Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH)

STUDY QUESTION: Does endometrial scratching in women with one failed IVF/ICSI treatment affect the chance of a live birth of the subsequent fresh IVF/ICSI cycle? SUMMARY ANSWER: In this study, 4.6% more live births were observed in the scratch group, with a likely certainty range between -0.7% and +9.9%. WHAT IS KNOWN ALREADY: Since the first suggestion that endometrial scratching might improve embryo implantation during IVF/ICSI, many clinical trials have been conducted. However, due to limitations in sample size and study quality, it remains unclear whether endometrial scratching improves IVF/ICSI outcomes. STUDY DESIGN, SIZE, DURATION: The SCRaTCH trial was a non-blinded randomised controlled trial in women with one unsuccessful IVF/ICSI cycle and assessed whether a single endometrial scratch using an endometrial biopsy catheter would lead to a higher live birth rate after the subsequent IVF/ICSI treatment compared to no scratch. The study took place in 8 academic and 24 general hospitals. Participants were randomised between January 2016 and July 2018 by a web-based randomisation programme. Secondary outcomes included cumulative 12-month ongoing pregnancy leading to live birth rate. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with one previous failed IVF/ICSI treatment and planning a second fresh IVF/ICSI treatment were eligible. In total, 933 participants out of 1065 eligibles were included (participation rate 88%). MAIN RESULTS AND THE ROLE OF CHANCE: After the fresh transfer, 4.6% more live births were observed in the scratch compared to control group (110/465 versus 88/461, respectively, risk ratio (RR) 1.24 [95% CI 0.96-1.59]). These data are consistent with a true difference of between -0.7% and +9.9% (95% CI), indicating that while the largest proportion of the 95% CI is positive, scratchin

Endometrial preparation methods in frozen-thawed embryo transfer

One in six couples suffer from infertility, and many undergo treatment with in-vitro fertilization (IVF). Given that IVF often results in more embryos than can be transferred during one embryo transfer cryopreservation of the supernumerary embryos has been an important addition to IVF. In recent years, improvements in cryo-thaw technologies have increased interest in the transfer of frozen thawed embryos as a means of increasing the efficacy of the procedure and to encourage the transfer of fewer embryos, in order to reduce the costs and morbidity associated with multiple pregnancy. In the Netherlands, in 2015, over half of all embryos transferred was a frozen-thawed embryo. A key element of successful freeze thaw treatment is the appropriate preparation of the endometrium to receive embryos. In order to reach optimal synchronization of embryo and endometrium various methods of preparation have been developed. In the thesis “Endometrial preparation methods in frozen-thawed embryo transfer”pregnancy and live birth rates of the various methods of endometrium preparation described in recent literature were compared. None of the methods of endometrium preparation methods could be preferred over another. Comparing the cost-efficiency of two of these methods of endometrial preparation methods similar conclusion were drawn. Therefore, the best method to prepare the womb for receiving a frozen and thawed embryo; it is up to the patient to decide. The second part of the thesis focusses on improving the efficiency of one of the methods of endometrium preparation. In so-called natural cycle frozen-thawed embryo transfer the patients’ own menstrual cycle determines planning of thawing and transferring. Various circumstances that might disrupt the synchronization between embryo and endometrium have been suggested. Insufficient endometrium thickness, elevated progesterone levels and the presence of an LH surge are suggested disruptors of endometrium – embryo synchronization. Even though these circumstances are often observed during natural cycle frozen-thawed embryo transfer they seem to have little consequences with regard to pregnancy rates. Extensive hormonal monitoring also does not help identifying patients that will conceive from those that do not. From an efficiency point of view refraining from monitoring of various hormonal measurements and of the endometrial thickness can be considered

