Abstract
Purpose
To assess whether embryo transfer (ET) technique can influence the clinical pregnancy rate (CPR) and its correlation with the embryo transfer difficulty.
Design
This single center retrospective cohort analysis of fresh and frozen single blastocyst transfers performed between January 2016 and December 2021 included fresh and frozen single blastocyst transfers performed during the study timeframe. Direct technique was the only one used from January 2016 to September 2017. From September 2017 to March 2019, the choice between the two techniques was given by randomization, due to a clinical trial recruitment. From April 2019, only the afterload technique was used. Preimplantation genetic testing cycles and gamete donation procedures and cycles performed with external gametes or embryos were excluded. CPR was the primary outcome, while difficult transfer rate the secondary one. Univariate and multivariate logistic regressions were performed.
Results
During the period, 8,189 transfers were performed. CPR of the afterload group resulted significantly higher compared to the direct group (44.69% versus 41.65%, OR 1.13, 95% CI 1.02–1.25, p = 0.017) and the rate of difficult transfers two-thirds lower (9.06% versus 26.85%, OR 0.27, 95% CI 0.24–0.31, p < 0.001).
Conclusion
Our study demonstrated that CPR is significantly affected by the ET technique. In particular, with the afterload protocol, both CPR and easy transfer rates increased.
Trial registration
http://clinicaltrials.gov registration number: NCT05364528, retrospectively registered on 3rd of May 2022
Supplementary Information
The online version contains supplementary material available at 10.1007/s10815-023-02957-y.
Keywords: ART, Embryo transfer, Technique, Difficult transfer, Clinical pregnancy rate
Introduction
In assisted reproductive technologies (ART), every single step has its own fundamental role in pregnancy achievement, including the delicate phase of embryo transfer (ET) [1, 2]. Several variables seem to concur to the efficacy of the ET, such as the difficulty of the procedure [3–5], its duration [6], the type of catheter used [7–9], the volume and type of transfer media [10] [11–14], the presence of cervix or catheter tip contamination [15, 16], the use of ultrasound guidance [7–9], and the occurrence of retained embryos [2]. Among the above variables, the difficulty of ET has represented, in recent times, an emerging theme for the success of ART cycle [5]. According to several studies, subjects with an easy or intermediate ET show a significantly higher clinical pregnancy rate (CPR) than those with a difficult one [5, 17]. The difficulty of the ET procedure may depend on unmodifiable variables such as the patient’s characteristics [18] and other purely technical variables that can be modified or increased such as the type of the catheter and the expertise of the single operator. Considering the type of catheter, despite it being generally recognized that soft and flexible ones may avoid any endometrial lining trauma and embryo toxicity [19], it is known that they can lead to an increased rate of difficult transfers [20]. Concerning the impact of the operator on the success of the ET procedure, several studies assessing the possible correlation between the clinician [21] or the embryologist [22] and obstetrical outcomes led to promising results, although still conflicting [23–25].
The present study represents the logic progression of a prospective randomized controlled trial (RCT) performed in the same setting on a smaller population [26] comparing direct (single step) and afterload (double step) catheter techniques. It showed that the afterload technique had a significantly lower rate of difficult transfer (9.66% versus 38.64%, p < 0.001). It also observed a difference in CPR between the two groups, despite not statistically different, given the study was not powered to detect this outcome [26]. Therefore, the present retrospective analysis was carried out to highlight the difference of direct and afterload ETs in terms of CPR and its correlation with the ET difficulty, in a larger sample with statistical power to detect CPR difference between the 2 transfer protocols.
Materials and methods
Design and study population
This retrospective cohort study included fresh single day-5 and frozen single day-5 and day-6 blastocyst transfers performed at Humanitas Fertility Center, a university affiliated tertiary care ART center, between January 2016 and December 2021. Preimplantation genetic testing (PGT) cycles, gamete donation procedures, cycles performed with external either gametes or embryos, and day-7 blastocyst transfers were excluded.
