The Impact of the Time Interval Between Cycles on Pregnancy Outcome of Ovulation Induction Cycle Intrauterine Artificial Insemination

Author(s):  
shuai zhang ◽  
Ming-lian Zhou ◽  
Han-han Tang ◽  
Hui-juan Guan

Abstract ObjectiveThe objective of this study was to estimate whether the time interval between two intrauterine inseminations (IUI) treatments needs to be extended by one menstrual cycle or more in patients undergoing successive cycles of ovulation stimulation, and whether this will have an impact on the clinical pregnancy rate (CPR).Study DesignRetrospective cohort study.Study siteThe study site was the reproductive medicine center of a teaching hospital.Patient(s)The subjects were women and their husbands who received two or more intrauterine insemination in our reproductive medicine center due to mild infertility in the period from January 2017 to December 2019. Patients were divided into 2 groups according to the number of days between the last menstrual day(LMD)and the previous IUI operation day(POD), continuous group (the time from the LMD to POD ≤ 34 days) and delayed group (the time from the LMD to POD ≥ 35 days). We excluded cycles with intervals of more than 180 days.In order to avoid the inclusion of multiple repeat cycles for the same couple, only the first two cycles of IUI treatment in the same couple were allowed to be included in this study. That is, when they failed the first IUI cycle, they were given a second IUI treatment.Intervention(s)No intervention.Main Outcome Measure(s)A total of 550 cycles met the inclusion criteria, and 374 (68.0%) cycles met the inclusion criteria for the continuous group,the remaining 176 (32.0%) cycles with at least one or more menstruations between two IUI cycles were included in the delayed group.The primary outcome measure was clinical pregnancy rate (CPR), with secondary outcomes including abortion rate. Differences in clinical pregnancy rate (CPR)、abortion rate were compared between the two groups.ResultThere was no significant difference between the continuous group and the delayed group in female age, male age, infertility duration, infertility type, female BMI, endometrial classification, endometrial thickness, semen volume before treatment, sperm density before treatment, percentage of forward motile sperm before treatment, sperm density after treatment, and percentage of forward motile sperm after treatment. There were no statistical differences between the delayed group vs continuous group regarding the clinical pregnancy rate (20.5 % vs 21.9 %) and abortion rate (27.8% vs 22.0%)(P>0.05). The above factors were included for binary logistic regression analysis. It was found that the increase of endometrial thickness promoted the clinical pregnancy rate, which was statistically significant (OR=1.205, 95% CI 1.05-1.384,P=0.008). Compared with primary infertility, secondary infertility can promote the improvement of clinical pregnancy rate, which is statistically significant (OR=2.637,95%CI 1.313-5.298,P=0.006). The effect of time interval between IUI on clinical pregnancy was not statistically significant (OR=1.007,95% CI 0.513-1.974,P=0.985).ConclusionsOverall, prolonging the interval between two IUI did not significantly improve pregnancy outcomes. Unless there are clear clinical indications, it is not necessary to deliberately prolong the interval between two treatments.

2021 ◽  
Author(s):  
shuai zhang ◽  
minglian zhou ◽  
Hanhan Tang ◽  
Huijuan Guan ◽  
Huaiyun Tang

