Pregnancy Rate In Group Research Articles

O-068 The BISTIM study: first RCT comparing dual ovarian stimulation on the same cycle (duostim) vs 2 conventional ovarian stimulations in poor ovarian responders undergoing IVF

Abstract Study question Is the number of cumulated oocytes with dual ovarian stimulation on the same cycle (duostim) higher compared to 2 consecutive antagonist cycles in poor responders? Summary answer Considering the number of total and mature oocytes collected in poor ovarian responders, there is no benefit of duostim vs two consecutive antagonist cycles. What is known already Several waves of follicular development exist on the same cycle. Recent studies have shown the ability to obtain oocytes with equivalent quality in the luteal phase, even after a previous ovarian stimulation in the follicular phase. During stimulation, smaller follicles are recruited and sensitized, which may increase the selection of follicles available on the second stimulation. In poor ovarian responders (POR) this potentialization may have a great interest, as 2 stimulations on the same cycle could give a higher number of oocytes compared to two conventional stimulations. However, these preliminary data need to be confirmed with a randomized controlled trial. Study design, size, duration This is a multicenter, open-labeled randomized control trial (2018, september – 2021, march). The primary objective was to demonstrate that two ovarian stimulations within the same cycle (first in the follicular phase, followed by a second in the luteal phase) lead to the retrevial of 1.5 more oocytes than the cumulative number of oocytes from two consecutive conventional stimulation, in POR women. According to this hypothesis, 44 patients were needed in each group. Participants/materials, setting, methods 88 POR women, defined with Bologna criteria (AFC≤5 and/or AMH≤1.2ng/ml and ≤3 oocytes if previous IVF) were randomized, 44 in duostim group (D) and 44 in conventional group (C). FertistartKit® 300IU/day with antagonist protocol was used except in luteal phase stimulation of group D. In group D, oocytes were pooled and inseminated after the second retrieval, with freeze all embryos. Fresh transfer was performed in group C. The analysis is presented in intention to treat. Main results and the role of chance There was no difference between the groups regarding demographics, ovarian reserve markers (AFC, AMH) and stimulation parameters. The mean number of cumulated oocytes retrieved with 2 ovarian stimulation was not statistically different in group D and C, respectively 5.0+/-3.4 and 4.6+/-3.4 (p = 0.56). The mean number of cumulated mature oocytes was not statistically different, 3.7+/-3.3 in group D vs 3.1+/-3.0 in group C (p = 0.38). The mean number of embryos was significantly lower in the group D, 0.8+/-1.3 vs group C 1.6+/-1.3 (p < 0.01). There was no statistical difference of the mean number of oocytes retrieved per cycle in cycle 1 vs cycle 2 in both group D and C. The delay, between the first and the second day 1 of stimulation was statistically different in group D 14.4 days (10-19) vs group C 90.6 (28-232). The ongoing pregnancy rate in group D 17.9% (7/39) was not statistically different with group C 29.3% (12/41), (p = 0.23). And the mean time to ongoing pregnancy tends to be longer in group D (144 days) vs group C (115 days) but was not statistically different (p = 0.21). Limitations, reasons for caution The RCT was impacted by Covid pandemia and stop of IVF activities for 10 weeks. Delays were recalculated to exclude this period, however one women in group D cannot have the luteal stimulation. We also faced unexpected good ovarian responses and pregnancies after the first oocyte pick-up in group C. Wider implications of the findings In routine practice, the benefit of duostim in patients with POR is not confirmed. Firstly, because there is no potentialization on the number of oocyte retrieved in luteal phase after follicular phase stimulation. Secondly, because the freeze all strategy avoids a pregnancy with fresh embryo transfer after the first cycle. Trial registration number 2017-A00498-45

P-138 Transcriptomic signatures in trophectoderm and inner cell mass of human blastocysts with expected pregnancy rates

Abstract Study question Is it possible to identify the molecular factors that contribute to the implantation potential of blastocysts? Summary answer Genes correlated with expected pregnancy rate in trophectoderm (TE) and inner cell mass (ICM) respectively were identified, and aneuploidy alone couldn’t predict the pregnancy expectation. What is known already The selection of suitable embryos for transfer is critical for achieving successful pregnancy outcomes in assisted reproductive technology (ART). Although pre-implantation genetic testing for aneuploidy (PGT-A) as well as morphological and chronological evaluation of embryos, have been conducted in clinical practice, they do not fully guarantee successful pregnancy. Recently, transcriptional events in early human embryonic development have been analyzed using RNA-sequencing (RNA-seq) and researchers are attempting to apply this information to ART. Study design, size, duration To determine the correlation between blastocyst evaluation and pregnancy rate, we retrospectively analyzed 1,890 cases underwent frozen-thawed blastocyst transfer from March 2018 to December 2020. A total of 13 blastocysts that were cryopreserved for clinical use between February 2011 and September 2018, then scheduled for disposal and with consented for research, were subjected to RNA-seq without distinguishing between conventional in vitro fertilization (c-IVF) and intracytoplasmic sperm injection (ICSI). Participants/materials, setting, methods Blastocysts were donated by infertile couples undergoing c-IVF or ICSI cycles at the Yamashita Shonan Yume Clinic with informed consent under ethical approval. TE and ICM cells were collected from blastocysts by using a micromanipulator and then subjected to RNA-seq. Gene expression analysis and digital karyotyping using RNA-seq were performed simultaneously for TE and ICM cells, respectively. One-way analysis of variance, chi-square test and Tukey's multiple comparison test were used for this study. Main results and the role of chance Blastocysts were classified into three groups to correlate with pregnancy rates based on the diameter of the blastocyst and the time to reach this size: those taking less than 130 h to reach a diameter of > 170 μm (Group 1, n = 676), those taking more than 140 h to reach a diameter of < 180 μm (Group 2, n = 158), and the rest (Group 3, n = 1,056). The pregnancy rates of Groups 1, 2 and 3 were 59.0%, 16.5%, and 34.2%, respectively (p < 0.01). Assessing the differences in overall transcripts correlated between Group 1 (n = 5), Group 2 (n = 4), and Group 3 (n = 4), 26 and 67 differentially expressed genes (DEGs) were identified in ICM and TE cells, respectively. Importantly, downregulated genes in TE of blastocysts with lower expectation of pregnancy included tight junction-related genes, such as CXADR, CLDN10, and ATP1B1, which were implicated in peri-implantation development. Digital karyotyping revealed karyotypic abnormalities and mosaicism in all groups with no common abnormalities observed, suggesting that aneuploidy alone cannot predict the pregnancy expectation. Limitations, reasons for caution Although 93 genes potentially related to implantation have been identified, it is still unclear how these genes are involved in implantation. In vitro implantation models using human embryos and artificial embryos currently under development are expected to contribute to the elucidation of the functions of these genes. Wider implications of the findings Our results provide reliable candidates for genes that could allow for non-invasive selection of high-quality blastocysts for ART and add to the knowledge base of transcriptional events in human peri-implantation development. Trial registration number not applicable

