Can U Still Get Pregnant Again With a 5 Mm Endometrium Thickness
Reprod Biol Endocrinol. 2014; 12: 96.
Endometrial thickness affects the result of in vitro fertilization and embryo transfer in normal responders later on GnRH antagonist administration
Yu Wu
Reproductive Medicine, Section of Obstetrics and Gynecology, Shanghai Jiaotong University Affiliated Offset People'due south Hospital, No. 650, New Songjiang Road, Shanghai, 201620 Mainland china
Find manufactures by Yu Wu
Xiaohong Gao
Reproductive Medicine, Department of Obstetrics and Gynecology, Shanghai Jiaotong University Affiliated First People's Hospital, No. 650, New Songjiang Route, Shanghai, 201620 China
Xiang Lu
Department of Reproductive Medicine, Shanghai Jiaotong University International Peace MCH Hospital, No. 910, Henshan Road, Shanghai, 200030 China
Ji 11
Section of Reproductive Medicine, Shanghai Jiaotong University International Peace MCH Hospital, No. 910, Henshan Road, Shanghai, 200030 China
Detect articles past Ji Xi
Shan Jiang
Department of Reproductive Medicine, Shanghai Jiaotong Academy International Peace MCH Hospital, No. 910, Henshan Road, Shanghai, 200030 Prc
Yin Sun
Department of Reproductive Medicine, Shanghai Jiaotong University International Peace MCH Hospital, No. 910, Henshan Road, Shanghai, 200030 China
Xiaowei Xi
Reproductive Medicine, Department of Obstetrics and Gynecology, Shanghai Jiaotong University Affiliated Commencement People's Hospital, No. 650, New Songjiang Road, Shanghai, 201620 China
Received 2014 Jun 12; Accepted 2014 October ii.
Abstract
Groundwork
The goal of this study was to assess the clan between endometrial thickness on the chorionic gonadotropin (hCG) day and in vitro fertilization and embryo transfer (IVF-ET) outcome in normal responders after GnRH antagonist administration.
Methods
A retrospective accomplice study was performed in normal responders with GnRH antagonist administration from Jan 2011–Dec 2013. Patients were divided into four groups according to endometrial thickness, as follows: <7 mm (grouping 1), > = vii- < 8 mm (grouping 2), > = 8- < xiv mm (group 3), and > =14 mm (grouping 4).
Results
A full of 2106 embryo transfer cycles were analyzed. The pregnancy rate (PR) was 44.87%.
The clinical pregnancy rate, ongoing pregnancy rate and the implantation rate (17.28%, 13.79%, 10.17%, respectively) were significantly lower in group i compared to the other three groups (p < 0.05). The miscarriage rate was higher in patients with endometrial thickness less than 7 mm. The clinical pregnancy rate, ongoing pregnancy rate and implantation charge per unit were highest in patients with endometrial thickness higher than 14 mm, but showed no difference in patients with those of endometrial thickness between 8-14 mm.
Conclusions
There is a correlation between endometrial thickness measured on hCG 24-hour interval and clinical outcome in normal responders with GnRH antagonist administration. The pregnancy rate was lower in patients with endometrial thickness less than 7 mm compared with patients with endometrial thickness more than vii mm.
Keywords: Endometrial thickness, IVF-ET, GnRH antagonist, Pregnancy rate
Background
In-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) are widely accustomed as effective handling for nigh causes of infertility. Gonadotropin-releasing hormone (GnRH) antagonist is now widely used in controlled ovarian stimulation cycles, which requires less follicle stimulation, and has lower gamble for ovarian hyperstimulation syndrome (OHSS) [1, 2]. A randomized controlled trial (RCT) showed that normal responders treated with the GnRH antagonist protocol exhibited the same high success rates every bit patients treated with the long GnRH agonist protocol. The GnRH adversary protocol is as effective and prophylactic as the long GnRH agonist protocol [3].
