O-166 A smartphone video clip on the patient journey to reduce patient’s anxiety: a randomized controlled trial

Study question Can a smartphone video clip detailing the patient journey decrease the anxiety of women and men on the day of their first oocyte aspiration? Summary answer The video clip does not affect the anxiety of women but does reduce the anxiety of men on the day of couples’ first oocyte aspiration. What is known already Infertility and in vitro fertilisation (IVF) decrease the personal wellbeing of women and men. Couples shared that this contributed to their IVF discontinuation despite a good prognosis and reimbursement of IVF. Previous longitudinal studies confirmed that pre-IVF anxiety is associated with IVF discontinuation. Limiting treatment anxiety is, therefore, relevant for fertility patients and clinics. Studies from the field of reproductive medicine examining the effect of preparatory information on anxiety suggest that focussed interventions seem more effective than complex interventions. Several randomized controlled trials (RCTs) found that preparatory information movies reduce anxiety for out-patient cardiology procedures in women and men. Study design, size, duration This monocentric RCT randomized (1:1 allocation; computerized) 190 heterosexual couples about to start their first IVF cycle between care as usual (i.e. preparatory information session 1-3 months before IVF) and care as usual combined with a novel intervention during a 24 months recruitment period (2018-2020). The novel intervention is a 5-minute smartphone video clip detailing the patient journey on the day of oocyte aspiration, which was sent to both partners the day before oocyte aspiration. Participants/materials, setting, methods Upon arrival at a private fertility clinic for their first oocyte aspiration women and men independently filled out the ‘STAI-State anxiety inventory’ and the ‘infertility distress scale (IDS)’ and evaluated the novel intervention, if applicable. A minority of randomized couples didn’t comply with the standard IVF trajectory (n = 27) or didn’t fill out the questionnaires (n = 8). The data of 155 couples (76-79/group, a-priori sample size calculation requested minimally 76/group) was subjected to a modified intention-to-treat analysis. Main results and the role of chance Women and men were on average 33 and 35 years old, respectively. Couples had a mean duration of infertility of 27 months and 63 of them (41%) had tried intrauterine insemination. The background variables were equally distributed between the intervention (IG) and control group (CG). The video clip did not affect women’s anxiety on the day of oocyte aspiration (mean STAI-State score IG 42.7±8.1 vs CG 42.1±8.5, p = 0.67). However, men who watched the video clip were significantly less anxious than men who did not watch it (mean STAI-State score IG 35.8±6.4 vs CG 38.2±7.6, p = 0.04). Surprisingly, infertility-specific distress was higher among women and men who watched the video clip (mean IDS scores of 25.8±4.9 and 22.6±5.0, respectively), as compared to women (p = 0.05) and men (p = 0.02) who did not watch the video clip (mean IDS score 24.3±4.6 and 20.8±4.7, respectively). All women and men of the intervention group, except one woman, would recommend the video clip to friends and family going through IVF. The intervention and control group did not differ significantly regarding clinical pregnancy rate (31/76 vs. 29/79, p = 0.60) or miscarriage rate (2/76 vs. 3/79, p = 0.68) 12 weeks after their first oocyte aspiration. Limitations, reasons for caution Patients nor assessors were blinded and there was no attention control group. Selection bias is plausible although the participation rate was 89%. Assessing infertility-specific distress the day after watching the video clip was not optimal, as priming couples to feel infertility-specific distress short term is less problematic than longer term. Wider implications of the findings Providing additional procedural information is interesting for clinics as patients recommended the video clip and as it decreased men’s anxiety. A follow-up study should examine whether the video clip’s priming effect on infertility-specific distress lasts longer than only the day after and whether the video clip affects IVF discontinuation. Trial registration number NCT03717805

P–767 Cumulative live birth rate after IVF - trend over time and the impact of blastocyst culture and vitrification