Subcutaneous progesterone (Prolutex) versus vaginal (Cyclogest) for luteal phase support in IVF/ICSI cycles: a randomized controlled clinical trial

BackgroundTo compare the safety, efficacy, and tolerability of subcutaneous vaginal progesterone suppository for luteal phase support (LPS) in assisted reproduction technology (ART) cycles in patients referred to the Royan Institute.MethodsThis randomized clinical trial was conducted from August 2016 to March 2018. The infertile patients undergoing in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) were evaluated. The controlled ovarian stimulation (COH) was performed in all of the patients with standard long GnRH agonist protocol. After ovum pickup, eligible women were randomly allocated into two groups. In group A, since oocyte retrieval day, subcutaneous injections of progesterone (50 mg) (Prolutex®) were used daily, and in group B, two vaginal suppositories (Cyclogest ®) were administrated for LPS. The clinical pregnancy and miscarriage rates and the drug’s side effect were compared between two groups by appropriate statistical tests.ResultsFinally, 40 patients in each group were enrolled, and the IVF/ICSI outcomes were compared between groups. The data analysis showed that no significant differences were found between groups in terms of the demographic, infertility characteristics, and the COH outcome between groups. The chemical and clinical pregnancy rates (CPR) in group A were significantly higher than those of group B (P = 0.04, P = 0.02, respectively). The implantation and twin pregnancy rates in group B were significantly higher than those in group A (P = 0.009, P = 0.02, respectively).ConclusionThe subcutaneous administration of progesterone 25 mg twice daily for LPS was associated with higher CPR versus vaginal progesterone, and it was safe and well-tolerated in the follow-up. In addition, it can be a suitable replacement in cases of allergic reactions to vaginal suppositories. However, further study is required to compare the cost-effectiveness of these medications.Trial registrationThe study was also registered in the Iranian Registry of Clinical Trials on February 19, 2015 (IRCT201402191141N18 at www.irct.ir, registered prospectively).

Improvement of bovine pregnancy rate through intravaginal biostimulation with penis like device

The aim of this study was to increase bovine pregnancy rate by intra-vaginal biostimulation penis like device (PLD). A total of 336 heifers/cows were AI, in which PLD was used in 193 animals. Animals were grouped as A (only AI) and B (PLD after AI). The overall pregnancy rate was 70.0%. Pregnancy rate in group B was significantly (P=0.004) higher than that of group A. Cows of >7.5 years old is showed lower pregnancy rate in group A, but higher in group B. The heifers were showed more responsive to PLD than others parity. The parity 5 or more in group B was responded to PLD and showed higher pregnancy rate than that of group A. It was found that age was significantly positive correlation parity whereas significantly negative correlation with breed. It is concluded that PLD will increased the pregnancy rate of cows through biostimulation on vagina.
 Bangladesh J. Sci. Ind. Res. 57(2), 101-108, 2022

Influence of hormonal synchronization protocols in heifers-recipients on their pregnancy rate with the use of frozen-thawed embryos

At the moment, there are a great number of protocols enabling to prepare recipients for embryo transfer. However, because of their effectiveness variety on cattle breeding farms the issue of searching of practical schemes that allow successful reproductive cycle synchronization in recipients with the achievement of their highest pregnancy rate becomes relevant. Based on the information above, the aim of the study was to determine the most effective estrous cycle synchronization protocol in recipient heifers before embryo transfer which provide the high level of their pregnancy rate with the use of frozen-thawed embryos. The research was carried out on the beef cattle in Samara region of Russia. In the course of the study, the heifers (n=107) were selected as the potential recipients and then divided into three groups depending on the applied protocol for the estrous cycle synchronization. All the recipients were transferred with frozen-thawed embryos obtained in vivo from Aberdeen Angus donor cows. The doses of the drug products indicated below were administrated per one animal. During the study, it was found that in group I where we used a protocol included a double administration of 2 ml of the drug "Oestrophan" (Czech Republic) with an interval of 11 days estrous cycles were synchronized in 72.73±0.80 percent of animals. The pregnancy rate in group I was 29.17±0.97 percent. In group II where we applied a protocol included a double administration of "Surfagon" (Russia) at a dose of 10 ml and Oestrophan with an interval of 11 days estrous cycles were synchronized in 50.0±0.86 percent of animals. The pregnancy rate in that group was 61.11±1.22 percent. In group III that included the application of intravaginal progesterone implant CIDR with a simultaneous administration of Surfagon at a dose of 2 ml and at the time of CIDR extraction the administration of 2 ml of Oestrophan, estrous cycles were synchronized in 63.16±0.80 percent of animals. The pregnancy rate in that group was 66.67±1.00 percent. Thus, the group III was characterized by the highest pregnancy rate that was achieved by the application of the protocol included intravaginal progesterone implant CIDR in combination with both medical products Surfagon and Oestrophan.