Age, quality of the embryo and endometrial receptivity are the almost important factors for the success of IVF. Endometrial thickness (EMT) has been accustomed as an indicator for endometrial receptivity, and cess of the endometrium in the midsagittal plane via transvaginal ultrasound is the standard procedure. Several studies have shown a pregnant correlation between pregnancy rate and endometrial thickness [4–7]. These studies reported a threshold of <seven mm with a significant reduction in the implantation rate and pregnancy charge per unit. Recently the offset systematic review and meta-analysis investigated both the independent predictive capacity and the prognosic value of endometrial thickness on pregnancy outcomesafter IVF. This written report plant that the probability of clinical pregnancy for an endometrial thickness ≤7 mm was significantly lower compared with cases with endometrial thickness >7 mm (23.iii% versus 48.1%) and OR was 0.42 (95% CI 0.27–0.67) [five]. There are few studies examining the association between endometrial thickness and clinical outcome in the GnRH antagonist protocol. The aim of this study was to assess the association between endometrial thickness on the HCG day and IVF outcome in normal responders after GnRH adversary assistants.
Methods
This study was reviewed and approved by the Institutional Review Lath and Ethics Committee of Shanghai First People'due south Infirmary, China. This written report is a retrospective accomplice report and analyzed 2106 normal responders in International Peace MCH Hospital Shanghai Jiaotong University. All fresh embryo transferred patients after GnRH antagonist assistants between Jan. 2011 and Dec. 2013 was included except poor responders according to the Bologna criteria [8] and patients with polycystic ovary syndrome (PCOS). Patients with abnormal uterine cavity per HSG or hysteroscopy were excluded from this study.
rFSH/HMG (rFSH-Gonal F-Merck Serono, Puregon-MSD, HMG Lizhu China) was initiated at a dosage of 150 U-225 U per twenty-four hour period on 24-hour interval ii of the bike. The ovarian response was monitored by ultrasound and serum LH, E2 and P on day 6 (stimulation day five). The demand for boosted doses of rFSH/HMG was determined based on follicular maturation, every bit assessed by ultrasound and E2 measurement. The GnRH antagonist (Cetrotide 0.25 mg-Merck Serono) 0.25 mg/day was added when at least 1 follicle reached 14 mm in diameter until hCG administration. When at least iii follicles had reached a diameter of 18 mm, a dose of hCG (hCG, Lizhu China) 6000 U was given and oocyte retrieval was performed 36 hours later using vaginal ultrasound guided follicle aspiration. The endometrial thickness was measured in the midsagittal plane via transvaginal ultrasound on the day of hCG administration. A maximum of 3 embryos were transferred after 2 or three days in culture.
Luteal support was administered by intramuscular progesterone (dose forty mg/day) beginning on the day of oocyte retrieval.
Clinical pregnancy was defined as the presence of at least a gestational sac on ultrasound 28 days afterward embryo transfer. Ongoing pregnancy was divers as the presence of at least one fetus with centre activity more than 12 gestational weeks. Implantation rate was calculated as the number of sacs with fetal centre shell over full embryos transferred.
All patients were divided into ane of the following 4 groups according to their endometrial thickness: group 1 (n = 29): <seven mm; grouping two (n = 162): ≥7 mm to <8 mm; grouping 3 (north = 1852): ≥viii mm to <14 mm; grouping four (n = 64): ≥14 mm.
Statistical methods
Statistical analysis was performed using the statistical parcel for Social Sciences (version 14, SPSS Inc, Chicago IL). The X2 test, t-test and ANOVA were used. P <0.05 was considered as statistically significant.
Results
A total of 2106 women aged 21–39 with fresh embryo transfer were included in the analysis. The endometrial thickness on the hCG twenty-four hours ranged from five mm to 18.7 mm. The overall pregnancy rate was 44.87%. The clinical pregnancy rate was significantly lower in cases with endometrial thickness beneath 7 mm. In addition, no pregnancy was observed in the patients with endometrial thickness less than 6 mm (Figure1). Co-ordinate to the pregnancy rate in Figurei (Group1: pregnancy rate <30%, Group2: pregnancy rate 30-xl%, Group 3: pregnancy rate 40-50% and Grouping 4: pregnancy charge per unit >l%), the patients were divided into 4 groups as previously described.