Intervention description
Different induction protocols were used according to the guidelines [27, 28]. Concerning fresh ETs, a support of the luteal phase was provided by a supplementation of vaginal micronized progesterone (600 mg daily). Cryopreservation with subsequent frozen embryo transfer (FET) was performed in patients with high risk of ovarian hyperstimulation syndrome (OHSS), inadequate endometrial growth, premature progesterone surge, or in case of additional embryos from a previous COS cycle. For FETs, three different protocols were used for endometrial preparation: natural cycles (NC-FET), modified natural cycles (mNC-FET) with human chorionic gonadotropin (hCG) triggering, and artificial replacement cycles (AR-FET), as previously described [29]. Fresh transfer was performed only in D5 and FET 120 hours after progesterone trigger, in both D5 and D6 blastocyst. No differences in fresh vs. frozen single blastocyst transfer CPR were considered due to other authors and our previous data [30, 31]. During all the considered period, the same vitrifying protocol was implemented [32].
Blastocyst grading was defined according to the Istanbul consensus [33] and the development rate [1–4], inner cell mass [1–3], and trophectoderm [1–3] were scored for analysis in a numerical manner, yielding 3 subgroups (poor, intermediate, and top quality). The procedure was standardized as far as possible in order to minimize bias [34]. No mock transfers were performed. The patient had to lay down in lithotomy position in a surgical room with a controlled light, pressure, humidity, and temperature setting, next to the embryology laboratory, preferably with a full bladder. No anesthesia or other medication was used. A sterile steel speculum was used to expose the cervix, cleansing it with warm sterile physiological solution. All ETs were performed through a transabdominal US guidance held by a trained nurse. The transfer point location was pre-measured in accordance with Frankfurter (Frankfurter et al., 2003). As previously described [26], two different techniques were used: the direct ET consists in inserting together a straight outer guiding catheter and an inner soft catheter (Cook k-soft-5000 or Cook SPPE) without any prior trial; while the afterload, ET is performed with a rounded bulb tip catheter (Cook K-Jets-551910-S) and consists in firstly inserting an outer guiding slightly stiff catheter, with a pre-shaped curve, and secondly an inner ultra-soft catheter with a rounded bullet tip. The embryos were loaded by the embryologist in approximately 30 μL of hyaluronic enriched medium flanked with small air bubbles: the latter, indeed, can help with ultrasound visualization and may also play a role in the proper placement of the embryo [2]. Direct technique was the only one used from January 2016 to September 2017. In the clinical trial recruitment period (from September 2017 to March 2019), the use of the two techniques was given by randomization. After RCT data analysis (from April 2019), only the afterload technique was used. In all the timeframes included in the present study, the operators never had chance to personally choose the technique: in the first and third period, only one catheter was available, in the second one, the technique was randomized. Regarding pregnancy assessment and follow-up, serum beta-hCG was tested 12 days after ET and monitored every 48 h until a cut-off of 1,000 IU/mL was reached. Two weeks later, a TV-US was performed to determine the presence and the number of gestational sacs and fetal viability [35].
Main outcomes and variable description
The primary outcome was clinical pregnancy rate (CPR), defined as “the number of pregnancies (diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy) × 100 divided by the number of embryo transfer cycles” [36]. We preferred CPR over LBR (live birth rate) for two main reasons: as stated in the ESHRE Maribor Consensus 2021 “LBR is a generally accepted and important parameter for measuring ART success although it is a parameter that is related to many factors, even apart from the ART” and the survey showed “large agreement on considering CPR a relevant parameter to evaluate ET” [36]. The secondary outcome was the difficult transfer rate in the two ET techniques, defined, by the same definition of the previous RCT [26], as the “number of difficult or suboptimal transfers defined as: advancement of the outer sheath (specific for the direct transfer), multiple attempts, use of force, required manipulation, use of a stylet or tenaculum, dilatation, or use of a different catheter, × 100 divided by the number of ET cycles.” The confounding variables considered for the statistical analysis were female and male age, female body mass index (BMI), female smoking habit, ovarian reserve, expressed by day-2 follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH), infertility type (primary or secondary), infertility duration, causes of infertility (tubal factor, endometriosis, anovulatory, reduced ovarian reserve, multiple female factors, male factor, both male and female factors, idiopathic, and other infertility causes), obstetrical history, and blastocyst grading. Difficult transfer was considered a confounding variable for the primary outcome since it has already been demonstrated that it can significantly affect the CPR [5], [17]. Given the temporal distribution of the two techniques over time, over 4 years, the year of the procedure was also included as a confounding factor.