Impact of growth hormone supplementation on improving oocyte competence in unexplained poor embryonic development patients of various ages

Objectives To evaluate the effectiveness of Growth hormone (GH) co-treatment during in vitro fertilization (IVF) cycles in women of different ages who manifest unexplained poor embryonic development. Method This cohort study included a total of 2647 patients with unexplained poor embryonic development in their previous IVF procedures: 872 women received GH co-treatment and 1775 untreated women served as a control group. Patients were divided into 6 groups according to treatment and stratified by age (<35 years of age, A-GH group and A-control group; 35–40 years, B-GH group and B-control group; and ≥40 years, C-GH group and C-control group). The primary outcome was the oocyte-cleavage rate and the clinical pregnancy rate (CPR). Results The oocyte-cleavage rates among the three age groups were significantly higher in the GH group compared to the same-aged control group. In both group A and group B, there was no significant difference in clinical pregnancy rate between the GH group and controls. However, in patients ≥40 years of age, the clinical pregnancy rate in the GH group was significantly higher than in the control group (31.8% vs. 13.7%, p = 0.019). In the three age groups, there was no significant difference in the live birth rate between the GH group and controls. In the multivariate logistic regression analysis model, in both group A and group B, the number of cleaved embryos was independent predictors for CPR (OR = 1.464, 95% CI: 1.311–1.634; respectively, OR = 1.336, 95% CI: 1.126–1.586); Besides, in both group B and group C, age was independent predictors for CPR (OR = 0.657, 95%CI: 0.555–0.778; respectively, OR = 0.622, 95%CI: 0.391–0.989). However, only in group C, supplementation GH increased CPR as compared with not supplementation GH (OR = 2.339, 95%CI: 1.182–6.670). Conclusions For patients with unexplained poor embryonic development, supplementation with GH increased the oocyte-cleavage rates in all three age groups, and the clinical pregnancy rate gradually improved commensurate with increasing age. There was no difference in the clinical pregnancy rate in group A and group B, but group C improved significantly. Therefore, compared with patients under 40 years of age, patients ≥40 may benefit more from GH supplementation.

INFLUENCE OF SPERM PARAMETERS ON INCIDENCE OF PREGNANCY BY INTRAUTERINE INSEMINATION

The main aim of this study was to identify whether different sperm parameters influence the rate of pregnancies in couples suffering from mild to moderate infertility issues after treatment through IUI. Retrospective Statistical study was done from data of IUI where 450 sub fertile and infertile couples with normal ovulation and tubal patency under age 30 underwent for IUI. Sperm parameters were evaluated before and after preparation. The impact of the sperm characteristics on pregnancy rates after IUI was evaluated. Male Patients semen was divided into four groups Group 1 –Normozoospermia(G1 -116) Group 2- Asthenozoospermia (Progressive motility included in this study-< 32% G2--109) Group 3- Teratozoospermia(morpholology-included in this study < 4% G3-111) and Group 4- Asthenoteratozoospermia(G4 -114) in all four groups concentration, Motility and Morphology parameters is taken according to WHO guidelines . Pregnancy is confirmed with presence of fetal heart beat in ultrasound scan. Effect of Semen characters like Concentration, Motility and Morphology were checked individually or combined and pregnancy outcomes were evaluated. Retrospectively, the data of 450 patients were examined. The median age of patients performing the insemination was 28.7 years (minimum 22 years, maximum 30 years). Pregnancy rate was 14.65% [ 17/116] in group-1, whereas pregnancy rate for group- 2 ,3 and 4 were 13.76% [15/109], 12.61% [14/111] and 12.28% [ 14/114] respectively. Reduced pregnancy rate was seen in Teratozoospermia and Asthenoteratozoospermia but statistically no significance proven Semen parameter is an important predictor for the outcome of IUI. Sperm concentration, motility, morphology, and the number of motile spermatozoa inseminated determine the successful pregnancy rate. But which semen parameter is good predictor for successful pregnancy is still a question.

PREDICTIVE VALUE OF THE NUMBER OF FROZEN BLASTOCYSTS IN LIVE BIRTH RATES OF THE TRANSFERRED FRESH EMBRYOS

Blastocyst development by extended culture in vitro allows the embryos to ‘select’ themselves, thus successful growth to the blastocyst stage is a reflection of the developmental competence of cleavage stage embryos in a cohort. The study aims to determine whether the number of frozen blastocysts is associated with live birth rates of the transferred fresh embryos. The retrospective study included 8676 cycles of first fresh embryo transfer from January 2016 to June 2019 at a fertility center of a university hospital. The patients with ≥10 oocytes retrieved were divided into three groups according to the number of frozen blastocysts: 0 (group 1), 1-2 (group 2), and ≥3 (group 3).The primary outcome measure was the live birth. The secondary outcome measures included clinical pregnancy rates and implantation rates. Logistic regression analysis was also performed. Live birth rates in patients with ≥3 and 1-2 frozen blastocysts were 47.6% and 46.1%, respectively, which were significantly higher than that in patients without blastocyst (36.0%). The clinical pregnancy rate in group 3 was 65.1%, which was also significantly higher than the other two groups (47.0% and 59.2%). The implantation rates were 35.5%, 47.6%, and 56.0% in the three groups, respectively, P = 0.000. Compared with groups of frozen blastocysts, 0 frozen blastocyst yielded a lower rate of live birth (the adjusted ORs: 0.526, 95% CI: 0.469, 0.612). In patients with optimal ovarian response, fresh embryos transfer followed by having blastocysts frozen is a strong indicator of pregnancy achievement, but the number of frozen blastocysts (if not = 0) has limited value in predicting live birth rates.