Clinical pregnancy rates according to endometrial thickness.
The demographic characteristics of the groups are shown in Tabular array1. Historic period, baseline FSH, and baseline E2 were similar among the four groups. More patients in Group 1 had a previous IVF endeavour. Identical results were obtained amidst these groups with regard to the duration of ovarian stimulation, elapsing of GnRH antagonist assistants, and serum E2 concentration on hCG day (Tableii). In that location were no significant differences among these groups. Moreover, the retrieved oocyte number, transferred embryo number, fertilization charge per unit and cleavage charge per unit were similar amid these groups (Table3).
Table i
Demographic and pretreatment characteristics
| Grouping 1 | Group 2 | Grouping 3 | Group iv | |
|---|---|---|---|---|
| N = 29 | N = 162 | N = 1852 | N = 63 | |
| Mean age | 33.12 ± 3.46 | 32.34 ± iv.02 | 31.89 ± three.67 | 31.98 ± 4.16 |
| No. of Previous IVF attempts | ||||
| None | 15(51.72%)* | 124(76.54%) | 1390(75.05%) | 51(fourscore.95%) |
| Ane | ten(34.48%) | xxx(eighteen.51%) | 374(xx.nineteen%) | xi(17.46%) |
| 2 or more | 4(13.79%) | 8(iv.94%) | 87(iv.70%) | 1(1.75%) |
| Baseline FSH(U) | 7.84 ± 2.44 | eight.13 ± 2.12 | 8.87 ± 5.28 | viii.89 |
| Baseline E2 (pmol/L) | 167.71 ± ninety.66 | 184.48 ± 160.48 | 169.85 ± 253.51 | 132.88 ± 57.19 |
*P < 0.05.
Tabular array 2
Outcome of ovarian stimulation
| Group 1 | Group 2 | Group 3 | Grouping 4 | |
|---|---|---|---|---|
| N = 29 | N = 162 | North = 1852 | N = 63 | |
| Total dose of Gn | 2137.three | 2109.1 | 2145.6 | 2089.45 |
| Duration of Gn | viii.55 ± ane.45 | eight.52 ± i.59 | 8.67 ± 1.49 | 8.86 ± 1.45 |
| Duration of antagonist | 3.68 ± 0.81 | 3.59 ± 1.21 | 3.67 ± 1.22 | 3.62 ± 1.24 |
| Serum E2 on hCG mean solar day | 9238 ± 1902.29 | 10457 ± 5391.63 | 10166.89 ± 6192.71 | 9962 ± 4662.25 |
Table 3
Issue of pre-embryonic development
| Group 1 | Grouping two | Group 3 | Group iv | |
|---|---|---|---|---|
| N = 29 | N = 162 | North = 1852 | North = 63 | |
| IVF/ICSI | 20/nine | 129/33 | 1387/475 | 53/10 |
| No. of oocyte retrieved | 9.34 ± six.0 | 10.78 ± five.41 | 10.82 ± 5.threescore | eleven.02 ± 4.59 |
| No. of oocyte fertilized | seven.three | 8.0 | 8.1 | 8.v |
| No. of embryo transferred | 2.03 ± 0.57 | 2.01 ± 0.39 | 2.02 ± 0.37 | 2.07 ± 0.32 |
| No. of embryo cryopreserved | 2.72 ± 3.68 | 3.01 ± 2.96 | two.97 ± 2.94 | ii.88 ± two.89 |
The clinical pregnancy charge per unit, ongoing pregnancy rate and implantation rate increased with an increase in endometrial thickness. The clinical pregnancy rate, ongoing rate and implantation rate (17.28%, xiii.79%, ten.17%, respectively) were everyman in group i and were significantly lower than the other three groups (p < 0.05). The miscarriage charge per unit was higher in patients with endometrial thickness less than 7 mm. Among patients with endometrial thickness between 7 mm to 8 mm, the clinical pregnancy rate and implantation charge per unit was lower than that of patients with endometrial thickness more 8 mm, merely this divergence was not pregnant. Merely the ongoing pregnancy rate was significantly lower than that in patients with thick endometria (≥14 mm). The clinical pregnancy rate, ongoing charge per unit and implantation rate (52.38%, 47.62%, and 38.17%, respectively) were highest in patients with an endometrial thickness greater than 14 mm (Tablefour).
