scholarly journals Only extremely high peak serum estradiol adversely affects endometrial receptivity in IVF treatment

2019 ◽  
Author(s):  
Jianyuan Song ◽  
Tingting Liao ◽  
Liu Jiang ◽  
Houming Su ◽  
Licheng Ji ◽  
...  

Abstract Purpose To explore the effect of different concentrations of peak serum estradiol levels on endometrial receptivity quantitatively. Methods In our reproductive medicine center, two best quality of day 3 (D3) embryos were transferred or frozen according to E 2 and progesterone levels on the day of human chorionic gonadotropin (hCG) administration and the number of oocytes retrieved. The remaining embryos were cultured to blastocyst stage and frozen. The patients were then categorized into three groups. The patients with frozen-thawed D3 embryo transfer in artificial cycles without blastocyst frozen served as group 1, those with fresh D3 embryo transfer without blastocyst frozen as group 2, and those with fresh D3 embryo transfer with blastocyst frozen as group 3. Each group was further stratified into 4 sub-groups according to E 2 levels on the day of hCG administration. Clinical pregnancy rate, implantation rate and abortion rate of frozen-thawed and fresh D3 embryo transfer were compared among the three groups in the same stratified E 2 levels. Results For E 2 <7,000 pg/mL, group 1 and group 2 had similar clinical pregnancy rate and implantation rate. But for E 2 ≥7,000 pg/mL, the clinical pregnancy rate in group 1 was significantly higher than in group 2 (p<0.05). For E 2 <7,000 pg/mL, pregnancy rate and implantation rate in group 1 were significantly lower than those in group 3 (P<0.05). But for E 2 ≥7,000 pg/mL, the pregnancy rate in group 1 was significantly higher than in group 3 (P<0.05). There was no significant difference in the abortion rate between group 1 and group 2, or between group 1 and group 3. Conclusions High serum E 2 concentration does not impair implantation and pregnancy rates unless exceeding a certain limit (e.g. 7,000 pg/mL) on the day of hCG administration. Since peak E 2 level was related to OHSS and adverse pregnancy outcomes, further study is needed to set a threshold peak E 2 level for fresh embryo transfer.

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


2016 ◽  
Vol 28 (2) ◽  
pp. 250
Author(s):  
R. C. Fry ◽  
R. Mapletroft ◽  
G. A. Bo ◽  
M. M. Izzo ◽  
M. A. Humphris

