Clinical Benefits and Safety Profile of Laser-Assisted Zona Thinning in Frozen Cleavage-Stage Embryo Transfers: Evidence from 940 ICSI/FET Cycles

Clinical Benefits and Safety Profile of Laser-Assisted Zona Thinning in Frozen Cleavage-Stage Embryo Transfers: Evidence from 940 ICSI/FET Cycles | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical Benefits and Safety Profile of Laser-Assisted Zona Thinning in Frozen Cleavage-Stage Embryo Transfers: Evidence from 940 ICSI/FET Cycles Maryam Azizi Kutenaei, Sara Hafezpour, Farzaneh Fasahat, Zahra Mamashli, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8877703/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Laser-assisted zona thinning (LAZT) has been proposed to enhance embryo implantation by facilitating zona pellucida (ZP) hatching. This retrospective study evaluates the impact of LAZT on clinical and neonatal outcomes in vitrified-warmed cleavage-stage embryo transfers. A total of 940 patients undergoing ICSI/FET between September 2021 and February 2025 were analyzed. Patients were divided into two groups: 574 underwent LAZT, and 366 served as controls. Subgroup analyses were performed based on age (< 35 and ≥ 35 years) and infertility etiology. The LAZT group exhibited significantly higher biochemical pregnancy (40.1% vs. 29.5%), clinical pregnancy (24% vs. 14.75%), implantation (10.4% vs. 5.75%), and live birth rates (23.3% vs. 14%) compared to controls (P < 0.05). No significant differences were observed in neonatal outcomes such as preterm birth, infant sex, or the presence of congenital malformations. Notably, women aged ≥ 35 years showed more pronounced benefits in biochemical and live birth rates. Patients with polycystic ovary syndrome and multiple infertility factors also demonstrated improved outcomes. However, increased pregnancy complications (11.19% vs 3.92%, P < 0.01) were observed in the LAZT group, necessitating cautious clinical application. Laser-assisted zona thinning pregnancy outcomes assisted reproductive technology (ART) embryo implantation Introduction Treatment with IVF/ICSI stands as the cornerstone of infertility treatment. Annually, approximately three million cycles of IVF/ICSI are carried out worldwide ( 1 ). Despite significant advances in various aspects of IVF/ICSI, the process of embryo implantation still remains a critical factor limiting success rates( 2 ). The chance of conception is approximately 30% per embryo transfer and two-third of unsuccessful pregnancies attributed to challenges in implantation( 3 ). Implantation is a precisely orchestrated biological process that consists of embryo hatching, positioning, attachment, and invasion. Hatching is an essential step in the events leading to successful implantation and failure to hatch is one of the primary reasons for failure to implantation. During hatching, the embryo creates an opening through the zona barrier and exit into the uterine cavity where it implants into the receptive endometrium( 4 ). Prolonged in vitro culture, which can be aggravated by the process of freezing and thawing, has been demonstrated to have the potential to harden or thicken the ZP, affecting implantation ( 5 , 6 ). Already late in the 20th century, it was shown that assisted hatching (AH), which involves artificial disruption of the ZP, could improve embryo implantation( 7 ). Mechanical partial zona dissection (PZD), use of acidic Tyrode’s solution, and laser are often used to achieve ZP destruction( 8 ). However, the success rates following AH have considerably varied according to the patient population and the AH methods( 9 ). Recently, the majority of reproductive centers have opted for laser-assisted hatching (LAH) due to its speed, safety, and precision( 8 , 10 ). An updated Cochrane review indicated that LAH likely contributes to an increase in the clinical pregnancy rate (CPR), but its impact on miscarriage rate and live birth rate (LBR) remained inconclusive( 11 ). Another comprehensive analysis conducted across multiple centers in the US, using data from the National ART Surveillance System involving 35,518 cycles, revealed that LAH procedures were not linked to enhanced pregnancy outcomes( 12 ). Despite numerous randomized controlled trials (RCTs) on this topic, it is still unclear if LAH affects live birth rates (LBR) and neonatal outcomes, and, if so, for which age group it could work better. Therefore, this study aimed to determine the effect of laser assisted zona thinning on the clinical and neonatal outcomes of vitrified-thawed cleavage embryo transfers among patients of varying ages and diverse infertility etiologies. Material and methods Study populations This retrospective, observational study was conducted at the infertility center of Hormozgan University of Medical Sciences in Bandar Abbas, Iran affiliated with Hormozgan University of Medical Sciences, bearing the ethical code IR.HUMS.REC.1402.319. Patients who underwent ICSI/ FET constituted the target population of this study. In total 940 eligible patients were divided into two groups, categorized by whether or not they received laser-assisted zona thinning. Within each group, patients were further divided into two subgroups based on age: <35 and ≥ 35 years and by the specific causes of infertility. The