Study question Has cumulative live birth rate (CLBR) improved over time and which factors are associated with such an improvement? Summary answer During 2007–2017, CLBR per oocyte aspiration increased significantly (27.0% to 36.3%), in parallel with an increase in blastocyst transfer and cryopreservation by vitrification. What is known already While it has been shown that live birth rate (LBR) per embryo transfer (ET) is higher for fresh blastocyst than for fresh cleavage stage embryo transfer, CLBR per oocyte aspiration, including one fresh ET and all subsequent frozen embryo transfers (FET), does not seem to differ between the two culture strategies. Study design, size, duration STUDY DESIGN, SIZE, DURATION: National register study including all oocyte aspirations performed in Sweden 2007–2017, n = 124 700. Donation cycles excluded. Participants/materials, setting, methods Data were retrieved from the Swedish National Registry of Assisted Reproduction (Q-IVF). CLBR was defined as the number of deliveries with at least one live birth resulting from one oocyte aspiration, including all fresh and/or frozen embryo transfers within one year. The delivery of a singleton, twin, or other multiples was registered as one delivery. Cryopreservation of cleavage stage embryos was performed by slow freezing and of blastocyst by vitrification. Main results and the role of chance Overall, the CLBR per oocyte aspiration increased significantly during the study period, from 27.0% to 36.3% (OR 1.039, 95% CI 1.035–1.043) and from 30.0% to 43.3% if at least one ET was performed (AOR 1.055, 95% CI 1.050–1.059). The increase in CLBR was independent of maternal age, number of oocytes retrieved and number of previous IVF live births. The CLBR for women <35 years and ≥ 35 years both increased significantly, following the same pattern. During the study period a substantially increasing number of blastocyst transfers were performed, both in fresh and in FET cycles. An important contributor included in the blastocyst strategy, may be the extended culture of the total cohort of embryos, also embryos earlier discarded at early cleavage stages, in order to reach the blastocyst stage. These embryos may contribute to the total number of available blastocysts and thereby increase the chance of a live birth within that oocyte aspiration cycle. Other important predicting factors for live birth, such as number of embryos transferred, could not explain the improvement, on the contrary the single embryo transfer (SET) rate increased with time. Limitations, reasons for caution The retrospective design implicates that other confounders of importance for CLBR can not be ruled out. In addition, some FET cycles might be performed later than one year post oocyte aspiration for the last year (2017) and are thus not included in this study. Wider implications of the findings: The results suggest that blastocyst transfer, particularly when used in FET cycles and in combination with vitrification, is an important contributor to the improved live birth rates over time. This gives a possibility for fewer oocyte aspirations needed to achieve a live birth and a shortened time to live birth. Trial registration number -

P-767 Cumulative live birth rate after IVF - trend over time and the impact of blastocyst culture and vitrification

Study question Has cumulative live birth rate (CLBR) improved over time and which factors are associated with such an improvement? Summary answer During 2007-2017, CLBR per oocyte aspiration increased significantly (27.0 % to 36.3 %), in parallel with an increase in blastocyst transfer and cryopreservation by vitrification. What is known already While it has been shown that live birth rate (LBR) per embryo transfer (ET) is higher for fresh blastocyst than for fresh cleavage stage embryo transfer, CLBR per oocyte aspiration, including one fresh ET and all subsequent frozen embryo transfers (FET), does not seem to differ between the two culture strategies. Study design, size, duration STUDY DESIGN, SIZE, DURATION: National register study including all oocyte aspirations performed in Sweden 2007-2017, n = 124 700. Donation cycles excluded. Participants/materials, setting, methods Data were retrieved from the Swedish National Registry of Assisted Reproduction (Q-IVF). CLBR was defined as the number of deliveries with at least one live birth resulting from one oocyte aspiration, including all fresh and/or frozen embryo transfers within one year. The delivery of a singleton, twin, or other multiples was registered as one delivery. Cryopreservation of cleavage stage embryos was performed by slow freezing and of blastocyst by vitrification. Main results and the role of chance Overall, the CLBR per oocyte aspiration increased significantly during the study period, from 27.0 % to 36.3 % (OR 1.039, 95% CI 1.035-1.043) and from 30.0 % to 43.3 % if at least one ET was performed (AOR 1.055, 95% CI 1.050-1.059). The increase in CLBR was independent of maternal age, number of oocytes retrieved and number of previous IVF live births. The CLBR for women < 35 years and ≥ 35 years both increased significantly, following the same pattern. During the study period a substantially increasing number of blastocyst transfers were performed, both in fresh and in FET cycles. An important contributor included in the blastocyst strategy, may be the extended culture of the total cohort of embryos, also embryos earlier discarded at early cleavage stages, in order to reach the blastocyst stage. These embryos may contribute to the total number of available blastocysts and thereby increase the chance of a live birth within that oocyte aspiration cycle. Other important predicting factors for live birth, such as number of embryos transferred, could not explain the improvement, on the contrary the single embryo transfer (SET) rate increased with time. Limitations, reasons for caution The retrospective design implicates that other confounders of importance for CLBR can not be ruled out. In addition, some FET cycles might be performed later than one year post oocyte aspiration for the last year (2017) and are thus not included in this study. Wider implications of the findings The results suggest that blastocyst transfer, particularly when used in FET cycles and in combination with vitrification, is an important contributor to the improved live birth rates over time. This gives a possibility for fewer oocyte aspirations needed to achieve a live birth and a shortened time to live birth. Trial registration number -

Why do women choose to undergo oocyte aspiration without sedation or analgesia?