P–249 Does the re-expansion of thawed embryos affect the clinical outcomes of human blastocyst vitrification?

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 &amp;lt; 0.05). The number of good quality blastocyst transferred in group 1 was higher than in group 2 (p &amp;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

P–635 Standard versus mild ovarian stimulation in women with polycystic ovaries (PCO): Impact on outcomes in subsequent frozen embryo treatment cycles (FET)

Abstract Study question Does mild ovarian stimulation in women with PCO result in higher live birth rates during subsequent FET cycles? Summary answer Mild ovarian stimulation with FSH doses &amp;lt;150IU did not result in higher clinical pregnancy or livebirth rates in subsequent FET. What is known already Ovarian stimulation during IVF in women with PCO is associated with an exaggerated response, ovarian hyperstimulation syndrome, poor egg to follicle ratio, low fertilisation rates and poor blastocyst conversion. Mild ovarian stimulation, often referred to as protocols with FSH doses under 150IU, is often employed to overcome these challenges. One of the perceived benefits of this approach is improved oocyte and embryo quality reflected in lower aneuploidy rates. Study design, size, duration This was a retrospective observational study looking at 99 FET between January 2011 and Jan 2021 that followed a fresh cycle in women with a pre-treatment antral follicle count of 12 + 12 or greater. Patients were identified through the antral follicle count at the pre-treatment investigation ultrasound scan. Ultrasound findings, treatment cycle details and clinical outcomes were entered prospectively into a dedicated clinic database. Data was retrieved and analysed using SPSS V25. Participants/materials, setting, methods The study was conducted in a large IVF centre. Data on women with an AFC of 12 + 12 or above, undergoing an autologous FET cycle following a fresh cycle were collected. Women were split into those receiving &amp;lt;150IU of FSH (Group1, n = 51) and those receiving FSH ³150 IU (Group 2, n = 48). Binary logistic regression analysis was performed to control for confounders. Live birth was the primary outcome, with biochemical and clinical pregnancy being secondary outcomes. Main results and the role of chance Women in Group 1 were younger (30.8±3.6 v 33.8±3.65, p &amp;lt; 0.005) but had a similar antral follicle count (38.2±11.7 v 34.2±9.1, p = 0.07). The total number of eggs collected (24.1±13.8 v 25.9±8.8, p = 0.45) and fertilisation rate (0.59±0.2 v 0.58±0.18, p = 0.77) during their fresh cycle were comparable. Women in Group 2 had a larger number of embryos suitable for cryopreservation (7.36±4.2 v 4.8±3.5, p = 0.001) In the subsequent frozen embryo replacement cycle, there was no difference in the number or quality of embryos transferred with most women having a single embryo transfer (63% v 48%, p = 0.14) and at least one top quality embryo transferred (68.6% v 81%, p = 0.15). There was a higher biochemical pregnancy rate in Group 1 (84% v 66%, p = 0.035) but with no difference in clinical pregnancy rate (53% v 44%, p = 0.37) or live birth rate (49% v 42%, p = 0.76). Live birth rates remained comparable even after controlling for age, and number and quality of embryos transferred (OR: 1.21 (95% CI 0.50–2.94). Limitations, reasons for caution This was a retrospective analysis raising the risk of allocation bias. This study was also at risk of information bias as it relied on accurate documentation of the AFC at the pre-treatment scan. Wider implications of the findings: Patients can be reassured that both stimulation protocols result in similar live birth rates in subsequent frozen embryo replacement cycles. Prospective trials using PGT-A are required to assess whether aneuploidy could account for the discrepancy in biochemical pregnancy rates in the two groups considering the subsequent comparable clinical pregnancy rates. Trial registration number Not applicable

P–605 Low serum progesterone on the day of frozen embryo transfer after artificial endometrial preparation: exploring the clinical impact of “rescue” strategies