exclusion criteria were as follows: (a) patients with severe uterine factors or chromosomal abnormalities (b) Fresh embryo transfer (c) day 5 embryo transfer, and (d) missing follow-up data. Ovarian stimulation, oocyte retrieval, fertilization and culture conditions were similar between groups. Endometrial preparation regimen Vitrified-warmed cleavage embryo transfer was performed following the artificial preparation of the endometrium with exogenous steroids. Briefly, patients were administered oral estradiol (E2) valerate at a dosage of 2mg/8h for 10–12 days from the onset of menstruation. Upon ultrasound confirmation of an optimal endometrial thickness (≥ 7 mm with a triple-line pattern), estradiol valerate at the same dosage was sustained, and intramuscular administration of 50mg of progesterone commenced. Embryo transfer was scheduled on Day 4 following the start of progesterone treatment. Luteal phase support was maintained until 12th week of pregnancy or until the day of pregnancy test if negative. Freezing and thawing Vitrification was performed using a Cryotop device and vitrification kit (KITAZATO BioPharma Co., Japan) following the manufacturer's instructions. Briefly, the embryos were transferred from the culture media to the equilibration solution (ES) for 7 min to restore their volume. Subsequently, they were transferred to a vitrification solution (VS) for 45–60 s, ensuring complete replacement of the embryo's extracellular fluid with VS. Finally, embryos were loaded at the anterior end of Cryotop with extremely small amounts of VS and immediately immersed into liquid nitrogen. Thawing of vitrified embryos was conducted using a thaw kit (VT102, Kitazato Corporation). In short, the anterior end of the Cryotop containing embryos was immersed into the thawing solution (TS) for 1 minute. Then, the embryos were transferred to the base of the diluent solution (DS) for 3 minutes, underwent a 5-minute wash with washing solution (WS) for 5 minutes. Finally, they were transferred to the culture medium (Sage 1step, CooperSurgical, Denmark) and incubated for 3 hours at 37°C and 6% CO 2 . Embryo selection and transfer The post-thaw embryos were transferred at cleavage stage by the guidance of abdominal ultrasound. Two to four embryos were transferred, depending on the patient's age and embryo availability and quality. Embryos were graded as proposed by Depa-Martynow et al( 13 ). This evaluation involved considering the number and quality of blastomeres, along with the percentage of fragmentation. The grading criteria were as follows: Grade A represented the highest quality, comprising embryos with a minimum of 7 blastomeres (7–9 blastomeres) and cytoplasmic fragmentation of up to 20%. Grade B included embryos with 7–9 blastomeres and cytoplasmic fragmentation exceeding 20%. Grade C encompassed 4–6 cell embryos exhibiting cytoplasmic fragmentation up to 20%, while Grade D denoted the lowest quality, consisting of 4–6 cell embryos with cytoplasmic fragmentation surpassing 20%( 14 ). Laser-assisted zona thinning procedure The laser-assisted hatching was carried out using the ZILOS tk Zone Infrared Laser Optical System (Hamilton Thorne Instruments Biosciences, Beverly, Massachusetts). Briefly, a 1480 nm invisible, in a computer-controlled non-contact laser diode beam, collimated and aligned with a 1-mW visible 670-nm diode laser aiming beam, entered an inverted microscope (Olympus IX71, Tokyo, Japan). It was guided through various mirrors and then focused by the microscope's ×40 objective lens. The power available at the objective's image plane was 47 milliwatts, yielding a maximum power density of 94 kW/cm 2 . The embryos were handled within their original culture medium in an embryo culture dish, positioned on the displacement stage of the diaphot inverted microscope. Each embryo was precisely situated within a region of the Zona Pellucida (ZP) at the targeted point of focus. Ensuring precision, the aiming spot was accurately positioned between the ZP's middle and outer edge. In order to reduce laser negative impacts, the target was placed at a specific area of the Zona Pellucida (ZP), ensuring a distinct separation between the inner ZP membrane and the blastomeres. The size of the aperture was controlled based on the duration of irradiation. In this study, one ablation lasting 2.8 ms was adequate to generate a defect of 12 µm in diameter. The laser operated at 100% power, three to five ablations of 2.8 ms were applied around a specific point on the Zona Pellucida (ZP) until 50–60% of the total ZP thickness was affected. Importantly, the inner membrane of the ZP remained intact without complete breach. The AH procedure was carried out in approximately 20 s per embryo. Following the LAH procedure, to prevent potential toxicity from byproducts resulting from the laser's interaction with organic components of the Zona Pellucida (ZP), the embryos underwent a rinsing process. They were then transferred to a culture dish with 1ml sage 1 step (Cooper Surgical, Denmark) containing 10% serum protein substitute (SPS; Quinn’s; SAGE, USA) and cultured under of 6% CO2. All zona thinning procedures were conducted on the morning of D4, at least 1 hour before the embryo transfer. Endpoints The main focus centered