Objective Oocyte pick-up (OPU) is a painful but essential part of in-vitro fertilization (IVF) that is usually performed under sedation and analgesia (SaA). Our aim was to study that why some women decide to undergo OPU without SaA? Methods This was a prospective study using patient questionnaires and the standardized 7-item generalized anxiety disorder (GAD-7) score. The patients were asked to assess the pain experienced during OPU using a visual analog scale (VAS). The study sample was a convenience sample of 100 healthy women undergoing OPU at our unit with or without SaA. Results Women who chose to undergo OPU without SaA were significantly more likely to express the fear of anesthesia. A high pain score (VAS ≥ 6) was reported by significantly more patients who underwent OPU without SaA than with SaA. Yet, 98% of the patients who underwent OPU without SaA stated that in future IVF cycles, they would still choose to undergo OPU without SaA. More patients had high anxiety scores among those who underwent OPU with than without SaA. Conclusions Women who chose to undergo OPU without SaA reported more often fear of anesthesia. Although these women experienced significantly more pain during OPU, almost all of them suggested that they would still choose to undergo OPU without SaA. Increased anxiety, as expressed by higher GAD-7 scores, was not associated with a tendency to choose SaA during OPU. The option of OPU without SaA seems to be an acceptable option for selected women. Lay summary Egg retrieval from the ovaries is a painful part of in vitro fertilization (IVF). It is, therefore, usually performed under sedation and pain relief (analgesia). The aim of this study was to investigate: Why some women decide to undergo egg retrieval without sedation? We prospectively studied 100 women using patient questionnaires and standardized scores in order to measure patient's pain and anxiety levels. We found that women who chose to undergo egg retrieval without sedation were significantly more likely to express fear of anesthesia. As expected, women who decided to forgo sedation experienced more pain during egg retrieval, yet, 98% of them decided that in future IVF cycles, they would still choose to undergo egg retrieval without sedation. Surprisingly, women who had high anxiety scores were not more likely to ask for sedation during egg retrieval. The option to undergo egg retrieval without sedation during IVF seems to be acceptable for some women.

Metabolomics analysis of follicular fluid coupled with oocyte aspiration reveals importance of glucocorticoids in primate periovulatory follicle competency

Gonadotropin administration during infertility treatment stimulates the growth and development of multiple ovarian follicles, yielding heterogeneous oocytes with variable capacity for fertilization, cleavage, and blastocyst formation. To determine how the intrafollicular environment affects oocyte competency, 74 individual rhesus macaque follicles were aspirated and the corresponding oocytes classified as failed to cleave, cleaved but arrested prior to blastulation, or those that formed blastocysts following in vitro fertilization. Metabolomics analysis of the follicular fluid (FF) identified 60 unique metabolites that were significantly different between embryo classifications, of which a notable increase in the intrafollicular ratio of cortisol to cortisone was observed in the blastocyst group. Immunolocalization of the glucocorticoid receptor (GR, NR3C1) revealed translocation from the cytoplasm to nucleus with oocyte maturation in vitro and, correlation to intrafollicular expression of the 11-hydroxy steroid dehydrogenases that interconvert these glucocorticoids was detected upon an ovulatory stimulus in vivo. While NR3C1 knockdown in oocytes had no effect on their maturation or fertilization, expansion of the associated cumulus granulosa cells was inhibited. Our findings indicate an important role for NR3C1 in the regulation of follicular processes via paracrine signaling. Further studies are required to define the means through which the FF cortisol:cortisone ratio determines oocyte competency.

124 Effect of transvaginal oocyte aspiration on equine blood and peritoneal fluid parameters

Transvaginal aspiration of oocytes (TVA) in the equine industry has gained more relevance and become a valuable technique to produce offspring from subfertile mares. TVA is a semi-invasive procedure and requires handling the ovaries transrectally to position them closely to an ultrasound probe located in the mare’s vagina. Once the ovary lies in close apposition to the ultrasound probe, a 12G needle is inserted through the needle guide, puncturing, aspirating, and scraping each follicle to recover the oocyte. Potential complications described include rectal tears, puncturing of blood vessels, ovarian abscesses, and peritonitis. Occasionally, problems occur after uneventful procedures, such as colic, peritonitis, pain, and anorexia. However, the source of these complications is not fully known. We hypothesize that blood and peritoneal fluid parameters would differ pre- and post-TVA in mares. A few reports provide some parameters after TVA (e.g. peritoneal protein, neutrophils, nucleated cells) without reference to pre-TVA values. These studies have not identified an effect in peritoneal fluid variables due to multiple abdominocenteses. Therefore, our aim was to analyse blood and peritoneal fluid in mares pre- and post-TVA, and to identify changes in parameters of the procedure (duration, number of pokes, number of follicles) and the mares’ clinical responses. Ten healthy mares were selected to undergo the procedure. Thirty minutes before starting TVA, a blood sample was drawn for complete blood count (CBC) and blood chemistry, and abdominocentesis was performed to obtain abdominal fluid and assess the cytology. This same protocol was repeated 24 hours after TVA. Physical exams were performed pre- and post-TVA. Paired t-tests were used to identify differences between groups (pre- and post-TVA). Spearman correlations (ρ) were used to assess the relationship between variables. There was a significant increase in peritoneal lactate (5.65-fold), peritoneal total protein (2.4-fold), and total nucleated cells (46-fold) between pre- and post-samples. These parameters were not associated with operator, number of times the needle was introduced into the ovaries, or number of aspirated follicles. The remaining parameters evaluated in CBC and blood chemistry did not differ. A positive correlation between total peritoneal protein and blood albumin was found post-TVA (ρ=0.72, P=0.01) but not pre-TVA (ρ=−0.1, P=0.65), suggesting an increase in protein level due to bleeding. Clinically, 9 mares were healthy throughout the study except one that presented signs of pain (facial grimace, anorexia, hyperthermia) the day following TVA. In conclusion, we showed changes in the peritoneal fluid during uneventful TVA procedures. The information provided by this research gives further insight into changes potentially caused by a TVA in abdominal fluid parameters. Further studies are necessary to determine expected standards and the duration of the changes after TVA.