The aim of this experiment was to compare a single FSH/eCG, or double FSH-0.5% hyaluronan/eCG injection protocol with a multiple FSH/eCG injection protocol on the superovulatory response and embryo production in sheep. In addition, the effect of vitrification of these embryos on the pregnancy rate following embryo transfer was evaluated. Eighty Dohne Merino ewes received an 8-day CIDR-S device (0.33 g P4; Zoetis, Florham Park, NJ, USA) plus 10 mg of FSH i.m. (Folltropin-V; Vetoquinol, Lavaltrie, QC, Canada) and 400 IU of eCG i.m. (Pregnecol; Vetoquinol) in 3 treatment groups. Group 1 (n = 21) received a single 10-mg FSH injection in saline and 400 IU of eCG in saline 2.5 days before CIDR withdrawal. Group 2 (n = 23) received 6.7 mg of FSH in hyaluronan (MAP-5, 50 mg; Vetoquinol) and 400 IU of eCG in saline 2.5 days before CIDR withdrawal and 3.3 mg of FSH in hyaluronan 0.5 days before CIDR withdrawal. Group 3 (n = 36) received 7 injections (am, pm) of FSH in saline (2.5, 2.0, 1.5, 1.5, 1.0, 1.0, 0.5 mg) starting 2.5 days before CIDR withdrawal and 400 IU of eCG in saline at the first injection. Ewes were inseminated with semen collected from 1 of 5 rams at 36 to 40 h after CIDR withdrawal. Donor ewes were slaughtered 6 days after AI (Day 0), CL were counted and ova/embryos were collected. Viable embryos were transferred in singles into Day 6 synchronised recipients as either fresh (n = 128) or following vitrification/thawing using the CVM (CryoLogic, Blackburn, VIC, Australia; n = 97; Fry et al. 2005 Reprod. Fertil. Dev. 17, 243). Pregnancy was diagnosed by ultrasound scanning on Day 45. Data for CL and transferable embryo were analysed by the Kruskall-Wallis test and differences between groups determined by the Dunn test. Data for pregnancy rates was compared by chi-squared analysis. The mean number of CL in Groups 2 and 3 were both significantly higher than that in Group 1 (12.3 and 12.0 v. 8.5; P < 0.05). Similarly, the total number of embryos/ova recovered in Groups 2 and 3 were significantly higher than for Group 1 (8.3 and 7.0 v. 5.0; P < 0.05). Group 3 produced more viable embryos than either Group 2 or Group 1 (4.6 v. 2.7 and 2.1; P < 0.05); however, data were skewed by the extensive use of semen from one ram in Group 2 that had a low fertilization rate (28%). The transfer of vitrified/thawed embryos resulted a nonsignificant (P > 0.05) 10% decrease in pregnancy rate compared with fresh embryos (66% v. 76%). In conclusion, the administration of the sustained release FSH-MAP-5 in a 2-injection protocol in sheep was as effective as a multiple FSH injection protocol in inducing an ovarian response but more research is required to elucidate the effect of FSH-MAP-5 on embryo quality. The successful vitrification of sheep embryos provides a promising technique for the storage and transport of embryos in large-scale sheep embryo transfer programs.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
T Huong ◽  
A Ph. Th. Tú ◽  
L H Mai ◽  
N Doã. Thảo ◽  
C A Mạnh

Abstract Study question Is that essential for prolonged culture of thawed blastocysts in order to be fully re-expanded before transferring? Summary answer Ongoing pregnancy rates decreased in blastocysts that not fully re-expanded after thawing. What is known already: The thaw survival of blastocysts is examined based on morphology of inner cell mass (ICM) and trophectoderm (TE). However, thawed blastocysts experience multiple changes in morphology and might be collapse after thawing due to the presence of blastocoel cavity. It is then difficult to evaluate blastocyst quality. Therefore, the blastocyst re-expansion is considered as a criteria to assess quickly the competent embryos. It also reflects the status energy metabolism from high quality embryo. After all, there are still some controversial opinions about the influence of re-expansion status after thawing. Study design, size, duration This was a retrospective study based on data collected between October 2019 and December 2020. A total 528 thawed blastocysts which were divided into two groups according to the post-thaw reexpansion status: fully re-expanded blastocysts (n = 416), partial or no re-expanded blastocysts (n = 112). The re-expansion status of blastocyst was assess prior to loading on the catheter by senior embryologists. Participants/materials, setting, methods Primary outcome is ongoing pregnancy. Only frozen single D5 transfer cycles were included. We excluded the frozen sperm/oocytes/embryos donation cycles, missing data, non-intact embryos after thawing. Statistical analyses were performed with T or chi-squared tests. Multivariable regression analysis was performed adjusting for the following confounding factors: age, BMI, embryo quality, re-expansion status, biopsied blastocyst. Main results and the role of chance Female age, BMI, number of previous cycles, endometrial thickness, positive HCG results, clinical pregnancy rate were comparable among patients within two groups. The rate of ongoing pregnancy rate in group 1 was significant higher compared with group 2 (51 vs 40.2, p &lt; 0.05). The number of good quality blastocyst transferred in group 1 was higher than in group 2 (p &lt; 0.001). However, under the same embryo quality, there were no difference between clinical pregnancy rate and ongoing pregnancy rate between two groups. When logistic regression were performed: only embryo quality, but not the re-expansion status, was noted to be an independent predictor of ongoing pregnancy (OR = 3.53;95% CI; 1.734–7.184;p=0.001). Limitations, reasons for caution The main limitation of the study is its retrospective design. Wider implications of the findings: Clinical outcomes are comparable between re-expanded blastocyst and partial or no re-expanded blastocysts, although ongoing pregnancy can be improved when embryos are fully expanded. As expected, blastocysts quality has the most important impact on ongoing pregnancy rate. Trial registration number Not applicable


Lupus ◽  
2021 ◽  
pp. 096120332110558
Author(s):  
Rui Gao ◽  
Wei Deng ◽  
Cheng Meng ◽  
Kemin Cheng ◽  
Xun Zeng ◽  
...  

