproductive results in an embryo transfer program on day 4 and compare them with transfers in D3 and D5 MATERIALS AND METHODS: A prospective analysis comprised a period from March 2015 to July 2017, with 306 couples undergoing an IVF / ICSI procedure and who met the inclusion criteria (patients of all ages, cycles captured and transferred in fresh and patients with all the factors of infertility) and exclusion (cases of ovodonation, cycles in which there were no embryos to be transferred and cycles in which embryo transfer was difficult). The population was divided into 3 groups: Group A with transferred on day 3; Group B with transferred on day 4) and Group C with transferred on day 5 (TE D5). The luteal phase support for the 3 groups was with progesterone vaginally for 14 days. Pregnancy rates per transfer day were evaluated with the number of clinical pregnancies regarding the number of transfers made and comparing the results with a chi-square test considering significant differences with p < 0.05. RESULTS: We analyze 306 couples. Group A with 205 patients transferred on day 3 (TE D3); Group B with 62 patients transferred on day 4 (TE D4) and Group C with 39 patients transferred on day 5 (TE D5). A significant difference (p = 0.035) was found between the pregnancy rate on day 3 and 4 for patients over 40 years of age (11.4% and 31.6% respectively), however, an increase tendency was observed at all ages. in the pregnancy rate when the embryo transfer takes place on day 4. CONCLUSIONS: The embryo transfer on day 4 of development can be considered as one more option, to present better results with respect to the transfers made on day 3, and a very viable alternative in transfers made in D5 with very similar pregnancy rate and in this even greater study.

Study on the changes of gonadotropin releasing hormone agonist in pinopodes / 中华妇产科杂志

Objective To study the changes of gonadotropin releasing hormone agonist (GnRH-a) in pinopodes during luteal phase and to explore the possible mechanism of GnRH-a in luteal phase support of assisted reproductive technology (ART).Methods Totally 40 primary infertility women who were treated with ART due to male factors were enrolled,according to the order of the group they were randomly divided into experimental group and control group.On the 7th day after ovulation,the experimental group received a subcutaneous injection of 0.1 mg of GnRH-a,while the control group received a subcutaneous injection of placebo only (0.9％ salinc 2 ml),3 days later they came to the clinic again.Serum estradiol and progesterone levels were measured before and after treatment in each group.Pinopodes were collected for electron microscopic examination.Levels of ER and PR were detected by western blot.Results (1) There was no significant difference between the experimental group and the control group in the estrogen level before and after the treatment (all P＞0.05).The level of progesterone in the experimental group after treatment [(66.8± 14.9) nmol/L] was significantly higher than that before treatment(P＜0.05);also significantly higher than the same period of the control group (P＜0.05).(2) There was no significant difference in the expression of ER protein in the experimental group before and after treatment (P＞0.05).The expression of PR in the experimental group after treatment was significantly lower than that before treatment (P＜0.05);also lower than the same period of the control group (P＜0.05).(3) Expression amount of pinopodes in the experimental group after treatment was significantly higher than that before treatment [65％ (13/20) versus 25％ (5/20),P＜ 0.05],and the development trend was more mature [the percentage of maturation:75％ (15/20) versus 35％ (7/ 20),P＜0.05].Expression amount of pinopodes after treatment and the percentage of maturation in the experimental group were significantly higher than those in the same period of control group (P＜0.05).Conclusion GnRH-a in luteal phase support may play a role through the corpus luteum,which may promote the secretion of progesterone,downregulation of PR expression,promote the growth of pinopodes,and improve the endometrial receptivity.

Live birth rates and safety profile using dydrogesterone for luteal phase support in assisted reproductive techniques

<p><b>INTRODUCTION</b>Assisted reproductive techniques (ARTs) result in a deficient luteal phase, requiring the administration of intramuscular, intravaginal or oral exogenous progesterone. Dydrogesterone, an oral retroprogesterone with good bioavailability, has been used in assisted reproductive cycles with outcomes that are comparable to those of vaginal or intramuscular progesterone. However, there are limited reviews on its use for luteal phase support in ARTs, in terms of pregnancy outcomes and associated fetal anomalies. This study aimed to review the live birth rates and associated fetal anomalies of women who were given dydrogesterone for luteal phase support in assisted reproductive cycles at a tertiary hospital in Singapore.</p><p><b>METHODS</b>This retrospective descriptive study included 1,050 women who underwent in vitro fertilisation/intracytoplasmic sperm injection at the Centre for Assisted Reproduction of Singapore General Hospital between 2000 and 2011. The women were given dydrogesterone for luteal phase support. The main outcome measures were rates of pregnancy, live birth, miscarriage and fetal anomalies.</p><p><b>RESULTS</b>The pregnancy and live birth rates were 34.7% and 27.7%, respectively. Among those who achieved pregnancy, 17.0% miscarried, 0.8% had ectopic pregnancies and 0.3% had molar pregnancies. Fetal anomalies were detected in 1.9% of pregnancies, all of which were terminated by choice.</p><p><b>CONCLUSION</b>Since the outcomes of dydrogesterone are comparable to those of intramuscular and vaginal progesterone, it is a reasonable option to provide luteal phase support for women who are uncomfortable with injections or vaginal insertions. Randomised controlled studies are needed to determine the optimal dosage of dydrogesterone for luteal phase support in ARTs.</p>