Statistical analysis
Data were expressed as number and percentage, if categorical, or mean and standard deviation if continuous. Differences between afterload and direct groups were explored with Chi-square test if the variable was categorical, or with unpaired t-Student test if continuous approximately Gaussian distributed, or with Mann–Whitney test otherwise. The adherence to Gaussian distribution was assessed with Shapiro–Wilk test. All variables were initially analyzed by a univariate logistic regression, to identify potential factors affecting the occurrence of clinical pregnancy; those with a p value < 0.2 were then submitted to multivariable stepwise logistic regression analysis, and variables that lost their importance were excluded from the final model, which included only the variables associated to the outcome and their interaction, if relevant. Results of the stepwise regression analysis were expressed as odds ratio (OR) and 95% confidence interval (CI). Finally, we explored the impact of operator experience on the difficulty of transfer with each catheter through Mantel–Haenszel analysis of the operators’ total number of transfers performed and difficult transfers with different catheters. Only operators with at least 10 procedures per catheters were considered in this analysis. The interaction between difficult transfer and afterload technique in the total cohort and in a subgroup of frozen ETs was also analyzed.
All statistical analysis was carried out with Stata 15.0 (StataCorp. 2017. Stata Statistical Software: Release 15. College Station, TX: StataCorp LP). A p value of <0.05 was considered statistically significant.
Ethical approval and data protection
On April 27, 2022, Humanitas Ethical Committee approved the protocol that was also registered on http://clinicaltrials.gov (ID NCT05364528) before full data extraction. The procedures of the study adhered to the Declaration of Helsinki ethical principles for medical research involving human subjects. All patients included in the study were asked to sign a written consent to allow the use of their medical records for research purpose anonymously.
Results
During the 6-year period considered, 8,189 single blastocyst transfers were performed. Among these, 2,000 patients underwent direct ET and 6,189 patients underwent afterload ET. The follow-up for the primary outcome was completed in February 2022. Baseline sample characteristics and outcomes are expressed in Table 1. The afterload group was characterized by an older female (36.12 ± 4.0 versus 35.77 ± 4.03, p < 0.001) and male age (39.43 ± 5.68 versus 39.03 ± 5.28, p = 0.023), higher percentage of active smokers (20.05% versus 17.65%, p = 0.018), and higher levels of FSH (7.44 ± 5.88 versus 6.79 ± 2.46, p < 0.001). Moreover, afterload patients showed a higher percentage of tubal factor, reduced ovarian reserve, and mixed causes with respect to the direct group (p < 0.001). Lastly, 18.08% of patients in the afterload group already had a delivery compared to 15.15% in the direct group (p = 0.003), and 32.99% of