Background The influence of anti-nuclear antibody (ANA) on induced ovulation was controversial, and the effect of prednisone plus hydroxychloroquine (HCQ) treatment on frozen embryo transfer outcomes of in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) for ANA-positive women was unclear. Methods Fifty ANA-positive women and one-hundred ANA-negative women matched for age and anti-Mullerian hormone (AMH) were included from a Reproductive Medical Central of a University Hospital. Sixty-one oocytes pick-up (OPU) cycles in ANA+ group and one-hundred OPU cycles in ANA− group were compared; 30 frozen embryo transfer cycles without treatment and 66 with prednisone plus HCQ treatment among ANA-positive women were compared. Results There was no statistical difference in number of retrieved oocytes (13.66 ± 7.71 vs 13.72 ± 7.23, p = .445), available embryos (5.23 ± 3.37 vs 5.47 ± 3.26, p = .347), high-quality embryos (3.64 ± 3.25 vs 3.70 ± 3.52, p = .832), and proportion of high-quality embryos (26.5% vs. 26.7%, p = .940). Biochemical pregnancy rate (33.3% vs. 68.2%, p < .05), clinical pregnancy rate (20.0% vs. 50.1%, p < .05), and implantation rate (5.6% vs. 31.8%, p < .05) were lower, and pregnancy loss rate (83.3% vs. 23.1%, p < .05) was higher in patients with treatment than no treatment. Conclusion The influence of ANA on number of retrieved oocytes, available embryos, high-quality embryos, and proration of high-quality embryos was not found. The treatment of prednisone plus HCQ may improve implantation rate, biochemical pregnancy rate, and clinical pregnancy rate, and reduce pregnancy loss rate in frozen embryo transfer outcomes for ANA-positive women.


2020 ◽  
Author(s):  
Yuan Liu ◽  
Yixia Yang ◽  
Xinting Zhou ◽  
Yanmei Hu ◽  
Yu Wu

Abstract Background: Previous studies have demonstrated that newborns from fresh embryo transfer are with higher risk of small for gestation (SGA) rate than those from frozen-thawed embryo transfer (FET). It is suggested that supraphysiologic serum estradiol in controlled ovarian stimulation (COS)is one of reasons. Out study aims to investigate whether exogenous estradiol delivered regimens have an impact on live birth rate and singleton birthweight in hormone replacement (HRT)-FET cycles.Methods:This retrospective study involved patients undergoing their first FET with HRT endometrium preparation followed by two cleavage-staged embryos transfer, comparing orally and vaginal estradiol tablets (OVE) group versus oral estradiol tablets (OE) group from January 2015 to December 2018 at our center. A total of 792 patients fulfilled the criteria, including 282 live birth singletons. Live birth was the primary outcome. Secondary outcome included clinical pregnancy rate, singleton birthweight, large for gestational age (LGA) rate, SGA rate, preterm delivery rate. Results:Patients in OVE group achieved higher serum estradiol level with more days of estradiol treatment. No difference in live birth (Adjusted OR 1.327; 95%CI 0.982, 1.794, p=0.066) and clinical pregnancy rate (Adjusted OR 1.278; 95%CI 0.937, 1.743, p=0.121) was found between OVE and OE groups. Estradiol route did not affect birth weight (β=-30.962, SE=68.723, p=0.653), the odds of LGA (Adjusted OR 1.165; 95%CI 0.545, 2.490, p=0.694), the odds of SGA (Adjusted OR 0.569; 95%CI 0.096, 3.369, p=0.535) or the preterm delivery rate (Adjusted OR 0.969; 95%CI 0.292, 3.214, p=0.959).Conclusion:Estrogen orally and vaginally together did not have an impact on clinical outcomes and singleton birthweight compared to estrogen orally taken, but was accompanied with relative higher serum E2 level and potential maternal undesirable risks.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Han-Chih Hsieh ◽  
Chun-I Lee ◽  
En-Yu Lai ◽  
Jia-Ying Su ◽  
Yi-Ting Huang ◽  
...  