Abstract Study question Can we rescue treatments with low progesterone (PG) levels the day of frozen embryo transfer (FET) by adding subcutaneous progesterone? Summary answer After receiving additional supplementation with subcutaneous progesterone, women with low serum progesterone on cryotransfer day, have similar ongoing pregnancy rates as women with normal levels. What is known already Micronized vaginal progesterone fails to achieve optimal serum levels in up to 30% of patients receiving frozen embryos under artificial cycles (AC) despite the administration of 400 mg twice daily. Cancelling the thawing process and restarting a new treatment is a very disappointing option for patients and doctors. An alternative strategy is to administrate additional progesterone subcutaneously. The efficacy of the additional administration of subcutaneous progesterone as a “rescue” strategy in terms of clinical outcomes remains to be validated. Study design, size, duration We included 356 FET performed at Instituto Bernabeu between January 2019 - August 2020 in a retrospective case-control study. Groups were established according to PG levels on the day of the embryo transfer. The Control Group included: patients with optimal progesterone levels (≥8.8 ng ml); while the Rescue Group included those with suboptimal progesterone levels (&amp;lt;8.8 ng ml). Participants/materials, setting, methods All patients performed frozen embryo transfer after artificial endometrial preparation. All embryo transfers were performed at blastocyst stage after 5 days of progesterone administration. Progesterone levels were assessed the day of the embryo transfer by an electrochemiluminescence immunoassay. Samples were obtained 2–5 hours after the last vaginal progesterone administration. Primary outcome was Ongoing Pregnancy Rates (OPR). Secondary outcomes were pregnancy rates (PR), miscarriage rates (MR) and biochemical miscarriage (BM). Main results and the role of chance 301 patients were included in the Control Group and 55 in the Rescue Group. No significant differences were found between both groups. OPR rate was 34.7% for patients in the control group versus 26.4% in the rescue group (p = 0.240) PR was 52.5% for patients with optimal PG levels vs 54.5% when PG levels were below 8.8 ng/mL. Both BM and MR tend to be higher in women who had low serum PG: BM (21.4% vs 15.5%) and MR (28.6% vs 18.1%), without reaching significant statistical difference. In addition, we analyzed data from a sub-group of patients who received extra subcutaneous progesterone (based on cliniciańs decision), despite having normal serum PG levels. No differences in clinical outcomes between these groups were observed either. OPR was 29%, vs 35.4% (p = 0.241), PR was 51.8% vs 53.7%; BM was 16.7% vs 16.3% and MR was 26.9% vs 17.1% between women who received an extra subcutaneous PG dose versus women who did not, respectively. Weight and BMI distribution were homogeneous across groups. A discreet difference was observed in age distribution (control group mean age 41.6 years vs. 39.7 years in the rescue group). Limitations, reasons for caution The retrospective collection of data and a limited sample size constitutes the main limitations of the study. Significant statistical differences were not found between groups but still differences might be clinically relevant. Larger studies are needed to reach robust conclusions on the strategy. Wider implications of the findings: In AC cycles, when supplemented with additional subcutaneous progesterone, women showing low serum progesterone on cryotransfer day may expect similar clinical outcomes as women with normal levels. Pending on confirmatory studies, this strategy could consider as an alternative to cycle cancellation. Trial registration number Not applicable

P–122 Benefit of use of theophilline in ICSI with testicular sperm

Abstract Study question Would the use of theophylline have an effect on ICSI outcomes? Summary answer The cumulative pregnancy rate after the transfer of fresh and frozen embryos (FET) becomes more important justifying the addition of theophylline as an efficacy variable. What is known already Absolute immotile spermatozoa is one of the most important causes of reduced fertilization and pregnancy rates after ICSI, immotility of testicular spermatozoa is a physiological event resulting from metabolic sperm immaturity. Over the years, there have been numerous attempts to resolve this problem by identification of pharmacological agents that might improve sperm motility. In particular, theophylline turned out to be an effective tool in stimulating motility in human semen and identifying viable sperm in testicular sperm extraction sperm (TESE) patients. aim of this study is to evaluate ICSI outcomes after the use of theophylline to select viable spermatozoa Study design, size, duration This prospective, comparative randomised study was conducted in Fertillia ART center in Tunisia, between november 2017 to november 2020. All patients underwent ICSI cycles with testicular sperm were included. The exclusion criteria consist of cycles with female partner age &amp;gt;42 years and/or cycles with no information about pregnancy outcomes. In our study, the cycles were categorized into two groups according to sperm selection method used in ICSI procdure. Participants/materials, setting, methods The present study include 678 cycles. This cohort was randomly divided into two groups according to method of spermatozoa selection. Treatements arms were performed by theophylline to improve sperm motility (Group A) and the Hyposmotic swelling (HOS) test to indicate sperm vitality (Group B). Clinical and biological parameters, the duration of sperm selection and ICSI outcomes were compared between the two groups. A statistical significant difference was accepted when the p value was &amp;lt;0.05. Main results and the role of chance Baseline clinical parameters were found to be comparable in the two groups. No differences regarding number of oocytes retrieved or MII oocytes were reported . he sperm selection was easier in the group A (time interval : 12±7,2 minutes) than group B (time interval : 22±10 minutes) (p &amp;lt; 0,05). No significative difference was observed between goups in the Fertilization rate (group A : 66% vs group B : 68%) ; Cleavage rate (group A : 76.20% vs. Group B : 75.56%) and Blasulation rate (group A : 63.60% vs. Group B 60.61%) p &amp;gt; 0 ,05. The Cumulative Pregnancy rate for group A (31. 5%) was higher than group B (30%, p &amp;gt; 0 ,05). Indeed, The rate of frozen cycles is significantly higher for group A compared to group B (30% vs. 4.5% p &amp;lt; 0,05). Limitations, reasons for caution Need large sample size. Wider implications of the findings: Theophylline reduces significantly the time needed for sperm selection, Which positively affects the ICSI result. Trial registration number Not applicable

Does the time interval from the end of sperm processing to intrauterine insemination (lab-to-uterus time) affect treatment outcome?

