Impact of low serum progesterone levels on the day of embryo transfer on pregnancy outcome: a prospective cohort study in artificial cycles with vaginal progesterone

2020 ◽  
Author(s):  
Elena Labarta ◽  
Giulia Mariani ◽  
Stefania Paolelli ◽  
Cristina Rodriguez-Varela ◽  
Carmina Vidal ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Cohort Study ◽  
Embryo Transfer ◽  
Prospective Cohort ◽  
Independent Factor ◽  
Ongoing Pregnancy ◽  
Multivariate Logistic Regression ◽  
Serum Progesterone ◽  
Endometrial Preparation ◽  
Day Of Embryo Transfer

Abstract STUDY QUESTION Is there a serum progesterone (P) threshold on the day of embryo transfer (ET) in artificial endometrium preparation cycles below which the chances of ongoing pregnancy are reduced? SUMMARY ANSWER Serum P levels <8.8 ng/ml on the day of ET lower ongoing pregnancy rate (OPR) in both own or donated oocyte cycles. WHAT IS KNOWN ALREADY We previously found that serum P levels <9.2 ng/ml on the day of ET significantly decrease OPR in a sample of 211 oocyte donation recipients. Here, we assessed whether these results are applicable to all infertile patients under an artificial endometrial preparation cycle, regardless of the oocyte origin. STUDY DESIGN, SIZE, DURATION This prospective cohort study was performed between September 2017 and November 2018 and enrolled 1205 patients scheduled for ET after an artificial endometrial preparation cycle with estradiol valerate and micronized vaginal P (MVP, 400 mg twice daily). PARTICIPANTS/MATERIALS, SETTING, METHODS Patients ≤50 years old with a triple-layer endometrium ≥6.5 mm underwent transfer of one or two blastocysts. A total of 1150 patients treated with own oocytes without preimplantation genetic testing for aneuploidies (PGT-A) (n = 184), own oocytes with PGT-A (n = 308) or donated oocytes (n = 658) were analyzed. The primary endpoint was the OPR beyond pregnancy week 12 based on serum P levels measured immediately before ET. MAIN RESULTS AND THE ROLE OF CHANCE Women with serum P levels <8.8 ng/ml (30th percentile) had a significantly lower OPR (36.6% vs 54.4%) and live birth rate (35.5% vs 52.0%) than the rest of the patients. Multivariate logistic regression showed that serum P < 8.8 ng/ml was an independent factor influencing OPR in the overall population and in the three treatment groups. A significant negative correlation was observed between serum P levels and BMI, weight and time between the last P dose and blood tests and a positive correlation was found with age, height and number of days on HRT. Multivariate logistic regression showed that only body weight was an independent factor for presenting serum P levels <8.8 ng/ml. Obstetrical and perinatal outcomes did not differ in patients with ongoing pregnancy regardless of serum P levels being above/below 8.8 ng/ml. LIMITATIONS, REASONS FOR CAUTION Only women with MVP were included. Extrapolation to other P administration forms needs to be validated. WIDER IMPLICATIONS OF THE FINDINGS This study identified the threshold of serum P as 8.8 ng/ml on the day of ET for artificial endometrial preparation cycles necessary to optimize outcomes, in cycles with own or donated oocytes. One-third of patients receiving MVP show inadequate levels of serum P that, in turn, impact the success of the ART cycle. Monitoring P levels in the mid-luteal phase is recommended when using MVP to adjust the doses according to the needs of the patient. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER NCT03272412.

Individualised luteal phase support in artificially prepared frozen embryo transfer cycles based on serum progesterone levels: a prospective cohort study

2021 ◽  
Author(s):  
Manuel Álvarez ◽  
Sofía Gaggiotti-Marre ◽  
Francisca Martínez ◽  
Lluc Coll ◽  
Sandra García ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
Luteal Phase ◽  
Frozen Embryo Transfer ◽  
Ongoing Pregnancy ◽  
Serum Progesterone ◽  
Endometrial Preparation ◽  
Group 2 ◽  
Group 1