Influence of Hormonal Changes on Audiologic Examination in Normal Ovarian Cycle Females: An Analytic Study

Abstract Introduction There is only limited information from previous studies that suggest that auditory function may be influenced by hormones. Recent advances in the field have exposed the potential role of hormones in modulating the auditory system. Objective This study aims to investigate the relationship between menstrual cycle and outer hair cell function with audiological examination. Methods This is an analytic study with a cross-sectional design. The sampling was a systematic random sampling. We found 49 women with normal menstrual cycle and collected their data through interviews, physical examination, and examination of the ear, with otoscopic and other routine otorhinolaryngology examinations. We evaluated Tympanometry, distortion-product otoacoustic emissions (DPOAE), and pure tone audiometry. Results We found the audiometric threshold worse in the follicular phase than other phases at 4000 Hz of the right ear, and in the ovulation was found best than any other phases at 1000 Hz of the left ear with significant difference. We found significant difference of DPOAE between ovulation time and follicular phase at 3000 Hz and 1000 Hz in the left ear and between ovulation and luteal phased at 2000 Hz, 3000 Hz and 5000 Hz in the right ear and at 1000 Hz in the left ear with p< 0.05. Conclusion The result of this study showed that only a small part of audiometry threshold had a significant difference between each menstrual phase. In other words, we found no correlation between menstrual and audiometry threshold. Nonetheless, there is a correlation between menstrual cycle phase and DPOAE amplitude.

The applications of double stimulations and mild ovarian stimulation with GnRH-antagonist in patients with decreased ovarian reserve / 安徽医科大学学报

Objective To discuss the value of double stimulations and mild ovarian stimulation combined with Gn-RH-antagonist in patients with decreased ovarian reserve receiving in vitro fertilization and embryo transfer ( IVF-ET) . Methods 283 patients with decreased ovarian reserve who accepted in vitro fertilization were analyzed retro-spectively. 204 cases accepted double stimulations and 79 cases accepted mild ovarian stimulation combined with GnRH-antagonist, compared the outcomes of the two protocols. Results The average number of oocytes retrieved, viable embryos,high-quality embryos,consumption and duration of Gn,the serum progesterone( P) level on trigger day in the luteal phase were significantly higher than those in follicular phase. The serum luteinizing hormone( LH) level on trigger day was lower than that in follicular phase. The average number of oocytes retrieved,high-quality embryos,consumption and duration of gonadotropins( Gn) in mild stimulation combined with GnRH-antagonist were higher than those in follicular phase. LH level on trigger day was lower than those in follicular phase, while the numbers of viable embryos were similar. The consumption and duration of Gn in the luteal phase were higher than in stimulation combined with GnRH-antagonist, and there were no differences in the average number of oocytes re-trieved,viable embryos,high-quality embryos between the two groups. The cycle cancellation rate, available rate of oocytes and embryos were similar between the controlled ovarian hyperstimulation. The available rate of embryos in double stimulations was higher than mild ovarian stimulation combined with GnRH-antagonist,and the abortion rate was lower. Conclusion Controlled ovarian hyperstimulation during luteal phase can get better outcomes in patients with decreased ovarian reserve,double stimulations in the same menstrual cycle shortens the treatment time of IVF-ET,and it is a feasible method for patients with decreased ovarian reserve.

The levels of estradiol decline in the early luteal phase predictes the outcomes of in-vitro fertilization / 实用医学杂志

Objective To explore the role of estradiol decline in the early luteal phase (the 2nd day after oocyte retrieval) in the prediction of in-vitro fertilization outcomes. Methods A total of 236 cases under in vitro fertilization-embryo transfer (IVF-ET)/ intracytoplasmic sperm injection-embryo transfer(ICSI-ET) cycles were included in this retrospective study of their medical records. The cases were divided into three groups according to the levels of estradiol decline on the 2nd day following OPU: group A (n = 70) with the decline rate of less than 70%, group B (n=114) with the decline rate of 70%~80%and group C (n=52) at the decline rate of more than 80%. The comparisons were done among the three groups in terms of the number of oocyte retrieval, the rate of fertilization, the rate of best oocytes and the rate of miscarriage. Results There were no significant differences statistically in the number of oocyte retrieval, the rate of fertilization, the rate of best oocytes and the rate of miscarriage (P > 0.05). But the rates of clinical pregnancy rate in groups A and B were significantly higher than that in group C (68.6% and 68.4% vs. 44.2%) (P < 0.05). Conclusion The levels of estradiol declines in the early luteal phase may be important in the prediction of IVF outcomes.

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 .