Intra-uterine insemination is an essential component in the treatment of infertility. Success rates are dependent on clinical factors of the female partner, sperm quality, and preparation technique. The effect of the time interval between the end of sperm preparation in the lab, and its injection into the uterine cavity (lab-to-uterus time) is yet to be determined. To investigate the association between the lab-to-uterus time and the pregnancy rate. Partner and donor spermatozoa intra-uterine insemination cycles were included. Preparation for intra-uterine insemination of partners' fresh ejaculate or donor thawed spermatozoa was identical. The time interval from the completion of this stage to the actual intra-uterine injection was recorded. The lab-to-uterus intervals were divided into groups A (0-29min), B (30-59min), C (60-89min), and D (90-180min). Pregnancy was defined as two adequate consecutive doubling levels of hCG and the pregnancy rates were compared between the groups. A total of 267 female patients (138 partner spermatozoa, 129 donors) who had 470 intra-uterine insemination cycles (218 partner spermatozoa, 252 donors) were included. No significant differences in pregnancy rates per treatment cycle were found between the four lab-to-uterus interval groups: A (n=96 cycles; 16.7%), B (n=217; 19.4%), C (n=121; 16.5%), and D (n=36; 36.1%). No difference was found in the pregnancy rates between partner and donor spermatozoa. In the case of fresh partner spermatozoa, the pregnancy rates for groups were as follows: A (n=40 cycles, 20%); B (n=94; 14.9%), C (n=70; 17.1%), and D (n=14; 35.7%) (NS). In the case of thawed donor spermatozoa, the pregnancy rates (per cycle) for groups were as follows: A (n=56; 14.3%), B (n=123; 22.8%), C (n=51; 15.7%), and D (n=22; 36.4)% (NS). The intra-uterine insemination outcome was not affected by the lab-to-uterus time interval. Extended waiting up to 3h for insemination did not have any detrimental effect on pregnancy rates, regardless if partner or donor spermatozoa was used.

El estudio de receptividad endometrial ER®map mejora los resultados reproductivos tras fallos previos de implantación en ciclos de fecundación in vitro

IntroductionRepeated failures in in vitro fertilization are a challenge in fertility treatments, especially in cycles with good quality embryos, where the endometrium appears to be the cause of reproductive failure. Targeted diagnostic tests for evaluation of the optimal endometrium before a new transfer remains a challenge for assisted reproduction treatments. The Endometrial Receptivity Map (ER®map Pronacera Therapeutics SL, Seville, Spain) test provides new endometrial information to customize the next embryo transfer to improve reproductive outcomes for patients with previous implantation failure. ObjectiveThe main objective is to determine whether there are differences in the ongoing pregnancy rate by embryo transfer (OPR), after previous failed embryo transfers with good quality embryos, between the study group (E) with endometrial biopsy for endometrial receptivity study prior to a new transfer, and the control group (C) with new standard transfer without previous endometrial receptivity study. Material and methodsObservational, analytical, longitudinal, retrospective study of cases and historical controls, conducted in the Assisted Reproduction Unit (ARU) of the Hospital Quirónsalud Barcelona, including 104 patients with one or more previous failed embryo transfers with good quality embryos between the periods 2017-2019. Patients with more than one previous failed transfer underwent a diagnostic hysteroscopy, and an analysis was requested with the determination of: lupus anticoagulant, anti-B2-glycoprotein IgG/IgM antibodies, anti-cardiolipin IgG/IgM antibodies, and hereditary thrombophilia as part of the study of implantation failures in the centre. The study group (E), with 55 patients, underwent an endometrial biopsy for the analysis of endometrial receptivity by means of the ER®map (Pronacera Therapeutics SL, Seville, Spain) test prior to scheduling a new personalized transfer (pTE) based on the test result; the control group (C), with 49 patients (historical controls), did not undergo endometrial biopsy for the study of endometrial receptivity after one or more failed embryo transfers with good quality embryos, and a new embryo transfer was scheduled according to the centre's standard protocol (sTE). ResultsThe results of the endometrial receptivity test in the study group were 63.6% receptive and 36.3% non-receptive. The study group had a higher clinical pregnancy rate (PR) than the control group (PR 70.9 vs. 42.8% p< .05), and there was a higher ongoing pregnancy rate (OPR) in the study group (OPR 60 vs. 38.7% p< .05). If we analyse the data according to the number of previous failed transfers, the PR and OPR in the study group was higher than in the control group (PR 72.2 vs, 33.3% NS) (NS: non significance), (OPR 55.5 vs. 33.3% NS) after a previous failed transfer; we also obtained better results in the study group with respect to the control group (PR 84. 2 vs. 56% p< .05), (OPR 73.6 vs. 48% NS) after two previous failed transfers; the results after three or more previous failed transfers were better in the study group (PR 55.5 vs. 27.7% NS), (OPR 50 vs. 27.7% NS). If we eliminate the embryonic factor by analysing only the results with euploid embryo transfers and/or oocyte donation, the PR and OPR were higher in the study group vs the control group (PR 71 vs. 47% NS), and (OPR 60.53 vs. 41.17% NS) respectively. ConclusionsThe study of endometrial receptivity prior to a new transfer improves reproductive results in patients with previous implantation failure, with respect to the control group in which we did not carry out an endometrial study.

Predictive value of the number of frozen blastocysts in live birth rates of the transferred fresh embryos

BackgroundBlastocyst development by extended culture in vitro allows the embryos to ‘select’ themselves, thus successful growth to the blastocyst stage is a reflection of the developmental competence of cleavage stage embryos in a cohort. The study aims to determine whether the number of frozen blastocysts is associated with live birth rates of the transferred fresh embryos.MethodThe retrospective study included 8676 cycles of first fresh embryo transfer from January 2016 to June 2019 at a fertility center of a university hospital. The patients with ≥ 10 oocytes retrieved were divided into three groups according to the number of frozen blastocysts: 0 (group 1), 1–2 (group 2), and ≥ 3 (group 3). The primary outcome measure was the live birth. The secondary outcome measures included clinical pregnancy rates and implantation rates. Logistic regression analysis was also performed.ResultsLive birth rates in patients with ≥ 3 and 1–2 frozen blastocysts were 47.6% and 46.1%, respectively, which were significantly higher than that in patients without blastocyst (36.0%). The clinical pregnancy rate in group 3 was 65.1%, which was also significantly higher than the other two groups (47.0% and 59.2%). The implantation rates were 35.5%, 47.6%, and 56.0% in the three groups, respectively (P < 0.001). Compared with groups of frozen blastocysts, 0 frozen blastocyst yielded a lower rate of live birth (the adjusted odds ratio: 0.526, 95% CI: 0.469, 0.612).ConclusionIn patients with optimal ovarian response that retrieved ≥ 10 oocytes, fresh embryos transfer followed by having blastocysts frozen is a strong indicator of pregnancy achievement, but the number of frozen blastocysts (if not = 0) has limited value in predicting live birth rates.