Abstract STUDY QUESTION Does an individualised luteal phase support (iLPS), according to serum progesterone (P4) level the day prior to euploid frozen embryo transfer (FET), improve pregnancy outcomes when started on the day previous to embryo transfer? SUMMARY ANSWER Patients with low serum P4 the day prior to euploid FET can benefit from the addition of daily subcutaneous P4 injections (Psc), when started the day prior to FET, and achieve similar reproductive outcomes compared to those with initial adequate P4 levels. WHAT IS KNOWN ALREADY The ratio between FET/IVF has spectacularly increased in the last years mainly thanks to the pursuit of an ovarian hyperstimulation syndrome free clinic and the development of preimplantation genetic testing (PGT). There is currently a big concern regarding the endometrial preparation for FET, especially in relation to serum P4 levels around the time of embryo transfer. Several studies have described impaired pregnancy outcomes in those patients with low P4 levels around the time of FET, considering 10 ng/ml as one of the most accepted reference values. To date, no prospective study has been designed to compare the reproductive outcomes between patients with adequate P4 the day previous to euploid FET and those with low, but restored P4 levels on the transfer day after iLPS through daily Psc started on the day previous to FET. STUDY DESIGN, SIZE, DURATION A prospective observational study was conducted at a university-affiliated fertility centre between November 2018 and January 2020 in patients undergoing PGT for aneuploidies (PGT-A) IVF cycles and a subsequent FET under hormone replacement treatment (HRT). A total of 574 cycles (453 patients) were analysed: 348 cycles (leading to 342 euploid FET) with adequate P4 on the day previous to FET, and 226 cycles (leading to 220 euploid FET) under iLPS after low P4 on the previous day to FET, but restored P4 levels on the transfer day. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall we included 574 HRT FET cycles (453 patients). Standard HRT was used for endometrial preparation. P4 levels were measured the day previous to euploid FET. P4 > 10.6 ng/ml was considered as adequate and euploid FET was performed on the following day (FET Group 1). P4 < 10.6 ng/ml was considered as low, iLPS was added in the form of daily Psc injections, and a new P4 analysis was performed on the following day. FET was only performed on the same day when a restored P4 > 10.6 ng/ml was achieved (98.2% of cases) (FET Group 2). MAIN RESULTS AND THE ROLE OF CHANCE Patient’s demographics and cycle parameters were comparable between both euploid FET groups (FET Group 1 and FET Group 2) in terms of age, weight, oestradiol and P4 levels and number of embryos transferred. No statistically significant differences were found in terms of clinical pregnancy rate (56.4% vs 59.1%: rate difference (RD) −2.7%, 95% CI [−11.4; 6.0]), ongoing pregnancy rate (49.4% vs 53.6%: RD −4.2%, 95% CI [−13.1; 4.7]) or live birth rate (49.1% vs 52.3%: RD −3.2%, 95% CI [−12; 5.7]). No significant differences were also found according to miscarriage rate (12.4% vs 9.2%: RD 3.2%, 95% CI [−4.3; 10.7]). LIMITATIONS, REASONS FOR CAUTION Only iLPS through daily Psc was evaluated. The time for Psc injection was not stated and no serum P4 determinations were performed once the pregnancy was achieved. WIDER IMPLICATIONS OF THE FINDINGS Our study provides information regarding an ‘opportunity window’ for improved ongoing pregnancy rates and miscarriage rates through a daily Psc injection in cases of inadequate P4 levels the day previous to FET (P4 < 10.6 ng/ml) and restored values the day of FET (P4 > 10.6 ng/ml). Only euploid FET under HRT were considered, avoiding one of the main reasons of miscarriage and implantation failure and overcoming confounding factors such as female age, embryo quality or ovarian stimulation protocols. STUDY FUNDING/COMPETING INTEREST(S) No external funding was received. B.C. reports personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, IBSA and Gedeon Richter outside the submitted work. N.P. reports grants and personal fees from MSD, Merck Serono, Ferring Pharmaceuticals, Theramex and Besins International and personal fees from IBSA and Gedeon Richter outside the submitted work. The remaining authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER NCT03740568.