Abstract Background For women undergoing in vitro fertilization (IVF), the clinical benefit of embryo transfer at the blastocyst stage (Day 5) versus cleavage stage (Day 3) remains controversial. The purpose of this study is to compare the implantation rate, clinical pregnancy rate and odds of live birth of Day 3 and Day 5 embryo transfer, and more importantly, to address the issue that patients were chosen to receive either transfer protocol due to their underlying clinical characteristics, i.e., confounding by indication. Methods We conducted a retrospective cohort study of 9,090 IVF cycles collected by Lee Women’s Hospital in Taichung, Taiwan from 1998 to 2014. We utilized the method of propensity score matching to mimic a randomized controlled trial (RCT) where each patient with Day 5 transfer was matched by another patient with Day 3 transfer with respect to other clinical characteristics. Implantation rate, clinical pregnancy rate, and odds of live birth were compared for women underwent Day 5 transfer and Day 3 transfer to estimate the causal effects. We further investigated the causal effects in subgroups by stratifying age and anti-Mullerian hormone (AMH). Results Our analyses uncovered an evidence of a significant difference in implantation rate (p=0.04) favoring Day 5 transfer, and showed that Day 3 and Day 5 transfers made no difference in both odds of live birth (p=0.27) and clinical pregnancy rate (p=0.11). With the increase of gestational age, the trend toward non-significance of embryo transfer day in our result appeared to be consistent for subgroups stratified by age and AMH, while all analyses stratified by age and AMH were not statistically significant. Conclusions We conclude that for women without strong indications for Day 3 or Day 5 transfer, there is a small significant difference in implantation rate in favor of Day 5 transfer. However, the two protocols have indistinguishable outcomes on odds of live birth and clinical pregnancy rate.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
K D Nayar ◽  
S Gupta ◽  
R Bhattacharya ◽  
P Mehra ◽  
J Mishra ◽  
...  

Abstract Study question To compare the efficacy of transdermal testosterone with placebo (lubricant gel) in improving IVF outcomes using GnRH antagonist protocol in POSEIDON group 3 and 4 patients. Summary answer Patients receiving pre-treatment with testosterone gel had higher mean number of oocytes retrieved and grade A embryos as compared to the patients receiving lubricant gel. What is known already Diminished ovarian reserve (DOR) is associated with suboptimal ovarian response, higher cycle cancellation rate and lower clinical pregnancy rate following IVF cycles. Various treatment regimens have been devised for management of such patients and use of adjuvants in the form of oral or transdermal androgen is one of them. Androgens improves follicular response to gonadotropin stimulation as well as increase FSH receptor expression in granulosa cells, in turn leading to better oocyte yield and pregnancy rate. Aim was to compare the effect of transdermal testosterone gel with placebo gel on ART outcome in DOR patients (POSEIDON Group 3 and 4). Study design, size, duration A prospective, randomised controlled trial was carried out from 1st September 2019 to 31st October 2020 at a tertiary infertility centre in India. 50 patients fulfilling the criteria of Group 3 and Group 4 of POSEIDON classification were included in the study. Patients with endocrine disorders (thyroid, prolactin), endometrioma, history of surgery on the ovaries, sensitivity to testosterone gel, male factor infertility and deranged liver and renal function tests were excluded. Participants/materials, setting, methods Enrolled patients were randomised into two groups of 25 patients each, one group was pretreated (TTG group) with transdermal testosterone gel, 12.5 mg/day from day 6th of previous cycle to day 2nd of stimulation cycle while patients in other group took lubricant gel for the same duration before stimulation with GnRH antagonist fixed protocol followed by fresh Day 3 transfer. Main results and the role of chance The baseline characteristics of the two groups were comparable. The primary outcome measures were the number of oocytes retrieved and number of grade A embryos formed (according to Istanbul consensus). The secondary outcome measures were implantation rate, clinical pregnancy rate, miscarriage rate and ongoing pregnancy rate. The mean number of oocytes retrieved in TTG group was 5±1.02 which was significantly higher than placebo group–3.5±1.2, (p &lt; 0.001). The mean number of Grade A embryos were also significantly higher (4.78±0.54 vs 3.00±0.23, p &lt; 0.001) in TTG group. The TTG group had higher implantation rate (28% vs 20%, p = 0.49), clinical pregnancy rate (32% vs 18%, p = 0.41), ongoing pregnancy rate (32% vs 16%, p = 0.38) and lower miscarriage rate (0% vs 20%, p = 0.38), however, these differences were not statistically significant. Limitations, reasons for caution The study was done at a single centre with small sample size, replication with more subjects and in different centers is needed. Wider implications of the findings: Pre-treatment with testosterone gel in DOR patients improves ovarian response to stimulation and results in higher number of oocytes retrieved and good quality embryos resulting in improved clinical pregnancy rates. Transdermal testosterone is advantageous because of better bioavailability, easy application, patient friendly and less adverse effects. Trial registration number MCDH/2019/54