Endometrial preparation methods in frozen-thawed embryo transfer

One in six couples suffer from infertility, and many undergo treatment with in-vitro fertilization (IVF). Given that IVF often results in more embryos than can be transferred during one embryo transfer cryopreservation of the supernumerary embryos has been an important addition to IVF. In recent years, improvements in cryo-thaw technologies have increased interest in the transfer of frozen thawed embryos as a means of increasing the efficacy of the procedure and to encourage the transfer of fewer embryos, in order to reduce the costs and morbidity associated with multiple pregnancy. In the Netherlands, in 2015, over half of all embryos transferred was a frozen-thawed embryo. A key element of successful freeze thaw treatment is the appropriate preparation of the endometrium to receive embryos. In order to reach optimal synchronization of embryo and endometrium various methods of preparation have been developed. In the thesis “Endometrial preparation methods in frozen-thawed embryo transfer”pregnancy and live birth rates of the various methods of endometrium preparation described in recent literature were compared. None of the methods of endometrium preparation methods could be preferred over another. Comparing the cost-efficiency of two of these methods of endometrial preparation methods similar conclusion were drawn. Therefore, the best method to prepare the womb for receiving a frozen and thawed embryo; it is up to the patient to decide. The second part of the thesis focusses on improving the efficiency of one of the methods of endometrium preparation. In so-called natural cycle frozen-thawed embryo transfer the patients’ own menstrual cycle determines planning of thawing and transferring. Various circumstances that might disrupt the synchronization between embryo and endometrium have been suggested. Insufficient endometrium thickness, elevated progesterone levels and the presence of an LH surge are suggested disruptors of endometrium – embryo synchronization. Even though these circumstances are often observed during natural cycle frozen-thawed embryo transfer they seem to have little consequences with regard to pregnancy rates. Extensive hormonal monitoring also does not help identifying patients that will conceive from those that do not. From an efficiency point of view refraining from monitoring of various hormonal measurements and of the endometrial thickness can be considered

The predictive value of ovarian reserve tests for spontaneous pregnancy in subfertile ovulatory women

BACKGROUND: The predictive value of ovarian reserve tests (ORTs) for spontaneous pregnancy is unclear. Our study aimed to determine whether ORTs have added value to previously identified prognostic factors for spontaneous pregnancy in subfertile ovulatory couples. METHODS: A prospective cohort study was performed on 474 subfertile ovulatory couples in two hospitals in Groningen, The Netherlands. The ORTs performed were: antral follicle count (AFC), follicle-stimulating hormone (FSH), inhibin B (basal levels and after stimulation with clomiphene citrate) and the clomiphene citrate challenge test. For each couple, the probability of spontaneous pregnancy was retrospectively calculated using the validated Hunault prediction model which includes the main known prognostic factors for spontaneous pregnancy. Outcome measure was time to spontaneous pregnancy resulting in a live birth. RESULTS: When added to the Hunault model, only basal FSH and AFC significantly improved the prediction of spontaneous pregnancy (P-values of 0.05 and 0.04). Absolute changes in predicted probabilities after adding basal FSH or AFC were small: the predicted probability of spontaneous pregnancy shifted >or=10% in only 3.8% and 7.9% of the couples, respectively. CONCLUSIONS: Although basal FSH and AFC significantly improved the validated prediction model for spontaneous pregnancy, the clinical relevance of this finding is limited. We recommend that none of the ORTs studied should be used routinely in the subfertility evaluation of ovulatory couples to predict spontaneous pregnancy chances

Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH)

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Expectant management versus IUI in unexplained subfertility and a poor pregnancy prognosis (EXIUI study): a randomized controlled trial

STUDY QUESTION: For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in terms of live births?SUMMARY ANSWER: In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of EM is inferior compared to IUI-OS in terms of live births.WHAT IS KNOWN ALREADY: Couples with unexplained subfertility and a poor prognosis are often treated with IUI-OS. In couples with unexplained subfertility and a relatively good prognosis for natural conception (>30% in 12 months), IUI-OS does not increase the live birth rate as compared to 6 months of EM. However, in couples with a poor prognosis for natural conception (<30% in 12 months), the effectiveness of IUI-OS is uncertain.STUDY DESIGN, SIZE, DURATION: We performed a non-inferiority multicentre randomized controlled trial within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We intended to include 1091 couples within 3 years. The couples were allocated in a 1:1 ratio to 6 months EM or 6 months IUI-OS with either clomiphene citrate or gonadotrophins.PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied heterosexual couples with unexplained subfertility and a poor prognosis for natural conception (<30% in 12 months). The primary outcome was ongoing pregnancy leading to a live birth. Non-inferiority would be shown if the lower limit of the one-sided 90% risk difference (RD) CI was less than minus 7% compared to an expected live birth rate of 30% following IUI-OS. We calculated RD, relative risks (RRs) with 90% CI and a corresponding hazard rate for live birth over time based on intention-to-treat and per-protocol (PP) analysis.MAIN RESULTS AND THE ROLE OF CHANCE: Between October 2016 and September 2020, we allocated 92 couples to EM and 86 to IUI-OS. The trial was halted pre-maturely owing to slow inclusion. Mean female age was 34 years, median duration of subfertility was 21 months. Couples allocated to EM had a lower live birth rate than couples allocated to IUI-OS (12/92 (13%) in the EM group versus 28/86 (33%) in the IUI-OS group; RR 0.40 90% CI 0.24 to 0.67). This corresponds to an absolute RD of minus 20%; 90% CI: -30% to -9%. The hazard ratio for live birth over time was 0.36 (95% CI 0.18 to 0.70). In the PP analysis, live births rates were 8 of 70 women (11%) in the EM group versus 26 of 73 women (36%) in the IUI-OS group (RR 0.32, 90% CI 0.18 to 0.59; RD -24%, 90% CI -36% to -13%) in line with inferiority of EM.LIMITATIONS, REASONS FOR CAUTION: Our trial did not reach the planned sample size, therefore the results are limited by the number of participants.WIDER IMPLICATIONS OF THE FINDINGS: This study confirms the results of a previous trial that in couples with unexplained subfertility and a poor prognosis for natural conception, EM is inferior to IUI-OS