on the live birth rate (the number of deliveries that resulted in a live born neonate per transfer) as the primary outcome. Secondary outcomes included the biochemical pregnancy rate (defined by a pregnancy diagnosed only by the detection of beta hCG in serum per transfer), clinical pregnancy rate (determined by the visualization of at least one gestational sac in ultrasound examination per transfer), implantation rate ( defined as the percentage of gestational sacs of the total number of embryos transferred), miscarriage rate (expressed as the spontaneous loss of an intra-uterine pregnancy before 12 completed weeks of gestation). Additionally, neonatal aspects like preterm birth, malformation rate, and the sex of the baby, were considered. Statistical analysis Data are presented as mean ± standard deviation (SD) for continuous variables, and as frequencies and percentages for categorical variables, where appropriate. Comparisons of numerical variables between study groups were performed using the student’s t-test, while categorical variables were analyzed using the Chi-square (χ²) test. A p-value less than 0.05 was considered statistically significant. All analyses were conducted with the Statistical Package for Social Sciences (SPSS) version 19.0 (SPSS Inc., USA). Results A total of 940 cryopreserved cleavage embryo transfer cycles conducted between September 2021 and February 2025 were included in this study. All patients were divided into two groups: 574 cases underwent laser-assisted zona thinning (LAZT), while 366 cases served as control group without laser-assisted zona thinning (non-LAZT). The mean age of patients was comparable in both groups (32.95 ± 5.44 versus 32.44 ± 5.68). No significant differences were observed in the BMI (26 ± 2.5 versus 26. 2 ± 2.8) survival rate of the vitrified embryos after warming (97.0% versus 97.5%), the mean number of embryos transferred (3.06 ± 0.22 versus 2.91 ± 0.46), and the number of high-quality transferred embryos (2.43 versus 2.42) between the two groups (P > 0.05). In addition, the duration of infertility (5.1 ± 1.29 versus 5.2 ± 1.3) and endometrial thickness (8.22 ± 1.4 versus 8.13 ± 0.98) did not significantly differ between the two groups (P > 0.05) (Table 1 ). Table 1 Comparison of demographic, clinical and neonatal parameters between intervention (LAZT) group and control group Parameters Control Intervention P value No. of cycles 366 574 Female age (year, mean ± SD) 32.44 ± 5.68 32.95 ± 5.44 0.17 Female BMI 26.2 ± 2.8 26 ± 2.5 0.22 Duration of infertility (year, mean ± SD) 4.52 ± 1.29 5.54 ± 1.10 0.38 Endometrial thickness (mm) 8.22 ± 1.31 8.15 ± 1.07 0.31 Embryo survival (%) 97.50% 97% 0.26 Embryos transferred (mean ± SD) 2.91 ± 0.46 3.06 ± 0.22 0.17 High-quality embryo transferred (n, %) 2.42(85.6%) 2.43(84.8%) 0.17 Biochemical pregnancy (%, n) 108/366(29.5%) 230/574(40.1%) 0.001* Clinical pregnancy (%, n) 54/366(14.75%) 138/574(24%) 0.001* Implantation (%, n) 63/1096 (5.75%) 180/1723 (10.4%) < 0.001* Live birth (%, n) 51/366(14%) 134/574(23.3%) < 0.001* Number of live(n) 59 169 0.02* Miscarriage (%, n) 3/54(5.5%) 4/138(2.9%) 0.37 Multiple pregnancy (%, n) 8/54(14.8%) 35/138(25.3%) 0.01* Ectopic pregnancy (%, n) 0/54(0%) 0/138(0%) - Birth defect (%, n) 0/51 0/134 - Preterm birth (%, n) 11/51(21.5%) 43/134(32%) 0.16 Pregnancy complication (%, n) 2/51(3.92%) 12/134(11.19%) < 0.01* Gender (girl) 31/59(52.5%) 86/169(49.7%) 0.7 Gender (boy) 28/59(47.5%) 83/169(48%) 0.94 Continuous variables (e.g., age, BMI, endometrial thickness, number of embryos transferred) were tested for normality using the Shapiro–Wilk test. Normally distributed variables were summarized as mean ± standard deviation (SD) and compared between groups using the independent Student’s t-test. Categorical variables (e.g., biochemical pregnancy, clinical pregnancy, live birth, neonatal sex) were expressed as frequencies and percentages, and comparisons between groups were performed using the chi-square test or Fisher’s exact test when cell counts were < 5. Statistical significance was defined as P < 0.05 \ The biochemical pregnancy (40.1% versus29.5%), clinical pregnancy (24% versus 14.75%) and implantation rates (10.4% versus 5.75%) were significantly higher in the intervention group than in the control group (P < 0.05). The live birth rate (23.3% versus 14%), multiple pregnancy rates (25.3% versus 14.8%), and pregnancy complication (11.19% versus 3.92%) were also higher in the intervention group than the control group. Subgroup analysis comparing the two groups in women aged less than 35 years and in women aged 35 years or more shows the higher biochemical pregnancy, clinical pregnancy, and live birth rate in women aged 35 years or more with laser-assisted hatching (Table 2 ) compared to control group, while in women aged less than 35 years there were significant differences between control and intervention group in regard to multiple pregnancy and pregnancy complications. Moreover, the implantation rate and biochemical pregnancy showed a trend towards an increase in intervention group (11.2% versus 7%, p = 0.08, and 43% versus 35.6%, p = 0.07, respectively) compared to the control group. Table 2 Subgroup Analysis of Clinical and Neonatal Outcomes Based on Maternal Age Parameters