Donepezil Combined with DL-3-n-Butylphthalide Delays Cognitive Decline in Patients with Mild to Moderate Alzheimer’s Disease: A Multicenter, Prospective Cohort Study

2021 ◽  
Vol 80 (2) ◽  
pp. 673-681
Author(s):  
Jin Wang ◽  
Xiaojuan Guo ◽  
Wenhui Lu ◽  
Jie Liu ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Cohort Study ◽  
Prospective Cohort ◽  
Daily Living ◽  
Multivariate Logistic Regression Analysis ◽  
Multivariate Logistic Regression ◽  
Significant Difference

Background: Vascular factors and mitochondria dysfunction contribute to the pathogenesis of Alzheimer’s disease (AD). DL-3-n-butylphthalide (NBP) has an effect in protecting mitochondria and improving microcirculation. Objective: The aim was to investigate the effect of donepezil combined NBP therapy in patients with mild-moderate AD. Methods: It was a prospective cohort study. 92 mild-moderate AD patients were classified into the donepezil alone group (n = 43) or the donepezil combined NBP group (n = 49) for 48 weeks. All patients were evaluated with Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-cog), Clinician’s Interview-Based Impression of Change plus caregiver input (CIBIC-plus), Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI) every 12 weeks. All patients were monitored for adverse events (AEs). The efficacy was analyzed using multivariate logistic regression analysis. Results: The multivariate logistic regression analysis showed that the changes of ADAS-cog score (OR = 2.778, 95% CI: [1.087, 7. 100], p = 0.033) and ADCS-ADL score (OR = 2.733, 95% CI: [1.002, 7.459], p = 0.049) had significant difference between donepezil alone group and donepezil combined NBP group, while the changes of NPI (OR = 1.145, 95% CI: [0.463, 2.829], p = 0.769), MMSE (OR = 1.563, 95% CI: [0.615, 3.971], p = 0.348) and CIBIC-plus (OR = 2.593, 95% CI: [0.696, 9.685], p = 0.156) had no significant difference. The occurrence of AEs was similar in the two groups. Conclusion: Over the 48-week treatment period, donepezil combined NBP group had slower cognitive decline and better activities of daily living in patients with mild to moderate AD. These indicated that the multi-target therapeutic effect of NBP may be a new choice for AD treatment.

P–411 Does subcutaneous progesterone (SC-P) administration eliminate the necessity of serum progesterone level monitoring in frozen embryo transfer (FET) cycles?

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
F K Boynukalin ◽  
R Abalı ◽  
M Gultomruk ◽  
B Demir ◽  
Z Yarkiner ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Clinical Outcomes ◽  
Embryo Transfer ◽  
Endometrial Thickness ◽  
Hormone Replacement ◽  
Pregnancy Rates ◽  
Ongoing Pregnancy ◽  
Ongoing Pregnancy Rate ◽  
Serum Progesterone ◽  
Female Age

Abstract Study question Does SC-P provide similar ongoing pregnancy rates (OPRs) as intramuscular progesterone(IM-P) in hormone replacement therapy (HRT)-FET cycles and do serum progesterone (P) levels on FET day effect on pregnancy outcome? Summary answer: SC-P administration had similar OPR compared to IM-P in HRT-FET cycles. In SC-P group embryo transfer(ET) day P found to be insignificant factor for outcome. What is known already Different P routes can be used in HRT-FET cycles such as vaginal P, IM-P and recently SC-P. Only retrospective studies evaluated the comparison of SC-P with other routes in HRT-FET cycles. Here, we assessed prospectively whether SC-P is effective for HRT-FET cycles. Previous studies reported that serum P levels on ET day after vaginal P administration clinical outcomes were closely correlated. The correlation between serum P after IM-P administration and clinical outcomes were conflicting. In addition, there is lack of data on the serum P levels after SC-P administration. Serum P levels on ET day were evaluated in this study. Study design, size, duration This prospective cohort study was performed between July 1-October 31 2020, enrolled 224 patients scheduled for HRT-FET cycles with SC-P(25 mg twice daily) or IM-P(50 mg once daily). The route of P was decided according to the patient’s eligibility to hospital. First FET cycle was included after freeze-all cycles for each patients. Female age>35, PGT-A cycles, cleavage ET, >1 ET, patients with uterine pathology and hydrosalpinx, FET with surplus embryos, endometrial thickness<7mm were excluded. Participants/materials, setting, methods Female age ≤ 35 years old with a triple-layer endometrium >7 mm underwent transfer of single blastocysts after the first ET after freeze-all cycles. The indications for freeze-all were ovarian hyperstimuation syndrome and trigger day P level>1.5 ng/ml. 224 patients were eligible for study; 133 in SC-P group and 91 in IM-P group.The primary endpoint was the ongoing pregnancy rate (OPR) beyond pregnancy week 12. Main results and the role of chance The demographic, cycle, embryologic characteristics were similar between groups. The median circulating P levels on the day of ET were 19.92(15.195–27.255)ng/
ml and 21(16.48–28)ng/ml in the SC-P and IM-P groups,(p = 0.786). The clinical pregnancy rates [86/133(64.7%) vs 57/91(62.6%);p=0.757], miscarriage rates [21/86(24.4%) vs 10/57(17.5%) ;p=0.329], and OPR [65/133 (48.9%) vs 47/91(51.6%); p = 0.683] were comparable between the SC-P and IM-P. Binary logistic regression was performed for ongoing pregnancy as the dependent factor blastocyst morphology was found to be the only significant independent prognostic factor (p = 0.006), whereas the route of P was insignificant. In the SC-P and IM-P 
groups, the effect of ET day P levels were divided into quartiles(Q) to evaluate the effect on ongoing pregnancy. In SC-P group OPR were similar in four Q [Q1:33.3%(11/33),Q2:50%(17/34),Q3:60.6%(20/33),Q4:51.5%(17/33) (p = 0.1)].For IM-P group; Q1 had a significantly reduced OPR than Q2, Q3, Q4. [26.1%(6/23),65.2%(15/23),54.5%(12/22) and 60.9%(14/23), p = 0.031]. Logistic regression analysis for OP was performed separately in SC-P group and IM-P group. Although in SC-P group, ET day P levels was not found to be a significant factor, in IM-P ET day P level was found to be an independent factor for OP in IM-P group (Q1vs Q2+Q3+Q4; OR: 8,178 95% CI: [1.387–48.223] p:0.02). . Limitations, reasons for caution Although this study has the advantage of being prospective and in a homogenous study population, randomized controlled trials are warranted to evaluate the effectiveness of SC-P to other routes of P. Extrapolation to unselected populations of this study is needed. Wider implications of the findings: Assignment of threshold of serum P on the day of ET for HRT-FET cycles to optimize outcomes is critical for every route of P. Regarding these results, individual luteal phase for HRT-FET cycles can improve IVF outcome. Trial registration number None