2020 ◽  
Author(s):  
Mingmei Lin ◽  
Zi-Ru Niu ◽  
Rong Li

BACKGROUND It is well known that assisted reproduction technology (ART) is currently an effective method for treating infertility. But it is currently unknown whether the patients with fever after control ovulation during egg retrieval could increase risk of pelvic infection or not, and fever itself may be affect oocyte or embryo quantity and quality, thus with poor pregnancy outcomes? But if the oocyte retrieval was cancelled cause of fever, the risk of severe ovulation complications might increase, such as ovarian hyper-stimulation syndrome, thrombus and ovarian pedicle torsion. OBJECTIVE The goal of this study was to analysis the outcomes of the patients with fever during oocyte retrieval after the first frozen-thawed embryo transfer cycle. METHODS This is a 1:3 retrospective paired study matched for age. In this study, 58 infertility patients (Group 1) had fever during the control ovulation and the time of the oocyte retrieval within 72 hours, they undertook ovum pick up and whole embryo freezing (“freeze-all” strategy). The control controls (Group 2) are174 patients matched for age with whole embryo freezing for other reasons. The baseline characteristic, clinical data of ovarian stimulation and the outcomes, such as the clinical pregnancy rate, early miscarriage rate, ectopic pregnancy rate and ongoing clinical pregnancy rate were compared between the two groups. RESULTS There were 58 patients were enrolled in the Group 1, and matched with 174 patients for the Group 2. All the patients had no pelvic inflammatory disease after oocyte retrieval. The basic characteristics of patients refers to age, BMI, nulliparity, basal FSH, basal LH, basal E2 and infertility type (primary or secondary) were with no significantly difference. But the AMH lever (4.2 versus 2.2, P<0.001) were higher and the infertility time (3 versus 2, P=0.035) was longer in the control group. The number of oocytes retrieved and fertilization rate were lower in the group (P< 0.001), but the ovarian stimulation protocol, the usage of Gn both time and dose, the ICSI rate, the 2PN rate, the number of available embryos (D3 and D5), the endometrial thickness, the number of embryo transfer and the type of luteal support supplementation were similar between the two groups. Regarding pregnancy outcomes,the implantation rate, clinical pregnancy rate, early spontaneous rate, ectopic pregnancy rate and ongoing pregnancy rate all were with no significantly difference. CONCLUSIONS The patients with fever during control ovulation and the oocyte retrieval got similar outcomes compared with those with no fever patients when taken the whole embryos freezing. Fever had almost no effect on the quality of embryo and endometrium. Moreover, the oocyte retrieved is relatively safe and reliable under strict disinfection and taken oral antibiotics for prevention infection.


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