Table 4
Clinical event
| Group 1 | Group 2 | Group iii | Group 4 | |
|---|---|---|---|---|
| Due north = 29 | N = 162 | N = 1852 | Northward = 63 | |
| Clinical pregnant rate | 17.24%* | 38.27 | 45.63% | 52.38% |
| (5/29) | (62/162) | (845/1852) | (33/63) | |
| Miscarriage rate | 20% | 11.29% | 10.30% | 9.09% |
| (i/v) | (7/62) | (87/845) | (3/33) | |
| Ongoing rate | 13.79%* | 32.10%* | 38.23% | 47.62% |
| iv/29 | 52/162 | 708/1852 | xxx/63 | |
| Implantation charge per unit | 10.17%* | 23.92% | 29.80 | 38.17% |
*P < 0.05.
Among 29 patients with thin endometrium (Grouping i), 19 patients was secondary infertility before they were included in the study. Still the number of the patients with previous IVF effort in this Group was higher which may have affected the event; nevertheless the pregnancy rate in patients in starting time bike was quite depression (6.7%, ane/15). The pregnancy rate was 40% amid patients in second cycle (4/x), and three of 4 patients among them who had an endometrial thickness more than than viii mm in previous long GnRH agonist protocol cycle got pregnant in this GnRH adversary cycle.
Discussion
Endometrial receptivity is one of the most important factors in predicting pregnancy later on in-vitro fertilization and embryo transfer. Endometrial thickness has been utilized as an private indicator for endometrial receptivity and is measured in the midsagittal airplane via transvaginal ultrasound, which is considered as a non-traumatic and a uncomplicated method [9]. The endometrial thickness measured on the 24-hour interval of hCG administration is well-nigh often used.
The effect of endometrial thickness on the success of IVF-ET had been evaluated past many studies [iv–seven, ten, 11]. Recent studies accept reported a threshold of <vii mm with a significant reduction in the implantation rate and pregnancy charge per unit [5–7]. Meta-assay showed that the probability of clinical pregnancy in patients with endometrial thickness less than 7 mm was significantly lower compared to patients with endometrial thickness greater than 7 mm [23.three% versus 48.1%, OR 0.42 (95% CI 0.27–0.67)]. Positive and negative predictive values for the outcome of clinical pregnancy were 77% and 48%, respectively [5]. Kumbak likewise found that the clinical pregnancy charge per unit was 26%, miscarriage rate was 31% and live birth rate was 17% among patients with endometrial thickness less than 7 mm. However, these results were relatively practiced when the patient historic period was <35 years or the number of oocytes retrieved was over five or the number of available embryos to transfer was ≥3 [seven]. Thus, no conclusive cutting-off value of endometrial thickness has been established.
The findings of endometrium thicker than 14 mm are controversial. Several authors suggested a detrimental effect of endometrial thickness of ≥fourteen mm on pregnancy rate [12], while the results of other studies accept suggested that a thick endometrium increased the pregnancy charge per unit [4]. Quintero reported a adult female who successfully conceived with an endometrial thickness of 20 mm [13].