scholarly journals Nomogram-Based Prediction of the Risk of Macrosomia: A Prospective Cohort Study in a Chinese Population

2021 ◽  
Author(s):  
Jing Du ◽  
Sanbao Chai ◽  
Xin Zhao ◽  
Jianbin Sun ◽  
Ning Yuan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Operating Characteristic ◽  
Multivariate Logistic Regression Analysis ◽  
Maternal Factors ◽  
Multivariate Logistic Regression ◽  
History Of

Abstract Objective: This study aimed to establish a nomogram for predicting the risk of macrosomia in early pregnancy.Methods: We performed a prospective cohort study involving 1,549 pregnant women. According to the birth weight of newborn, the subjects were divided into two groups: macrosomia group and non-macrosomia group. Multivariate logistic regression was used to analyze the risk factors for macrosomia.Results: The prevalence of macrosomia was 6.13% (95/1549) in our hospital. Multivariate logistic regression analysis showed the risk factors of macrosomia were prepregnancy overweight (OR: 2.126, 95% CI: 1.181-3.826)/obesity (OR: 3.536, 95% CI: 1.555-8.036), multiparity (OR:1.877, 95% CI: 1.160-3.039), the history of macrosomia (OR: 36.971, 95% CI: 19.903-68.674), the history of GDM/DM (OR: 2.285, 95% CI: 1.314-3.976), the higher levels of HbA1c (OR: 1.763, 95% CI: 1.004-3.097) and TC (OR: 1.360, 95% CI: 1.004-1.842). A nomogram was developed for predicting macrosomia based on maternal factors related to the risk of macrosomia in early pregnancy. The area under the receiver operating characteristic (ROC) curve of the nomogram was 0.807 (95% CI: 0.755–0.859), the sensitivity and specificity of the model were 0.716 and 0.777, respectively.Conclusion: The nomogram model provides an accurate mothed for clinicians to early predict macrosomia.

scholarly journals Independent predictors for longer radiographic resolution in patients with refractoryMycoplasma pneumoniaepneumonia: a prospective cohort study

BMJ Open ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. e023719 ◽  
Author(s):  
Lizhen Huang ◽  
Xia Huang ◽  
Wujiang Jiang ◽  
Rong Zhang ◽  
Yongdong Yan ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Cohort Study ◽  
Prospective Cohort Study ◽  
Prospective Cohort ◽  
Chest Radiographs ◽  
C Reactive Protein ◽  
Multivariate Logistic Regression ◽  
Reactive Protein ◽  
Bronchial Mucus ◽  
Plug Formation