Pain Relief during Oocyte Retrieval by Transcutaneous Electrical Acupoint Stimulation: A Single-Blinded, Randomized, Controlled Multicenter Trial

Acupuncture has pain-relief effects, but no data were available on the use of transcutaneous electric acupoint stimulation (TEAS) in pain relief during oocyte retrieval. This study was designed to examine the effect of TEAS for pain relief in women undergoing transvaginal ultrasound-guided oocyte aspiration. This single-blinded, multicenter, randomized controlled trial was performed in China between May 2013 and May 2015. The subjects were randomized to mock TEAS and TEAS. TEAS or mock TEAS was administered 30 min before oocyte retrieval until the end of the operation. The primary and secondary endpoints were the pain measured using the visual analog scale (VAS) within 1 min and 1 hour after oocyte retrieval, respectively. Serum β-endorphin levels were tested in the first 50 patients/group. 390 women were undergoing oocyte retrieval. Pain levels evaluated using VAS within 1 min (18.6 ± 1.3 vs. 24.4 ± 1.7, P<0.01) and 1 h after oocyte aspiration (4.6 ± 0.7 vs. 6.8 ± 0.8, P<0.05) were lower in the TEAS group than in the mock TEAS group. Nausea assessment revealed a significantly lower VAS score in the TEAS group within 1 min (1.2 ± 0.4 vs. 2.9 ± 0.7, P<0.033). Serum β-endorphin levels were significantly higher in the TEAS group than in the mock TEAS group (11.4 ± 0.5 vs. 9.1 ± 0.4, P<0.001) after retrieval. Serum β-endorphin levels were higher in the TEAS group after the procedure than baseline (11.4 ± 0.5 vs. 9.1 ± 0.3, P<0.001). Oocyte retrieval causes pain and discomfort, but TEAS is effective and safe for suppressing the pain and alleviating nausea associated with the operation.

Gene Expression in Granulosa Cells From Small Antral Follicles From Women With or Without Polycystic Ovaries

Context Polycystic ovary syndrome (PCOS) is the most common cause of anovulation. A key feature of PCOS is arrest of follicles at the small- to medium-sized antral stage. Objective and Design To provide further insight into the mechanism of follicle arrest in PCOS, we profiled (i) gonadotropin receptors; (ii) characteristics of aberrant steroidogenesis; and (iii) expression of anti-Müllerian hormone (AMH) and its receptor in granulosa cells (GCs) from unstimulated, human small antral follicles (hSAFs) and from granulosa lutein cells (GLCs). Setting GCs from hSAFs were collected at the time of cryopreservation of ovarian tissue for fertility preservation and GLCs collected during oocyte aspiration before in vitro fertilization/intracytoplasmic sperm injection. Participants We collected hSAF GCs from 31 women (98 follicles): 10 with polycystic ovaries (PCO) and 21 without. GLCs were collected from 6 women with PCOS and 6 controls undergoing IVF. Main Outcome Measures Expression of the following genes: LHCGR, FSHR, AR, INSR, HSD3B2, CYP11A1, CYP19, STAR, AMH, AMHR2, FST, INHBA, INHBB in GCs and GLCs were compared between women with PCO and controls. Results GCs in hSAFs from women with PCO showed higher expression of LHCGR in a subset (20%) of follicles. Expression of FSHR (P < 0.05), AR (P < 0.05), and CYP11A1 (P < 0.05) was lower, and expression of CYP19A1 (P < 0.05), STAR (P < 0.05), HSD3B2 (P = NS), and INHBA (P < 0.05) was higher in PCO GCs. Gene expression in GL cells differed between women with and without PCOS but also differed from that in GCs. Conclusions Follicle arrest in PCO is characterized in GCs by differential regulation of key genes involved in follicle growth and function.