Almost studies examining the association between endometrial thickness and clinical outcome were performed using the GnRH agonist protocol. With the antagonist protocol being increasingly used, Al-Inany updated the Cochran review in 2011. Forty-five randomized trials (RCT) (n =7511) were included. The results showed that there was no evidence of a statistically significant departure in the rates of live births (OR 0.86, 95% CI 0.69 to 1.08), and in that location was a statistically significant lower incidence of OHSS in the GnRH antagonist grouping (OR 0.43, 95% CI 0.33 to 0.57) [14].
The GnRH antagonist was also recently introduced in China. A RCT comparing the antagonist protocol with the agonist long protocol was performed in normal responders. Antagonist treatment with a 43.7% clinical pregnancy rate was more efficient and safer than treatment with a long protocol and demonstrated as high success rates [3]. In our study, the clinical pregnancy rate was 44.87% in the normal responder with GnRH antagonist assistants, which was consequent with the results described to a higher place.
There are few studies investigating the association between endometrial thickness and clinical outcome with GnRH antagonist administration. Nevertheless, these results are controversial [15, sixteen]. Our study is a retrospective cohort study examining the relationship between endometrial thickness and clinical outcome using the GnRH antagonist protocol in normal responders. These patients were aged 20–39 and patients with PCOS and poor responder were excluded. Our study showed a positive correlation between endometrial thickness and clinical outcome, which is consistent with several studies [6, 16]. There were merely 5 clinical pregnancies (17.24%) in our study, which had an endometrial line of less than 7 mm, of which one was lost. The number of previous IVF attempts was college in these patients which might bear on the pregnancy. Although the pregnancy rate was half dozen.7% in the patients in first cycle, the loftier previous IVF attempt is still a limitation of the study. The pregnancy rate amid these patients is similar to the pregnancy rate (23.3%) in recently meta-analysis although most women in the meta-analysis were conducted in long GnRH agonist protocol [5].
Patients with an endometrial thickness between seven–viii mm had a decreased pregnancy rate, only no significant divergence was shown when compared to patients with endometrial thickness in 8-14 mm.
Implantation is necessary for a successful pregnancy and requires salubrious endometrial receptivity [17]. The implantation rate (10.17%) was significantly lower in patients with thin endometrial thickness. Thicker endometria corresponded with college implantation rates. These findings were consistent with a clinical pregnancy rate and ongoing pregnancy rate results.
In patients with thicker endometria (≥14 mm), the clinical pregnancy rate, ongoing pregnancy rate and implantation rate increased, but with no difference with patients with endometrial thickness in eight-14 mm in our study. This finding was consequent with several recent studies demonstrating no reduction in pregnancy rate with a very thick endometrium [6, 12].
Our report has some limitations, the most important of which is its retrospective nature. Even so, we believe that the results are of involvement considering similar studies had been published with alien results.
Conclusions
The results of the present study identified a correlation between endometrial thickness measured on hCG day and clinical outcome in normal responders with GnRH adversary assistants.
Acknowledgements
The authors thank anybody in the Department of Reproductive Medicine in the International Peace MCH Infirmary for their scientific advice and encouragement. We thank the English professional service (http://webshop.elsevier.com/languageediting/) for their language editing.
Footnotes
Competing interests
The authors declare that they take no competing interests.
Authors' contributions
All authors made substantial contributions to the conception and design of this enquiry written report. YW acquired the data and wrote the manuscript. XWX critically revised the manuscript. All authors read and approved the concluding manuscript.
Correspondent Information
Yu Wu, Email: moc.361@818uwuy.
Xiaohong Gao, Email: moc.361@6090gnohoaixoag.
Xiang Lu, Email: moc.liamtoh@57gnaixuL.
Ji Xi, Electronic mail: moc.liamtoh@0002eeX.
Shan Jiang, Email: moc.anis@gnaij_ybnJ.
Yin Sun, E-mail: nc.anis@2171gniynus.
Xiaowei Eleven, E-mail: moc.621@6691iewoaixix.
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