blastocysts in the afterload group was considered poor quality vs. only the 26.97% in the direct one (p < 0.001). Afterload ET showed a percentage of difficult transfers which was almost one third compared to that of the direct ET, being, respectively, 9.06% and 26.85% (OR 0.27, 95% CI 0.24–0.31, p < 0.001). Overall, the CPR between the two groups was significantly different: 44.69% in afterload ET and 41.65% in direct ET (OR 1.13, 95% CI 1.02–1.25, p = 0.017). Table 2 shows the interaction between the two techniques and difficult transfer on CPR, corrected for female and male age, year of the procedure, and the grading of blastocysts. To perform this analysis, direct easy transfer was taken as reference (OR = 1). It means that if a variable shows an OR > 1, it may increase the CPR, compared to the reference (direct easy transfer) and, on the contrary, if the variable shows an OR < 1, it may decrease the CPR, compared to the same reference. Only the direct difficult ET resulted having a statistically significant p (<0.001), with an OR of 0.62 (95% CI 0.49–0.77) compared to direct easy transfer. Both easy and difficult ETs with afterload technique, on the contrary, showed the same CPR as an easy transfer performed with the direct method, OR 0.97 (95% CI 0.82–1.14) and 0.85 (95% CI 0.67–1.08), p 0.685 and 0.197, respectively). Therefore, while for the afterload method the presence of a difficult ET was not a limit, the CPR was reduced in difficult ET using the direct one. Lastly, among the various operators, a range of difficult transfers from 3.8 to 45.4% in the direct group and 0.8 to 20.5% in the afterload group was found (p < 0.001), as shown in Table 3. A Mantel–Haenszel analysis was then performed, and in 5 out of 15 (30%) operators, there were no differences in terms of difficulty between the two techniques (Table 4). As for the additional analysis in the frozen ET subgroup during the same timeframe, a total of 6,824 (83.33%) cycles were included in the analysis. Among these, in 5,065 (74.22%), an afterload ET was performed, while in 1,759 (25.78%), a direct ET. As shown in Supplementary Table 1, while there was a clear correlation between difficult transfer rates and the technique used (9.30% for afterload and 26.62% for direct, p < 0.001), the difference in CPR between the two groups was slightly not significant (p = 0.086). As for the interaction between the two techniques and difficult transfer on CPR, corrected for female and male age, year of the procedure, and the grading of blastocysts, only the direct difficult ET resulted significantly lower with an OR of 0.65 (95% CI 0.52–0.81, p < 0.001), as shown in Supplementary Table 2.
Table 1.
Baseline patients’ characteristics
| Variables | All transfers | Afterload transfers | Direct transfers | p value |
|---|---|---|---|---|
| Number | 8,189 | 6,189 | 2,000 | |
| Female age (years) | 36.03 ± 4.01 | 36.12 ± 4.00 | 35.77 ± 4.03 | <0.001 |
| Male age (years) | 39.34 ± 5.59 | 39.43 ± 5.68 | 39.03 ± 5.28 | 0.023 |
| Female BMI (kg/m2) | 22.03 ± 3.20 | 22.06 ± 3.24 | 21.93 ± 3.06 | 0.319 |