Abstract Objective: The objective of this study was to estimate whether the time interval between two intrauterine inseminations (IUI) treatments needs to be extended by one menstrual cycle or more, and whether this will have an impact on the clinical pregnancy rate (CPR).Study Design: Retrospective cohort study.Study site: The study site was the reproductive medicine center of a teaching hospital.Patient(s): The subjects were women and their husbands who received two or more intrauterine insemination in our reproductive medicine center due to mild infertility in the period from January 2014 to December 2020. Patients were divided into 2 groups according to the number of days between the last menstrual day(LMD)and the previous IUI operation day(POD), continuous group (the time from the LMD to POD ≤ 34 days) and delayed group (the time from the LMD to POD ≥ 35 days). If the previous cycle was a pregnancy or abortion cycle, the next cycle immediately adjacent to it was defined as a new cycle, and the days between the two cycles were not included in the study.Intervention(s):No intervention.Main Outcome Measure(s): A total of 1491 cycles were finally included in the study.990 cycles followed by the second IUI cycle after the previous failure,501 cycles at least one menstrual cycle was separated between two IUI treatments. The primary outcome measure was clinical pregnancy rate (CPR), with secondary outcomes including abortion rate and live birth rate. Differences in clinical pregnancy rate (CPR)、abortion rate and live birth rate were compared between the two groups.Result: No significant differences with regard to baseline demographic and the number of treatment cycles, the duration of infertility, the type of infertility, the mode of treatment, and the cause of infertility were observed between the two groups.There were no statistical differences between the delayed group vs continuous group regarding the clinical pregnancy rate(15.0% vs 13.7%), live birth rate(78.7% vs 74.3%), and abortion rate(17.3% vs 18.4%)(P>0.05).The above factors were included for binary logistic regression analysis. The observed difference in clinical pregnancy rate between the groups was not statistically significant after adjustment(OR = 1.101,95%CI 0.807-1.499, P=0.546).The all cycles were divided into four groups based on female age. results showed that when the female's age was ≤ 25 years old, the pregnancy rate in the continuous group was 16.5%, which was significantly higher than that in the delayed group by 5.8% (difference 0.107, 95% CI 0.016-0.198, P = 0.055), approached, but did not reach, statistical significance. When the female was 30-35 years old, the pregnancy rate in the delayed group was 19.4%, which was significantly higher than 10.9% in the continuous group (difference 0.085, 95% CI 0.016-0.154, P = 0.011). The difference between the two groups was statistically significant. The all cycles were divided into three groups based on years of infertility. Our results show that when the number of years of infertility was≤2 years, the clinical pregnancy rate was 20.7% in the delayed group and 12.5% in the continuous group (difference 0.107, 95% CI 0.150-0.014, P = 0.013), statistical significance was maintained. Based on the number of treatment cycles, it is divided into 2 cycles, 3 cycles, and≥4 cycles. The results showed that when≥4 cycles, the pregnancy rate in the continuous group were 19.4%, which was significantly higher than 6.1% in the delayed group (difference 0.133, 95% CI 0.246-0.020, P = 0.038). Statistical significance was maintained at P < 0.05.Conclusions: Overall, prolonging the interval between two IUI did not significantly improve pregnancy outcomes. Yet, for different age stages, duration of infertility, and the number of treatment cycles, we suggest that more flexible treatment strategies can be tried to improve the clinical pregnancy rate.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
P C Jindal ◽  
M Singh