Control Group (Age < 35) (n = 213) Intervention Group (Age < 35) (n = 402) P value Control Group (Age ≥ 35) (n = 153) Intervention Group (Age ≥ 35) (n = 172) P value Clinical Outcomes Biochemical Pregnancy, n (%) 76 (35.6) 173 (43.0) 0.07 32 (20.9) 57 (33.1) 0.01* Clinical Pregnancy, n (%) 41 (19.2) 103 (25.6) 0.41 13 (8.5) 35 (20.3) 0.04* Implantation Rate, % (n) 7.4 (47 / 633) 11.2 (135 / 1207) 0.08 3.5 (16 / 463) 8.7 (45 / 516) 0.63 Live Birth, n (%) 38 (17.8) 100 (24.8) 0.35 13 (8.5) 34 (19.7) 0.06 Miscarriage, % (n) 7.3 (3 / 41) 1.0 (1 / 103) 0.10 0 (0) 8.6 (3 / 35) 0.38 Multiple pregnancy, % (n) 14.6 (6 / 41) 26.2 (27 / 103) 0.09 15.4 (2 / 13) 22.8 (8 / 35) 0.77 Neonatal Outcomes Preterm Birth, % (n) 21.1 (8 / 38) 31.0 (31 / 100) 0.17 23.1 (3 / 13) 35.2 (12 / 34) 0.25 Pregnancy Complication, % (n) 2.6 (1 / 38) 27.0 (27 / 100) 0.002* 7.7 (1 / 13) 35.3 (12 / 34) 0.02* Infant Sex (Girl), % (n) 48.8 (21 / 43) 57.1 (72 / 126) 0.22 62.5 (10 / 16) 32.6 (14 / 43) 0.01* Infant Sex (Boy), % (n) 51.2 (22 / 43) 42.9 (54 / 126) 0.63 37.5 (6 / 16) 65.1 (28 / 43) 0.07 Data are presented as n (%) unless otherwise specified. Statistical analysis was performed using the Chi-square test for categorical variables. A P value of < 0.05 was considered statistically significant. The subgroup analysis based on the cause of infertility suggests that laser zona thinning may offer significant benefits in patients with PCOS and multiple factors infertility, particularly improving biochemical and live birth rates. Benefits in patients with poor ovarian reserve were also noted for biochemical pregnancy. However, no significant improvements were found in male factor, tubal factor, or unexplained infertility groups. Notably, pregnancy complications were increased in some intervention groups, warranting careful consideration in clinical practice (Tables 3 & 4 ). Table 3 Subgroup Analysis of Clinical Outcomes Based on Infertility Etiology Parameters Clinical Outcomes Biochemical Pregnancy, n (%) Clinical Pregnancy, n (%) Implantation Rate, n (%) Live Birth, n (%) Miscarriage, n (%) Multiple Pregnancy, n (%) Male Factor (n = 107) Control (n = 59) 16 (27.1) 14 (23.7) 8.5 (15 / 177) 13 (22.0) 7.1 (1 / 14) 7.1 (1 / 14) Interv. (n = 48) 17 (35.4) 12 (25.0) 9.6 (14 / 145) 12 (25.0) 0.0 (0 / 0) 16.7 (2 / 12) P value 0.36 0.24 0.49 0.28 0.75 0.46 Tubal Factor (n = 39) Control (n = 34) 9 (26.5) 6 (17.6) 5.8 (6 / 104) 6 (17.6) 0.0 (0) 0.0 (0) Interv. (n = 5) 1 (20.0) 0.0 (0) 0.0 (0) 0.0 (0.0) 0.0 (0) 0.0 (0) P value 0.76 0.24 0.24 Unexplained (n = 152) Control (n = 84) 36 (42.9) 15 (17.9) 7.8 (20 / 255) 15 (17.9) 0.0 (0) 26.7 (4 / 15) Interv. (n = 68) 21 (30.9) 12 (17.6) 9.3 (19 / 204) 12 (17.6) 0.0 (0 / 0) 41.7 (5 / 12) P value 0.13 0.3 0.32 0.22 0.43 PCOS (n = 359) Control (n = 90) 30 (33.3) 13 (14.4) 5.6 (15 / 268) 11 (12.2) 15.4 (2 / 13) 15.4 (2 / 13) Interv. (n = 269) 125 (46.5) 77 (28.6) 12.0 (97 / 807) 73 (27.1) 5.2 (4 / 77) 23.4 (18 / 77) P value 0.02* 0.06 0.48 0.04* 0.2 0.52 Poor Ovarian Response (n = 245) Control (n = 77) 14 (18.2) 5 (6.5) 2.7 (6 / 226) 5 (6.5) 0.0 (0) 20.0 (1 / 5) Interv. (n = 168) 57 (40.0) 30 (17.9) 7.7 (39 / 504) 30 (17.9) 0.0 (0) 23.3 (7 / 30) P value 0.01* 0.26 0.55 0.23 0.87 Mixed Factors (n = 33) Control (n = 20) 3 (15.0) 1 (5.0) 6.3 (1 / 61) 1 (5.0) 0.0 (0) 0.0 (0) Interv. (n = 13) 7 (53.8) 5 (38.5) 17.9 (7 / 39) 5 (38.5) 0.0 (0) 40.0 (2 / 5) P value 0.01* 0.31 0.54 0.31 0.54 Data are presented as n (%) unless otherwise specified. The denominator for percentage calculations is the number of cycles in the subgroup for primary outcomes (e.g., Live Birth) and the number of pregnancies for pregnancy-based outcomes (e.g., Miscarriage). "—" indicates that a P value or percentage could not be calculated due to a zero value in one of the comparison groups (e.g., no clinical pregnancies). Statistical analysis was performed using the Chi-square test for categorical variables. A P value of < 0.05 was considered statistically significant. Interv., Intervention (LAZT) Group. Table 4 Subgroup Analysis of Neonatal Outcomes Based on Infertility Etiology Parameters Neonatal Outcomes Preterm Birth, n (%) Pregnancy Complication, n (%) Infant Sex (Girl), n (%) Infant Sex (Boy), n (%) Male Factor (n = 107) Control (n = 59) 7.7 (1 / 13) 7.7 (1 / 13) 53.8 (7 / 13) 46.2 (6 / 13) Interv. (n = 48) 16.7 (2 / 12) 25.0 (3 / 12) 42.9 (6 / 14) 57.1 (8 / 14) P value 0.51 0.25 0.77 0.33 Tubal Factor (n = 39) Control (n = 34) 16.7 (1 / 6) 0.0 (0) 66.7 (4 / 6) 33.3 (2 / 6) Interv. (n = 5) 0.0 (0) 0.0 (0) 0.0 (0) 0.0 (0) P value Unexplained (n = 152) Control (n = 84) 33.3 (5 / 15) 6.7 (1 / 15) 55.0 (11 / 20) 45.0 (9 / 20) Interv. (n = 68) 41.7 (5 / 12) 41.7 (5 / 12) 44.4 (8 / 18) 55.6 (10 / 18) P value 0.67 0.02* 0.54 0.12 PCOS (n = 359) Control (n = 90) 36.4 (4 / 11) 0.0 (0) 46.2 (6 / 13) 53.8 (7 / 13) Interv. (n = 269) 35.6 (26 / 73) 31.5 (23 / 73) 52.8 (47 / 89) 47.2 (42 / 89) P value 0.65 0.04* 0.74 0.99 Poor Ovarian Response (n = 245) Control (n = 77) 0.0 (0) 0.0 (0) 50.0 (3 / 6) 50.0 (3 / 6) Interv. (n = 168) 33.3 (10 / 30) 26.7 (8 / 30) 50.0 (19 / 39) 50.0 (19 / 39) P value 0.13 0.19 0.28 0.28 Mixed Factors (n = 33) Control (n = 20) 0.0 (0) 0.0 (0) 0.0 (0) 100 (1 / 1) Interv. (n = 13) 40.0 (2 / 5) 40.0 (2 / 5) 71.4 (5 / 7) 28.6 (2 / 7) P value 0.54 0.54 0.36 0.32 Data are presented as n (%) unless otherwise specified. The denominator for percentage calculations is the number of cycles in the subgroup for primary outcomes (e.g., Live Birth) and the number of pregnancies for pregnancy-based outcomes (e.g., Miscarriage). "—" indicates that a P value or percentage could not be calculated due to a zero value in one of the comparison groups (e.g., no clinical pregnancies). Statistical analysis was performed using the Chi-square test for categorical variables. A P value of < 0.05 was considered statistically significant. Interv., Intervention (LAZT) Group. Male Factor Subgroup In the male factor subgroup, the intervention group (n = 48) had a higher biochemical pregnancy rate (35.4% vs. 27.1%, P = 0.36) and clinical pregnancy rate (25% vs. 23.7%, P = 0.24) compared to the control group (n = 59), though these differences were not statistically significant. The implantation rate was 9.6% in the intervention group versus 8.5% in the control group (P = 0.49), with no significant difference observed. Live birth rates were 25% in the intervention group and 22% in the control group (P = 0.28), showing no significant difference. PCOS Subgroup In patients with PCOS, the LAZT group (n = 269) demonstrated significantly higher biochemical pregnancy (46.5% vs. 33.3%, P = 0.02) and live birth rates (27.1% vs. 12.2%, P = 0.04) compared to the control group (n = 90). The clinical pregnancy rate was also higher in the intervention group (28.6% vs. 14.4%), though this difference approached but did not reach statistical significance (P = 0.06). Poor Ovarian Response Subgroup For patients with poor ovarian response, the intervention group (n = 168) showed a significantly higher biochemical pregnancy rate compared to controls (40.0% vs. 18.2%, P = 0.01). While live birth rates were numerically higher in the LAZT group (17.9% vs. 6.5%), this difference was not statistically significant (P = 0.23). Unexplained Infertility Subgroup In cases of unexplained infertility, no significant differences were observed between the intervention (n = 68) and control (n = 84) groups for biochemical pregnancy (30.9% vs. 42.9%, P = 0.13), clinical pregnancy (17.6% vs. 17.9%, P = 0.3), or live birth rates (17.6% vs. 17.9%, P = 0.22). However, pregnancy complications were significantly higher in the intervention group (41.7% vs. 6.7%, P = 0.02). Mixed Factors Infertility Subgroup Among patients with mixed infertility factors, the LAZT group (n = 13) had a significantly higher biochemical pregnancy rate than the control group (53.8% vs. 15.0%, P = 0.01). Live birth rates were also higher (38.5% vs. 5.0%), though this difference was not statistically significant (P = 0.31), likely due to the small sample size. The subgroup analysis based on the cause of infertility suggests that laser zona thinning may offer significant benefits in patients with PCOS and multiple factors infertility, particularly improving biochemical and live birth rates. Benefits in patients with poor ovarian reserve were also noted for biochemical pregnancy. However, no significant improvements were found in male factor, tubal factor, or unexplained infertility groups. Notably, pregnancy complications were increased in some intervention groups, warranting careful consideration in clinical practice (Tables 3 & 4 ). Discussion The role of assisted hatching (AH) in ART remains a controversial issue in clinical practice. While some studies suggest potential benefits, others report no significant improvements in pregnancy outcomes particularly when it is applied universally in women who already have a good prognosis. To address this uncertainty, our study analyzed 940 ICSI/ FET cycles, comprising 574 with laser-assisted zona thinning (LAZT) and 366 controls. The results reveal that LAZT is associated with significantly improved biochemical, clinical pregnancy, implantation, live birth, and multiple pregnancy rates compared to non-LAZT in this population. However, LAZT is also associated with higher rate of pregnancy complications. Despite this, our findings suggest that LAZT treatment does not adversely affect neonatal outcomes. The zona pellucida (ZP) is a transparent, non-cellular glycoprotein layer that surrounds the plasma membrane of oocytes and early embryos. This specialized layer is essential for successful fertilization and early embryonic development. In a mature human oocyte, the ZP typically measures approximately 15–18 µm in thickness. During natural embryo development, the ZP thins and eventually breaks down, allowing the blastocyst to hatch and implant into the uterine lining. This hatching process is essential for successful implantation and is typically completed by days 4 to 5 post-fertilization. However, in assisted reproductive technologies (ART), in vitro culture for extended periods and cryopreservation, can lead to ZP hardening. This hardening reduces the ZP's susceptibility to enzymatic degradation, making it more challenging for the embryo to hatch( 15 ). Consequently, embryos may face difficulties in escaping the ZP, potentially leading to implantation failure. To address this issue, techniques like AH are employed. In the late 1980s to early 2000s, various chemical and mechanical methods