| Female smoking habit | 1,594 (19.47%) | 1,241 (20.05%) | 353 (17.65%) | 0.018 |
| FSH (mUI/mL) | 7.28 ± 5.26 | 7.44 ± 5.88 | 6.79 ± 2.46 | <0.001 |
| AMH (ng/mL) | 3.70 ± 3.04 | 3.66 ± 2.98 | 3.82 ± 3.21 | 0.110 |
| Infertility type (% primary) | 4,837 (59.07%) | 3,676 (59.40%) | 1,161 (58.05%) | 0.287 |
| Infertility duration (years) | 4.55 ± 2.73 | 4.54 ± 2.61 | 4.59 ± 3.07 | 0.220 |
| Infertility factors: | ||||
| Tubal factor | 672 (8.21%) | 649 (10.49%) | 23 (1.15%) | <0.001 |
| Endometriosis | 222 (2.71%) | 165 (2.67%) | 57 (2.85%) | 0.066 |
| Anovulation | 237 (2.89%) | 159 (2.57%) | 78 (3.90%) | 0.002 |
| Reduced ovarian reserve | 448 (5.47%) | 432 (6.98%) | 17 (0.80%) | <0.001 |
| Multiple female factors | 214 (2.61%) | 145 (2.34%) | 69 (3.45%) | 0.007 |
| Male factor | 3,185 (38.89) | 2,422 (39.13%) | 763 (38.15%) | 0.433 |
| Male and female factors | 1,091 (13.32%) | 1,059 (17.11%) | 32 (1.60%) | <0.001 |
| Idiopathic | 1,262 (15.41%) | 973 (15.72%) | 289 (14.45%) | 0.171 |
| Other factors | 50 (0.61%) | 40 (0.65%) | 10 (0.50%) | 0.465 |
| Previous deliveries | 1,422 (17.36%) | 1,119 (18.08%) | 303 (15.15%) | 0.003 |
| Previous miscarriages | 2,803 (34.23%) | 2,121 (34.27%) | 682 (34.10%) | 0.889 |
| Blastocyst grading | n = 7525 | n = 5675 | n =1850 | <0.001 |
| Top quality | 1,200 (15.95%) | 904 (15.93%) | 296 (16.0%) | 0.943 |
| Medium quality | 3,954 (52.54%) | 2,899 (51.08%) | 1,055 (57.03%) | |
| Poor quality | 2,371 (31.51%) | 1,872 (32.99%) | 499 (26.97%) | <0.001 |
| Difficult transfer | 1,098 (13.41%) | 561 (9.06%) | 537 (26.85%) | <0.001 |
| CPR | 3,599 (43.95%) | 2,766 (44.69%) | 833 (41.65%) | 0.017 |
BMI, body mass index; FSH, follicle stimulating hormone; AMH, anti-Mullerian hormone; CPR, clinical pregnancy rate; data are reported as mean ± standard deviation or number and percentage
Table 2.
Interaction between technique and difficult ET on CPR
| OR (95% CI) | p value | |
|---|---|---|
| Direct easy ET | 1 | |
| Afterload easy ET | 0.97 (0.82–1.14) | 0.685 |
| Afterload difficult ET | 0.85 (0.67–1.08) | 0.197 |
| Direct difficult ET | 0.62 (0.49–0.77) | <0.001 |
Reference value: direct easy ET (OR = 1). CPR, clinical pregnancy rate; ET, embryo transfer. Results are reported as odds ratio (OR) and confidence interval (CI) and corrected by female and male age, year of procedure and blastocyst grading, and relative interactions. Standard errors of results were adjusted by clustering for the same couple
Table 3.
Interaction between technique and difficult ET among different operators
| All transfers | Afterload transfers | Direct transfers | OR (95% CI) | p | |
|---|---|---|---|---|---|
| N | 8,189 | 6,189 | 2,000 | ||
| Difficult transfers | 1,098 (13.41%) | 561 (9.06%) | 537 (26.85%) | 0.27 (0.24–0.31) | <0.001 |
| Average rate of difficult transfers per operator % (SD) | 13.4 (34.0) | 8.6 (28.0) | 26.6 (44.2) | <0.001 | |
| Range of difficult transfer per operator (%) | 1.9–25.3 | 0.8–20.5 | 3.8–45.4 |
SD, standard deviation; OR, odds ratio; CI, confidence interval
Table 4.