Abstract Study question Does GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to GCSF by the subcutaneous route, in IVF-ICSI Cycles? Summary answer Yes, GCSF by intrauterine route leads to better result in the treatment of thin endometrium as compared to subcutaneous-GCSF, in ART Cycles? What is known already GCSF, is a member of the colony stimulating factor family of cytokines and growth factors. GCSF receptors are expressed in high concentration on dominant follicle, particularly at preovulatory stage.The endometrium also shows an increased expression of these receptors. GCSF concentration rises in the follicular fluid at the same time. Serum levels of GCSF are found to be in direct correlation with levels of GCSF in follicular fluid. Serum levels increase progressively from the day the embryo-transfer to the day of implantation. GCSF has been found to be beneficial in patients with thin endometrium and recurrent implantation failure. Study design, size, duration This was a RCT conducted between 2018–2019. 30 patients with thin endometrium were enrolled in each group. In either group, GCSF was given if endometrium was less than 7mm on day 14, maximum of two doses were administered. Patients undergoing frozen embryo transfer were recruited in the study, after meeting the inclusion and exclusion criteria. Primary outcome measured was increase in endometrium thickness and the secondary outcome was the clinical pregnancy rate and abortion-rate. Participants/materials, setting, methods 60 patients with thin endometrium were randomly divided into two groups. Group A: Inj. GCSF (300 mcg/1 ml) subcutaneously on Day 14 onwards alternate days for two doses. Group B: Inj. GCSF (300 mcg/1 ml) instilled slowly into the uterine cavity using an intrauterine insemination (IUI) catheter under USG guidance. Endometrial thickness was assessed after 48 h. If endometrial thickness was found to be &lt; 7 mm, a second infusion of GCSF was carried out. Main results and the role of chance In the subcutaneous group (group-A) the mean endometrial thickness before GCSF injection was 5.8 ± 0.6 mm and, after injection it increased to 6.9 ± 0.4 mm. Similarly, in the intrauterine group (group-B) the mean endometrial thickness before GCSF was 5.9 ± 0.7 which increased to a mean of 7.9 ± 0.5 after GCSF instillation. The difference between endometrial thickness before and after intrauterine infusion of GCSF was more than that in the subcutaneous group. In group-A, 08 patients conceived out of 30 patients ( clinical pregnancy rate 26.6%) and in group B 11 conceived out of 30 patients in whom GCSF was instilled intrauterine (pregnancy rate 36.6%). Thus, there was a difference in the clinical pregnancy rate in the two groups, the intrauterine group yielding a higher clinical pregnancy rate, but it was not statistically significant. Because of the thin endometrium, we found an abortion rate of 25% (2/8) in the subcutaneous-GCSF group, and an abortion rate of 18% (2/11) in the intrauterine GCSF group. Limitations, reasons for caution There are few potential limitations because of the small sample size. Confounders such as obesity, smoking and alcohol intake, presence of adenomyosis and endometriosis, were not taken into consideration. Though prevalence of obesity is usually low in Indian women. Habits of smoking and alcohol are exceedingly uncommon in Indian women. Wider implications of the findings: Use of GCSF plays an important role in management of patients of thin endometrium undergoing embryo transfer. It is an easily available and economical preparation in developing countries and the intrauterine instillation of GCSF can be easily practiced in an ART unit with good results in resistant thin endometrium patients. Trial registration number Not applicable


2021 ◽  
Vol 12 ◽  
Author(s):  
Danjun Li ◽  
Shuzin Khor ◽  
Jialyu Huang ◽  
Qiuju Chen ◽  
Qifeng Lyu ◽  
...  

ObjectiveTo evaluate the clinical effect of mild stimulation with letrozole on pregnancy outcomes in ovulatory women undergoing frozen embryo transfer (FET) compared to natural cycle.DesignRetrospective observational study.SettingTertiary care academic medical center.PopulationA total of 6,874 infertile women with regular menstrual cycles (21-35 days) met the criteria for this study in the period from 2013 to 2020.MethodsAll patients who were prepared for and underwent FET were divided into two groups: a modified natural cycle (NC) group (n=3,958) and a letrozole cycle group (n=2,916).Main Outcome MeasuresThe primary outcome of the study was clinical pregnancy rate. Secondary outcome measures were endometrial thickness, rates of implantation, positive HCG test, live birth, early miscarriage and ectopic pregnancy.ResultsThe clinical pregnancy rate was not statistically different between the modified NC-FET group and the letrozole-FFT group before (crude OR 0.99, 95% CI 0.90-1.09, P=0.902&gt;0.05) and after propensity score matching (PSM) (crude OR 1.01, 95% CI 0.91-1.12, P=0.870&gt;0.05). After multivariable logistic regression analysis, the clinical pregnancy rate remained insignificant before (adjusted OR 1.00, 95% CI 0.91-1.10, P=0.979&gt;0.05) and after matching (adjusted OR 1.00, 95% CI 0.89-1.11, P=0.936&gt;0.05), respectively. Similarly, in the crude and adjusted analysis, the positive HCG test, implantation, live birth and early miscarriage rates were also comparable in the letrozole-FFT group and modified NC-FET group before and after matching. Furthermore, the endometrial thickness of letrozole-FFT group was similar to that of modified NC-FET group with adjusted analysis.ConclusionOur observation suggests that mild stimulation with letrozole could produce similar pregnancy outcomes in ovulatory patients who undergo FET when compared with a natural cycle.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Abalı ◽  
F K Boynukalın ◽  
M Gültomruk ◽  
Z Yarkiner ◽  
M Bahçeci