were explored for assisted hatching to address challenges in embryo implantation. But nowadays, the 1.48 µm infrared diode laser system has become the most widely utilized technique for AH in ART. Recent evidence suggests that LAH is related to a higher clinical pregnancy rate, embryo implantation rate, and multiple pregnancy rate( 16 ). However, LAH is unlikely to increase live birth rates( 16 ). In a large retrospective study, McLaughlin et al. found that LAH significantly reduced live birth rates in both good and poor prognosis patients undergoing fresh embryo transfer. The study reported a 4.7% lower live birth rate in the AH group compared to the control group( 17 ). In our study, obvious benefit on live birth rate was found when LAZT was used along with a vitrified cleavage embryo. Consistent with our findings, Endo et al. also reported that LAH substantially increased live birth rates in patients undergoing single vitrified blastocyst transfer( 18 ). The discrepancy in outcomes may be attributed to differences in AH methodology used, extent of LAH, patient selection criteria, embryo quality assessment, the method of cryopreservation, ET type, the conception mode, the sample size, and study design. LAH is considered a safe method in ART, as it does not adversely affect neonatal outcomes, including congenital malformations. In our study, we evaluated neonatal outcomes in all infants born following vitrified cleavage transfer with LAZT and compared them to all infants from a control group. Our findings revealed no significant differences between the two groups in terms of preterm birth, infant sex, or the incidence of congenital malformations in general population. These results suggest that LAH does not compromise neonatal health. However, our study identified an increased rate of pregnancy complications in the LAZT group. We hypothesized this may be related to the higher multiple pregnancy rate in the AH group underscoring the importance of careful patient selection and embryo transfer protocols to balance the benefits of LAH with the potential risks associated with multiple gestations. While some studies have reported no significant differences in obstetric and neonatal outcomes following AH( 18 ), others have observed higher rates of multiple pregnancies( 16 , 19 ), which are associated with increased maternal and fetal risks. Our sub-analyses suggest that LAH benefits are particularly evident in older women (≥ 35 years), in patients with PCOS or multifactorial infertility, and to some extent among those with poor ovarian reserve. One may have a concern about embryo quality between the LAH and control subgroups. To mitigate this potential bias, a rigorous grading and selection process was applied. An experienced embryologist assessed and selected embryos for transfer, ensuring that both comparable subgroups received embryos of similar quality. Moreover, it should be emphasized that all patients received the same freezing, thawing, and endometrial preparation protocols. Previous studies indicate that LAH can enhance embryo implantation by facilitating hatching, particularly in challenging cases such as advanced maternal age or patients with repeated implantation failure( 20 ). For instance, Ghannadi et al. found that in women ≥ 35 years, LAH significantly increased both chemical pregnancy (30.12% vs 18.96%) and clinical pregnancy rates (27.71% vs 16.37%) compared to no LAH( 21 ). A recent retrospective analysis for vitrified-warmed embryo transfers also suggests that in women > 40, LAH may improve pregnancy outcomes( 22 ). With increasing age, the zona pellucida is thought to become harder or less penetrable, possibly due to increased cross-linking or changes in zona glycoproteins. In parallel, embryo competence tends to decline with age, which can impede natural hatching. Thus, when fewer high-quality embryos are available, interventions like LAH may increase the likelihood that the embryos present will successfully implant. Regarding the etiology of infertility, the majority of patients appear to benefit from AH, with the effect being more pronounced in individuals with PCOS or multifactorial infertility. While the precise mechanisms remain to be fully elucidated, several factors may explain its efficacy in these populations. In PCOS, hormonal imbalances can lead to reduced endometrial receptivity, hindering embryo implantation. Additionally, despite a higher number of oocytes retrieved, their quality may be compromised, resulting in embryos less capable of successful implantation. In contrast, patients with multifactorial infertility often experience combined factors affecting implantation, and AH may help overcome one of the potential barriers to successful implantation. This study has several limitations. As a retrospective, single-center observational analysis without randomization, it is subject to potential selection bias and unmeasured confounding. The transfer of multiple embryos increases the likelihood of multiple gestations, which may independently influence pregnancy complications and makes it difficult to fully isolate the effect of LAZT. Some subgroup analyses, particularly those involving rare outcomes such as congenital anomalies, were limited by small sample sizes and may be