Expectant management versus IUI in unexplained subfertility and a poor pregnancy prognosis (EXIUI study): a randomized controlled trial

STUDY QUESTION: For couples with unexplained subfertility and a poor prognosis for natural conception, is 6 months expectant management (EM) inferior to IUI with ovarian stimulation (IUI-OS), in terms of live births?SUMMARY ANSWER: In couples with unexplained subfertility and a poor prognosis for natural conception, 6 months of EM is inferior compared to IUI-OS in terms of live births.WHAT IS KNOWN ALREADY: Couples with unexplained subfertility and a poor prognosis are often treated with IUI-OS. In couples with unexplained subfertility and a relatively good prognosis for natural conception (>30% in 12 months), IUI-OS does not increase the live birth rate as compared to 6 months of EM. However, in couples with a poor prognosis for natural conception (<30% in 12 months), the effectiveness of IUI-OS is uncertain.STUDY DESIGN, SIZE, DURATION: We performed a non-inferiority multicentre randomized controlled trial within the infrastructure of the Dutch Consortium for Healthcare Evaluation and Research in Obstetrics and Gynaecology. We intended to include 1091 couples within 3 years. The couples were allocated in a 1:1 ratio to 6 months EM or 6 months IUI-OS with either clomiphene citrate or gonadotrophins.PARTICIPANTS/MATERIALS, SETTING, METHODS: We studied heterosexual couples with unexplained subfertility and a poor prognosis for natural conception (<30% in 12 months). The primary outcome was ongoing pregnancy leading to a live birth. Non-inferiority would be shown if the lower limit of the one-sided 90% risk difference (RD) CI was less than minus 7% compared to an expected live birth rate of 30% following IUI-OS. We calculated RD, relative risks (RRs) with 90% CI and a corresponding hazard rate for live birth over time based on intention-to-treat and per-protocol (PP) analysis.MAIN RESULTS AND THE ROLE OF CHANCE: Between October 2016 and September 2020, we allocated 92 couples to EM and 86 to IUI-OS. The trial was halted pre-maturely owing to slow inclusion. Mean female age was 34 years, median duration of subfertility was 21 months. Couples allocated to EM had a lower live birth rate than couples allocated to IUI-OS (12/92 (13%) in the EM group versus 28/86 (33%) in the IUI-OS group; RR 0.40 90% CI 0.24 to 0.67). This corresponds to an absolute RD of minus 20%; 90% CI: -30% to -9%. The hazard ratio for live birth over time was 0.36 (95% CI 0.18 to 0.70). In the PP analysis, live births rates were 8 of 70 women (11%) in the EM group versus 26 of 73 women (36%) in the IUI-OS group (RR 0.32, 90% CI 0.18 to 0.59; RD -24%, 90% CI -36% to -13%) in line with inferiority of EM.LIMITATIONS, REASONS FOR CAUTION: Our trial did not reach the planned sample size, therefore the results are limited by the number of participants.WIDER IMPLICATIONS OF THE FINDINGS: This study confirms the results of a previous trial that in couples with unexplained subfertility and a poor prognosis for natural conception, EM is inferior to IUI-OS