COMPARATIVE STUDY BETWEEN DIFFERENT TYPES OF VAGINAL PROGESTERONE IN LUTEAL PHASE SUPPORT IN ICSI CYCLES

Background: Assisted reproductive techniques (ART) include all fertility treatments in which the gametes (egg and sperm) are handled outside the human body with the aim of achieving a healthy conception. Common ART procedures include in vitro fertilization (IVF) with or without intracytoplasmic sperm injection (ICSI), fresh or frozen embryo transfer, and IVF with donor oocytes. Luteal phase support through pharmaceutical drugs has been universally agreed. Objective: To compare the effectiveness of different types of vaginal progesterone preparations for luteal support in patients undergoing Intracytoplasmic Sperm Injection. Patients and Methods: The current randomized controlled clinical trial study was conducted on 300 patients who were following at the Assisted Reproductive Technology (ART) unit of the International Islamic Center for Population Studies and Research (IICPSR) of Al-Azhar University over the period from May 2016 to January 2018 after being approved by the ethical committee. The patients were divided into 3 equal groups received Prontogest vaginal suppositories 400 mg once per day, Group B received Crinone 8% (90 mg) vaginal gel once per day and Group C received Endometrin vaginal suppositories once per day. Results: Comparison between studied group A (Prontogest), group B (Crinone) and group C (Endometrin) as regards demographic characteristics revealed no statistically significant differences. As regards the cause of infertility, a statistically significant increase in the number of patients with male and tubal factors in group B (Crinone) than group A (Prontogest). Concerning the laboratory hormonal profile of the studied groups before ICSI, there was a statistically significant increase in FSH and LH levels in group A (Prontogest) than group B (Crinone) and group C (Endometrin). On the other hand, there was a difference between the studied groups as regards prolactin and estrogen levels, but did not reach statistical significance. Comparison between studied groups, as regards Endometrial thickness, number of retrieved oocytes and number of transferred embryos revealed no statistically significant difference. Comparison between the studied groups, as regards pregnancy rates, revealed a statistically significant increase in pregnancy rates in group C than group A. Conclusion: The use of Endometrin vaginal suppositories in patients undergoing ICSI had a statistically significant higher clinical pregnancy rates in comparison to Prontogest vaginal suppositories. On the other hand, Crinone vaginal gel had a higher clinical pregnancy rate than Prontogest.

Impact of previous cesarean delivery on pregnancy outcomes of in vitro fertilization and frozen-thawed embryo transfer

Objective: To investigate the impact of a previous cesarean delivery on pregnancy outcomes of in vitro fertilization and frozen-thawed embryo transfer (FET). Methods: The clinical data of 1 179 patients who received in vitro fertilization and FET in Tianjin Central Hospital of Gynecology Obstetrics from January 2014 to May 2019 and had a history of the previous delivery were retrospectively analyzed. The patients were divided into four groups according to different previous delivery history and the number of embryo transferred: group A (single embryo transfer group with cesarean delivery history, n=338), group B (single embryo transfer group with vaginal delivery history, n=78), group C (double embryo transfer group with cesarean delivery history, n=444), and group D (double embryo transfer group with vaginal delivery history, n=319). The 1∶1 propensity score based on age, body mass index (BMI), infertility duration, basal FSH, basal LH, number of oocytes retrieved and high-quality embryo rate was used to match group A and B (caliper value=0.15), group C and D (caliper value=0.05), and group A and C (caliper value=0.01) respectively to reduce the influence of selection bias. The clinical pregnancy outcomes of patients were compared. Results: (1) Group A and group B were single embryo transfer groups with a total of 77 pairs of matched patients. There were no statistically significant differences in clinical pregnancy rate [42.9% (33/77) vs 45.5% (35/77)], miscarriage rate, preterm birth rate, and neonatal birth weight (all P>0.05). (2) Group C and group D were double embryo transfer groups with a total of 304 pairs of matched patients. The clinical pregnancy rate [42.4% (129/304)] and twin pregnancy rate [9.5% (29/304)] of Group C were significantly lower than those of Group D [53.0% (161/304), 15.5% (47/304) respectively; both P<0.05). There were no statistically significant in miscarriage rate, preterm birth rate and neonatal birth weight between the two groups (all P>0.05). (3) Groups A and C matched 318 pairs of patients. The two groups had no statistical significances in clinical pregnancy rate [38.4% (122/318) vs 45.6% (145/318)], miscarriage rate and preterm birth rate (all P>0.05), but the twin pregnancy rate in group C was significantly higher than that of group A [11.3% (36/318) vs 0.3% (1/318), P<0.01). (4) The occurrence of the low-birth-weight infant were related to gestational age (OR=0.41, 95%CI: 0.32-0.54) and twin pregnancy (OR=4.44, 95%CI: 1.93-10.21), and the occurrence of macrosomia was related to BMI (OR=1.18, 95%CI: 1.06-1.32). Moreover, the previous delivery method was not related to the neonatal birth weight (P>0.05). Conclusions: Patients with different delivery histories receive FET therapy, the pregnancy outcomes of single embryo transfer are not significantly different, and the success rate of double embryo transfer in patients with a cesarean delivery history is low. The neonatal birth weight is not related to the history of the cesarean section. It is recommended that patients with a cesarean delivery history choose elective single embryo transfer to ensure the success rate and to reduce the risk.