underpowered. Additionally, the study lacked information on embryo chromosomal status, including aneuploidy, which is an important determinant of implantation and pregnancy outcomes. Without genetic data, it remains unclear whether the observed differences reflect the effect of LAZT itself or variations in underlying embryo viability. Conclusion Our findings suggest that LAZT may improve clinical outcomes across the general population, with more pronounced benefits observed in patients aged ≥35 years and those with PCOS or multiple infertility factors. While LAZT does not appear to adversely affect neonatal health, the increased multiple pregnancy rate and associated complications necessitate careful patient selection and counseling. Further research is warranted to confirm these findings and optimize assisted hatching protocols to minimize associated risks. Declarations Author Contribution MAK: Data collection, embryology procedures, data analysis, writing – original draft.SH: Clinical data collection, patient management, literature review, manuscript editing.FF: Statistical analysis, data interpretation, manuscript revision.ZM: Data coordination, patient follow-up, preparation of tables and figures.EN: Laboratory procedures, embryo handling, data quality control.FM: Clinical data verification, contribution to discussion, and interpretation.ES: Study conception and design, supervision, data interpretation, and final approval of the manuscript.All authors have reviewed and approved the final manuscript and agree to be accountable for its content. Acknowledgement The authors would like to express their sincere gratitude to the staff of the Fertility and Infertility Research Center at Hormozgan University of Medical Sciences for their invaluable technical and clinical support throughout this study. We also extend our appreciation to the embryology and nursing teams for their dedication in patient care and laboratory procedures. We thank all patients who generously agreed to participate in this research. Their cooperation made this study possible. Finally, we acknowledge the Hormozgan University of Medical Sciences for providing institutional support for this project. Ethics approval The study protocol received approval from the Institutional Review Board of Hormozgan University of Medical Sciences (approval ID: IR.HUMS.REC.1402.319). Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Conflict of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Consent to participate Written informed consent was obtained from all individual participants included in the study. Clinical trial number Not applicable. References Chambers GM, Dyer S, Zegers-Hochschild F, de Mouzon J, Ishihara O, Banker M et al (2021) International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2014. Hum Reprod 36(11):2921–2934 De Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T et al (2020) ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod open 2020(1):hoz038 Kim S-M, Kim J-S (2017) A review of mechanisms of implantation. Dev Reprod 21(4):351 Kutlu P, Atvar O, Vanlioglu OF (2010) Laser assisted zona thinning technique has no beneficial effect on the ART outcomes of two different maternal age groups. J Assist Reprod Genet 27:457–461 Ricardo Loret de Mola J, Garside WT, Bucci J, Tureck RW, Heyner S (1997) Analysis of the human zona pellucida during culture: correlation with diagnosis and the preovulatory hormonal environment. J Assist Reprod Genet 14:332–336 Elnahas T, Tawab N, Azmy O, Elnoury A, El-Faissal Y, Fouad T et al (2017) Prospective randomized trial on the use of laser assisted hatching for transfer of frozen/thawed embryos in human Intracytoplasmic Sperm injection. Middle East Fertility Soc J 22(4):309–312 Cohen J, Elsner C, Kort H, Malter H, Massey J, Mayer MP et al (1990) Impairment of the hatching process following IVF in the human and improvement of implantation by assisting hatching using micromanipulation. Hum Reprod 5(1):7–13 Balaban B, Urman B, Alatas C, Mercan R, Mumcu A, Isiklar A (2002) A comparison of four different techniques of assisted hatching. Hum Reprod 17(5):1239–1243 Magli M, Gianaroli L, Ferraretti A, Fortini D, Aicardi G, Montanaro N (1998) Rescue of implantation potential in embryos with poor prognosis by assisted zona hatching. Hum Reprod (Oxford England) 13(5):1331–1335 Wei C, Xiang S, Liu D, Wang C, Liang X, Wu H et al (2023) Laser-assisted hatching improves pregnancy outcomes in frozen-thawed embryo transfer cycles of cleavage-stage embryos: a large retrospective cohort study with propensity score matching. J Assist Reprod Genet 40(2):417–427 Lacey L, Hassan S, Franik S, Seif MW, Akhtar MA Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI)). Cochrane Database Syst Reviews. 