Abstract Study question Does the outcome of the first euploid frozen-thawed blastocyst embryo transfer affect the subsequent euploid FBT originating from the same cohort of oocytes? Summary answer The clinical pregnancy rate and ongoing pregnancy rate of the subsequent FBT are higher if a clinical pregnancy was attained in the first euploid FBT. What is known already Numerous factors including patient, cycle and embryological characteristics affect the outcome of an IVF treatment cycle. There is no data available whether the outcome of euploid FBT has an impact on the outcome of the subsequent euploid FBT of embryos originating from the same cohort of retrieved oocytes. Study design, size, duration The study enrolled cycles preimplantation genetic test for aneuploidy (PGT-A) performed between January 2016 and July 2019 at the Bahceci Fulya IVF Center. A total of 1051 patients with single euploid FBT were evaluated and resulted live birth (n = 589, live birth rate (LBR): 56%(589/1051)), miscarriage (n = 100, miscarriage rate (MR): 14.5% (100/689)) and no clinical pregnancy (n = 362, 34,4%, (362/1051)). 159 FBT after the first single euploid FBT originating from the same cohort of oocytes were analyzed. Participants/materials, setting, methods Second euploid FBT cycle after first FBT with a clinical pregnancy were compared to frozen-thawed cycles after a without a pregnancy. Logistic regression analysis was utilized to adjust for potential confounders including female age, body mass index, embryo quality, day of embryo frozen, number previous failed attempt, number of previous miscarriage, endometrial thickness, outcome of the first euploid FBT. Main results and the role of chance The pregnancy outcome from the first euploid FBT in the study group was resulted live birth (25.1%, (40/159)), miscarriage (15.7%, (25/159)) and no clinical pregnancy (59.1%, (94/159). The pregnancy outcome of the subsequent euploid embryo transfer from the same oocyte cohort was clinical pregnancy rate (CPR): (67.3%, (107/159) ongoing pregnancy rate (OPR) (52.2% (83/159) and MR (22.4%, (24/107)). The CPR in the subsequent euploid FBT was 80% (52/65) among patients who achieved a clinical pregnancy in the first euploid FBT and 58.5% (55/94) of those who did not (p = 0.0045). The OPR in the subsequent euploid FBT was 64.6% (42/65) among patients who achieved a clinical pregnancy in first euploid FBT and 43.6% (41/94) of those who did not (p = 0.009). On a multivariate regression analysis, clinical pregnancy in the first euploid FBT was a significant independent predictor for a pregnancy in the subsequent FBT transfer (p = 0.003). Limitations, reasons for caution The limitation of the study is in the retrospective nature of the study. As the PGT-A strategy significantly decreases number of transferable embryos, the sample size of the study is limited. Wider implications of the findings: Identifying predictive factors for the success of euploid FBT is important. These can help physicians while counseling patients regarding the outcome of the previous euploid FBT. Trial registration number NA


2020 ◽  
Author(s):  
Shahintaj Aramesh ◽  
Maryam Azizi Kutenaee ◽  
Fataneh Najafi ◽  
Parvin Ghafari ◽  
seyed abdolvahab taghavi

Abstract Background The cause of infertility has not been found in unexplained infertile patients,, and perhaps one of the possible reasons is impairment of fetal implantation, as well as the multiple role of GCSF in improving implantation and quality of blastocyst. Therefore, the aim of this study was to investigate the role of GCSF in the pregnancy rate of patients undergoing IUI.Methods The patients with unexplained infertility were divided into two groups: one group was received GCSF in their IUI cycle and the other group had the routine IUI. Both groups were stimulated by letrozole, metformin, and monotropin during the cycle. When at least one follicle was greater than 18 mm, 5000 IU hCG intramuscularly was administered for ovulation induction and IUI was performed 34–36 hours later. In intervention group, 300 ug GCSF subcutaneously administrated in two days after IUI. Biochemical pregnancy rate was evaluated two weeks after IUI and clinical pregnancy rate was identified by the presence of a gestational sac on ultrasonography 8 weeks after IUI.Results There was no significant difference in demographic and clinical characteristics between the two groups. The chemical pregnancy rate(16.3% vs 12.2%) and the clinical pregnancy rates (16.3% vs 8.3%) were improved in patients receiving GCSF compared to controls, but these differences was not significant (P = 0.56) and (P = 0.21).Conclusion Systemic administration of a single dose of 300 µg GCSF subcutaneously two days after IUI may slightly improve clinical pregnancy rate in patients with unexplained infertility. Nevertheless, our findings do not support routine use of G-CSF in unexplained infertility women with normal endometrial thickness.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jie Zhang ◽  
Yi-Fei Sun ◽  
Yue-Ming Xu ◽  
Bao-jun Shi ◽  
Yan Han ◽  
...  