Short Ejaculatory Abstinence in Normozoospermic Men is Associated with Higher Clinical Pregnancy Rates in Sub-fertile Couples Undergoing Intra-Cytoplasmic Sperm Injection in Assisted Reproductive Technology: A Retrospective Analysis of 1691 Cycles.

Background:The current WHO abstinence recommendations are ideal only for clinical diagnosis, as in recent years a negative correlation of abstinence duration with good embryo development and clinical pregnancy rate has been seen.Aim:The aim of the study was to evaluate the impact of variation in abstinence period on fertilization, embryo development potential, pregnancy, and miscarriage rate in sub-fertile couples undergoing assisted reproductive technology (ART) treatment.Setting and Design:A prospective analysis was conducted at a tertiary (level 3) infertility care clinic.Materials and Methods:The study included analysis of 1691 cycles for the patient undergoing ART procedures between September 2017 and August 2019. The influence of ejaculatory abstinence (EA) was investigated based on variation in abstinence length with four groups: Group I – 1 day; Group II – 2–5 days; Group III – 6–7 days; and Group IV – EA length of ≥8 days.Statistical Analysis:Analysis of variance and Chi-square test were used to calculate P value.Results:In our primary outcome, we have seen a strong positive correlation of abstinence duration with semen volume, total sperm count, total motile count, and difference between each group was significant. Secondary outcomes showed a significantly higher implantation rate, biochemical pregnancy rate was observed in Group I (1 day) per embryo transfer as compared to longer abstinence groups. This resulted in significantly higher clinical pregnancy rates in Group I 30.0% vs. 25.4% in comparison to longer abstinence groups.Conclusions:Our study has shown duration of abstinence is negatively correlated with positive β-human chorionic gonadotropin rate, clinical pregnancy rate, and implantation rate. Lower miscarriage rate was also observed with shorter abstinence duration.

Impact of Laparoscopic Ovarian Endometriosis Cystectomy on Ovarian Reserve Function

This study was to investigate and analyze the impact of laparoscopic ovarian endometriosis cystectomy on ovarian reserve function. A total of 20 patients undergone with laparoscopic unilateral ovarian teratoma (mature cystic teratoma) cystectomy and 80 cases with ovarian endometriosis cyst given laparoscopic ovarian cystectomy were regarded as the control group and the research group, respectively. Patients in the research group were divided into four group, group A (n=20, unilateral ovarian endometriosis cyst, cyst diameter 0.05. No statistical significance was indicated on hormone levels among groups when ages and types of bilateral ovarian endometriosis cyst were observed in layering, showing p>0.05. Comparing the control group, infertile patients before operation in group A, group B and group presented a higher postoperative pregnancy rate, showing p<0.05; but postoperative pregnancy rate in group D was lower than that in the control group, showing p<0.05. Laparoscopic ovarian endometriosis cystectomy suggested certain influences on ovarian reserve function. Most patients could recover at 1 y postoperatively and the postoperative pregnancy rate for fertile patients could be significantly enhanced by adding gonadotropin releasing hormone agonist, a medicine after the operation.

COMPARISON BETWEEN LETROZOLE ALONE VERSUS LETROZOLE-GONADOTROPHINS COMBINATION IN VERSUS CLOMIPHENE CITRATE – GONADOTROPHINS COMBINATION IN OVARIAN INDUCTION FOR PCOS PATIENT UNDERGOING INTRAUTERINE INSEMINATION

Background: Ovulatory dysfunction is a common cause of infertility and polycystic ovary syndrome (PCOS) is the main reason of this dysfunction. PCOS is the most common endocrinopathy in women of childbearing age. A combination of ovarian stimulation or superovulation with intrauterine insemination (IUI) remains an important option available to an infertility specialist and is a widely used treatment modality for a broad range of indications. Objective: To compare between Letrozole-Gonadotrophins combination in and Clomiphene Citrate – Gonadotrophins combination in ovarian induction for PCOS Patient undergoing Intrauterine Insemination. Patients and methods: prospective chohort study was conducted in International Islamic Center for Population Study and Research, Al-Azhar University including 300 infertile women who already diagnosed as PCOS by Rotterdam 2003 Criteria. Women had been divided randomly into three equal groups: Group (A) were given clomiphene citrate 100 mg daily starting on day 3 till 7 day of cycle plus gonadotrophins (75 IU) once daily starting from 6th day of the cycle till growing follicle reach 18 mm, Group (B) were given letrozole (5mg/ day) starting on day 3 till 7 day of cycle plus gonadotrophins 75 IU once daily starting from 6th day of the cycle till growing follicle reach 18 mm and Group (C) were given letrozole (5mg/ day) starting on day 3 till 7 day of cycle. Results: Women’s ovulation rate in Group (A) was 78% had ovulation while in Group (B) 80% had ovulation and 68% in group (C). There were statistically significant differences between groups. Women’s pregnancy rate in Group (A) was 8% in Group (B) was 7% in group (C) was 4%. There were no statistically significant differences between groups. Group A showed more multiple follicles, more OHSS and then group B and C. more cancellation rate than group B. Group B showed less in multiple follicles and less OHSS than group A and less in cancellation rate than group A and C better in endometrial thickness. Group C Letrozole alone more monofollicular growth, less multiple follicles, less multiple pregnancy, less OHSS and less coast. Than group A and B but had less ovulation rate and more in cancellation rate than group A and B. Conclusion: We can offer ovulation induction and intrauterine insemination (IUI) for PCOS if first lines (lifestyle changes, pharmacotherapy (metformin, clomiphene citrate, letrozole, gonadotrophins) failed.