Mantel–Haenszel analysis of operators’ total number of transfers and of difficult transfers
| Operator ID | Number of difficult transfer/total number of transfers | Number of afterload difficult transfers/total number of afterload transfers | Number of direct difficult transfers/total number of direct transfers | OR (95% CI) | p |
|---|---|---|---|---|---|
| 1 | 84/548 | 37/390 (9.49%) | 47/158 (29.75%) | 0.25 (0.15–0.41) | <0.001 |
| 2 | 19/114 | 12/85 (14.12%) | 7/29 (24.14%) | 0.52 (0.18–1.49) | 0.213 |
| 3 | 48/715 | 26/538 (4.83%) | 22/177 (12.43%) | 0.36 (0.20–0.65) | 0.001 |
| 4 | 4/206 | 1/126 (0.79%) | 3/80 (3.75%) | 0.21 (0.02–2.05) | 0.135 |
| 5 | 114/590 | 43/418 (10.329%) | 71/172 (41.28%) | 0.16 (0.10–0.26) | <0.001 |
| 6 | 40/638 | 24/488 (4.92%) | 16/150 (10.67%) | 0.43 (0.22–0.84) | 0.011 |
| 7 | 80/509 | 36/412 (8.74%) | 44/97 (45.36%) | 0.12 (0.07–0.20) | <0.001 |
| 8 | 31/161 | 5/46 (10.87%) | 26/115 (22.61%) | 0.42 (0.15–1.18) | 0.089 |
| 9 | 84/591 | 40/446 (8.97%) | 44/145 (30.34%) | 0.23 (0.14–0.37) | <0.001 |
| 10 | 54/590 | 40/472 (8.47%) | 14/118 (11.86%) | 0.69 (0.36–1.31) | 0.254 |
| 11 | 99/619 | 39/471 (8.28%) | 60/148 (40.54%) | 0.13 (0.08–0.22) | <0.001 |
| 12 | 78/448 | 35/325 (10.77%) | 43/123 (34.96%) | 0.22 (0.13–0.38) | <0.001 |
| 13 | 73/478 | 22/343 (6.41%) | 51/135 (37.78%) | 0.11 (0.06–0.21) | <0.001 |
| 14 | 132/522 | 80/390 (20.51%) | 52/132 (39.39%) | 0.40 (0.26–0.61) | <0.001 |
| 15 | 31/536 | 19/390 (4.87%) | 12/146 (8.22%) | 0.57 (0.27–1.21) | 0.140 |
Only operators with at least 10 procedures per catheter were considered. ID, identity; OR, odds ratio; CI, confidence interval
Discussion
The results highlight that in a large real-world cohort of patients, the CPR is influenced by the ET technique. Afterload ET leads to a higher CPR compared with the direct one. Moreover, as a confirmation of the previous RCT [26], the afterload technique showed a percentage of difficult transfers which was almost one third compared to the direct technique (respectively, 9.06% and 26.85%, p < 0.001). Regardless of the difficulty of transfer, the afterload group resulted in a significantly higher CPR respect to the direct one. On one hand, by analyzing the interaction between afterload method and difficult transfers, the positive effect of the afterload method on CPR seems to be mediated by its capability to significantly reduce the difficult ET rate. On the other hand, as shown in Table 2, CPR for difficult afterload ETs is like the one with the easy direct ETs (OR 0.85 (95% CI 0.67–1.08)). The superiority of the afterload technique compared to the direct one is also supported by the sample’s characteristics: despite the mean female and male age, female BMI, number of female active smokers, and poor-quality blastocyst being higher in the afterload group, the latter showed a significant reduction of difficult transfers and a higher CPR. Despite live birth rate being considered the most relevant ART outcome [37], we decided to use CPR as primary outcome to reduce the biases related to the high early abortion rate in older female age population and other confounding factors, being firmly convinced that CPR is more related to the transfer technique. A possible reason for our results is that, as already highlighted by several authors [38, 39], with the afterload technique, the embryo is subjected to less manipulations since it is not exposed until its entrance in the uterine cavity, leading to a reduced risk of negative outcomes. Moreover, the afterload technique may have a shorter learning curve compared to the direct counterpart, allowing faster positive results. It is nowadays established in the ART community that an easy embryo transfer is fundamental for achieving high success rates, and the choice of the catheter type and consequently the technique may play a crucial role [40–42] [43] [19] [44]. Nevertheless, concerns whether the operator could influence the success of ET procedures are still present. Several studies carried out so far have compared the operator’s experience and pregnancy rate (PR), leading to conflicting and inconclusive results, mainly due to the insufficient sample size [21]. As already demonstrated by a study conducted at Humanitas Fertility Center [21], there is a wide difference in PR between the various operators, independently of their experience; however, in a RCT carried out in the same setting [26], it was shown that the afterload technique, by facilitating the procedure, improved the operator’s performance in terms of PR. Therefore, we can infer that the afterload protocol leads to a higher homogeneity in difficult transfer rate and consequently to a global improvement of the outcomes. Simulation training for ET may play a relevant role in achieving operators’ skills and trainees’ confidence [45, 46] in order to lower the rate of difficult transfers, even if evidences on the improvement in pregnancy outcomes are still conflicting [47]. Just a few reports comparing direct and afterload techniques can be found in literature; indeed, in August 2021, the first prospective RCT [26], was published. Even if the study was not conceived to evaluate this outcome, the direct group showed a CPR more than 5% lower (p = 0.239) with respect to afterload group. Since it was not ethical to perform a RCT after the results of this study clearly showed the inferiority of direct over afterload technique, a cohort study was carried out. The sub-analysis on the frozen ET subgroup was carried out in order to reproduce the population sample of the previous study that was performed only on frozen ETs [26]. The main limitations of the study include the difference in sample sizes between the two groups and the wide range of time considered, during which, due to the constant training, the performance of the physicians had improved. In addition, the present study included a wide variability of operators (15 operators performing the procedures), making the study difficult to replicate for smaller centers but allowing a high intra-study reproducibility. A further possible reason of concerns and possible difficulty to replicate the study is the high prevalence of difficult transfer, probably due to the broad definition we used. A recent monocentric analysis found a prevalence of 7.7%, that is much lower than what we found in the present study [17]. Since there is not a standardized definition of difficult ET, it is difficult to make an accurate comparison of studies and it may be a possible explanation why in the literature the prevalence of difficult ETs is still variable. Similarly, we did not assess a score for the difficulty of ET (e.g., from multiple attempts to the use of a stylet or a tenaculum or cervix dilatation).
One possibility to reduce the rate of difficult transfers could be to perform a mock transfer in patients at risk for a difficult procedure, i.e., patients with an history of previous difficult transfer or previous cervical surgery or with unfavorable ultrasound characteristics such as in cases of extremely retroverted or rotated uterus or of an abnormal uterocervical angle. A dummy or mock transfer is defined as a transfer performed prior to ET that “allows the clinician to assess the uterine cavity and the utero-cervical angle.” In order to minimize the risk of a difficult transfer, this also assists in the choice of the most suitable catheter [48]. On the contrary, our data support the possibility of the a priori choice of the afterload technique and the consequent simplification of the procedures, especially in high patients-volume centers with many operators of varying experience levels. To conclude, we demonstrated that the positive effect of afterload technique on CPR is mediated by its ability to reduce difficult transfers. Since it is hard to find in literature studies that focus on direct and afterload protocols, additional research should be performed to support our findings and to extend knowledge regarding these ET techniques, in other clinical settings.
Supplementary information
(DOCX 14 kb)
Acknowledgements
The authors thank all the embryologists, gynecologist, nurses, and staff working at Humanitas Fertility Center, Rozzano, Milan, Italy.
Author contribution
F. C. and P. E. L.-S. were involved in the study concept and design, analyzed data, and wrote the manuscript. V. I., C. R., and T. C. contributed to the acquisition of data, analyzed data, wrote the manuscript, and contributed to bibliography updating. E. M. analyzed data, wrote the manuscript, and supervised the analysis. E. A. contributed to the acquisition of data. A. B. critically revised the manuscript and helped for data analysis.
Data availability
The dataset underlying this article is available in Zenodo repository and can be accessed, on reasonable request to the corresponding author, since it includes sensitive data.
Declarations
Ethics approval
Approval was obtained from the ethics committee of the Humanitas institutional review board. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.
Consent to participate
Informed consent was obtained from all individual participants included in the study.
Consent for publication
Patients signed informed consent regarding publishing their data.
Competing interest
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
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Data Availability Statement
The dataset underlying this article is available in Zenodo repository and can be accessed, on reasonable request to the corresponding author, since it includes sensitive data.