ObjectiveTo investigate the factors that influence luteal phase short-acting gonadotropin-releasing hormone agonist (GnRH-a) long protocol and GnRH-antagonist (GnRH-ant) protocol on pregnancy outcome and quantify the influence. About the statistical analysis, it is not correct for the number of gravidities.MethodsInfertile patients (n = 4,631) with fresh in-vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) and embryo transfer were divided into GnRH-a long protocol (n =3,104) and GnRH-ant (n =1,527) protocol groups and subgroups G1 (EMT ≤7mm), G2 (7 mm &lt;EMT ≤10 mm), and G3 (EMT &gt;10 mm) according to EMT on the trigger day. The data were analyzed.ResultsThe GnRH-ant and the GnRH-a long protocols had comparable clinical outcomes in the clinical pregnancy, live birth, and miscarriage rate after propensity score matching. In the medium endometrial thickness of 7–10 mm, the clinical pregnancy rate (61.81 vs 55.58%, P &lt; 0.05) and miscarriage rate (19.43 vs 12.83%, P &lt; 0.05) of the GnRH-ant regime were significantly higher than those of the GnRH-a regime. The EMT threshold for clinical pregnancy rate in the GnRH-ant group was 12 mm, with the maximal clinical pregnancy rate of less than 75% and the maximal live birth rate of 70%. In the GnRH-a long protocol, the optimal range of EMT was &gt;10 mm for the clinical pregnancy rate and &gt;9.5 mm for the live birth rate for favorable clinical outcomes, and the clinical pregnancy and live birth rates increased linearly with increase of EMT. In the GnRH-ant protocol, the EMT thresholds were 9–6 mm for the clinical pregnancy rate and 9.5–15.5 mm for the live birth rate.ConclusionsThe GnRH-ant protocol has better clinical pregnancy outcomes when the endometrial thickness is in the medium thickness range of 7–10 mm. The optimal threshold interval for better clinical pregnancy outcomes of the GnRH-ant protocol is significantly narrower than that of the GnRH-a protocol. When the endometrial thickness exceeds 12 mm, the clinical pregnancy rate and live birth rate of the GnRH-ant protocol show a significant downward trend, probably indicating some negative effects of GnRH-ant on the endometrial receptivity to cause a decrease of the clinical pregnancy rate and live birth rate if the endometrial thickness exceeds 12 mm.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaxin Zhang ◽  
Linli Hu ◽  
Zhiqin Bu ◽  
Yingpu Sun

BackgroundSome studies have demonstrated that adenomyosis patients can achieve a comparable pregnancy outcome with women with normal uteruses, while there is no unanimous conclusion at present.MethodWe recruited 65 adenomyosis patients and 260 frequency-matched control women with endometriosis at a ratio of 1:4 according to age. Clinical pregnancy rate, spontaneous abortion rate, and live birth rate were compared between these two groups after controlling other factors.ResultsCompared with endometriosis patients, adenomyosis patients had a higher antral follicle count (AFC) (12.71 vs 11.65, P=0.027). Though the two groups had the same number of embryos transferred, adenomyosis patients had an obviously declined implantation rate (31.91% vs 46.74%, P=0.005), clinical pregnancy rate (47.06% vs 64.42%, P=0.028), live birth rate (31.37% vs 54.81%, P=0.004), and significantly increased spontaneous abortion rate (33.33% vs 13.43%, P=0.034). Multivariate logistic regression analysis showed that adenomyosis had adverse influences on pregnancy outcome when age and the number of embryo transfers were controlled (adjusted OR=0.361, P=0.003).ConclusionEven after being matched with age, adenomyosis still had adverse influences on the pregnancy outcome of IVF in patients undergoing the long protocol.


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