ObjectivesTo examine prospectively the radiographic clearance of refractoryMycoplasma pneumoniaepneumonia (RMPP) in immunocompetent children, and to identify independent predictors of time to complete radiographic resolution in patients with RMPP.DesignA prospective cohort study.SettingChildren’s Hospital of Soochow University, China.ParticipantsA total of 187 patients with RMPP treated with bronchoscopy were prospectively enrolled in the study between January 2012 and December 2015.MethodsSerial chest radiographs were obtained after discharge every 4 weeks up to a maximum of 24 weeks after diagnosis or until large infiltration on chest radiographs had resolved. Multivariate logistic regression was performed to identify independent predictors of time to complete radiographic resolution.ResultsOf the 187 patients with RMPP, bronchial mucus plug formation was detected in 73 (39.0%). C reactive protein (CRP) ≥50 mg/L, lactate dehydrogenase (LDH) ≥480 U/L, total fever duration ≥10 days and presence of mucus plugs were associated with longer time to radiographic clearance (all p<0.01). Compared with children without mucus plugs, those with mucus plugs were significantly more likely to have longer time to radiographic clearance (adjusted OR: 11.5; 95% CI 2.5 to 45.7; p<0.01).ConclusionClinicians might use duration of fever, CRP, LDH and presence of mucus plugs as parameters to identify children at a longer time to radiographic clearance in patients with RMPP.

scholarly journals Association between serum progesterone levels on the day of frozen-thawed embryo transfer and pregnancy outcomes after artificial endometrial preparation

2020 ◽  
Author(s):  
Jing Zhu ◽  
Qianqian Zhu ◽  
Jialyu Huang ◽  
Meiting Qiu ◽  
Yanwen Zhu ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Embryo Transfer ◽  
Pregnancy Outcomes ◽  
Luteal Phase ◽  
Serum Progesterone ◽  
Endometrial Preparation ◽  
Vaginal Progesterone ◽  
Frozen Thawed Embryo Transfer ◽  
Thawed Embryo Transfer

Abstract Background Previous studies have examined that a range of optimal serum P level during the implantation period was associated with optimal live birth rates. However, those results obtained with vaginal or intramuscular route of progesterone administration for LPS alone. Is there a relationship between the serum progesterone (P) on the day of frozen-thawed embryo transfer (FET) with the likelihood of a live birth(LB) in artificial cycles(AC) when using a combination of oral dydrogesterone and vaginal progesterone for luteal phase support (LPS)? Methods This was a retrospective study of 3659 FET cycles with artificial endometrial preparation in a Chinese tertiary-care academic medical centre from January 2015 to February 2017. Endometrial preparation was performed using estradiol (E 2 ) valerate (Fematon-red tablets) 8 mg/d beginning on day 3 of the cycle, followed by administration of P both orally (40 mg dydrogesterone and 8 mg E 2 twice per day, Fematon-yellow tablets) and vaginally (400 mg/d; Utrogestan). The primary endpoint was LBR. The association between the serum P level on the embryo transfer day and pregnancy outcomes was evaluated by univariable and multivariable logistic regression analysis. Results Mean serum P on the day of embryo transfer was 10.30 ± 3.88 ng/ml (percentiles: 25, 7.9; 50, 9.7; 75, 12.1). The LBRs according to the serum P quartiles were as follows: Q1, 35.7%; Q2, 37.4%; Q3, 39.1%; and Q4: 38.9%. Logistic regression analysis showed that the odds of a LB were not significantly different between the low (P <7.9 ng/mL) and high (P ≥7.9 ng/mL) progesterone groups before or after adjustment (crude odds ratio [OR] = 0.89, 95% confidence interval [CI]: 0.76-1.04; adjusted OR = 0.89, 95% CI: 0.75-1.04). Conclusions The present study suggests that the serum P levels on the day of ET do not correlate with the likelihood of a LB in artificial cycles when using a combination of oral dydrogesterone and vaginal progesterone for luteal phase support. In addition, prospective, randomized, controlled, blinded trials are merited to determine the optimal dosing regimen for oral dydrogesterone in in AC-FET for LPS.

Sign in / Sign up

Export Citation Format

Share Document