2021(3). Kissin DM, Kawwass JF, Monsour M, Boulet SL, Session DR, Jamieson DJ et al (2014) Assisted hatching: trends and pregnancy outcomes, United States, 2000–2010. Fertil Steril 102(3):795–801 Depa-Martynow M, Jedrzejczak P, Pawelczyk L (2007) Pronuclear scoring as a predictor of embryo quality in in vitro fertilization program. Folia Histochem Cytobiol 45(I):85–89 Masoudi M, Yamini N, Salehi F, Aflatoonian R, Kutenaee MA, Esfandiyari S et al (2021) Notch signaling pathway in cumulus cells reflecting zygote and embryo quality in polycystic ovary syndrome. Arch Gynecol Obstet 304:1097–1105 Carroll J, Depypere H, Matthews C (1990) Freeze–thaw-induced changes of the zona pellucida explains decreased rates of fertilization in frozen–thawed mouse oocytes. Reproduction 90(2):547–553 Zeng M, Su S, Li L (2018) The effect of laser-assisted hatching on pregnancy outcomes of cryopreserved-thawed embryo transfer: a meta-analysis of randomized controlled trials. Lasers Med Sci 33(3):655–666 McLaughlin JE, Choi BY, Liu Q, Gelfond JA, Robinson RD, Chang TA et al (2019) Does assisted hatching affect live birth in fresh, first cycle in vitro fertilization in good and poor prognosis patients? J Assist Reprod Genet 36(12):2425–2433 Endo Y, Mitsuhata S, Hayashi M, Fujii Y, Motoyama H (2021) Laser-assisted hatching on clinical and neonatal outcomes in patients undergoing single vitrified Blastocyst transfer: A propensity score–matched study. Reproductive Med Biology 20(2):182–189 Li D, Yang D-L, An J, Jiao J, Zhou Y-M, Wu Q-J et al (2016) Effect of assisted hatching on pregnancy outcomes: a systematic review and meta-analysis of randomized controlled trials. Sci Rep 6(1):31228 Lu X, Liu Y, Cao X, Liu S-Y, Dong X (2019) Laser-assisted hatching and clinical outcomes in frozen-thawed cleavage-embryo transfers of patients with previous repeated failure. Lasers Med Sci 34(6):1137–1145 Ghannadi A, Kazerooni M, Jamalzadeh F, Amiri S, Rostami P, Absalan F (2011) The effects of laser assisted hatching on pregnancy rates. Iran J reproductive Med 9(2):95 Kanoi R, Ramakrishnan S, Mondal S, Gutgutia R (2023) P-230 Does laser-assisted hatching improve pregnancy rates: a retrospective analysis. Hum Reprod 38(Supplement1):dead093 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8877703","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":609906308,"identity":"ff871b3a-be11-4eb3-8992-5fda8da94e2f","order_by":0,"name":"Maryam Azizi Kutenaei","email":"","orcid":"","institution":"Hormozgan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Maryam","middleName":"Azizi","lastName":"Kutenaei","suffix":""},{"id":609906310,"identity":"87b091c4-0c9b-4d6b-a639-8dc1860e2f4b","order_by":1,"name":"Sara Hafezpour","email":"","orcid":"","institution":"Hormozgan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Hafezpour","suffix":""},{"id":609906317,"identity":"0bfdeff0-cdc9-4641-a349-aa3276f1fc50","order_by":2,"name":"Farzaneh Fasahat","email":"","orcid":"","institution":"Shahid Sadoughi University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Farzaneh","middleName":"","lastName":"Fasahat","suffix":""},{"id":609906323,"identity":"3829299c-69ea-432f-9f87-f98e0159d1cd","order_by":3,"name":"Zahra Mamashli","email":"","orcid":"","institution":"Hormozgan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Zahra","middleName":"","lastName":"Mamashli","suffix":""},{"id":609906324,"identity":"1564c7a6-543a-47c9-84e6-ccad301f07a6","order_by":4,"name":"Elham Namjoo","email":"","orcid":"","institution":"Hormozgan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Elham","middleName":"","lastName":"Namjoo","suffix":""},{"id":609906325,"identity":"1b3a63f2-864d-4696-b66e-9933ddb7c64e","order_by":5,"name":"Fatemeh Moshiri","email":"","orcid":"","institution":"Hormozgan University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Fatemeh","middleName":"","lastName":"Moshiri","suffix":""},{"id":609906333,"identity":"3503e20a-244c-4027-a370-cff5095c0b4d","order_by":6,"name":"Ensieh Salehi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+UlEQVRIiWNgGAWjYFAC5gZmBgMQzcDG8AFIs7ET1MKI0MI4A6SFmSgtEMDGzAO2loAG+faDjY8LCmzy5NuZjz22+bVNno+ZgfHDxxzcWgzOJDYbzzBIKzY4zJZunNt327CNmYFZcuY2PFoYEtukeQwOJ25g5jGTzu25zQjUwsbMi0eLfP/D9t88Bv8T5zfzf5O27LltT1ALw43ENmYegwOJDYd52KQZftxOJKjF4MbDZqDDkhM3HGYzk+xtuJ3cxszYjNcv8v3JBz/z/LFLnN9/+JnEjz+3bee3Nx/88BGfw1AAYxuYbCBWPQj8IUXxKBgFo2AUjBQAAL/aTI0cbK5DAAAAAElFTkSuQmCC","orcid":"","institution":"Hormozgan University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Ensieh","middleName":"","lastName":"Salehi","suffix":""}],"badges":[],"createdAt":"2026-02-14 06:56:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8877703/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8877703/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":105564432,"identity":"c939f57b-bc07-4e53-9950-c9ce0ba9e1c5","added_by":"auto","created_at":"2026-03-27 12:49:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1671438,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8877703/v1/2d583695-a8f7-42c1-9c73-1ab19c140526.pdf"},{"id":105228451,"identity":"e61bd7d7-5f7c-42a0-9491-50a525996fc6","added_by":"auto","created_at":"2026-03-23 17:12:45","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":414572,"visible":true,"origin":"","legend":"","description":"","filename":"Graphicalabstract.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8877703/v1/e3d07f63e81012c8188cafdb.jpg"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Benefits and Safety Profile of Laser-Assisted Zona Thinning in Frozen Cleavage-Stage Embryo Transfers: Evidence from 940 ICSI/FET Cycles","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTreatment with IVF/ICSI stands as the cornerstone of infertility treatment. Annually, approximately three million cycles of IVF/ICSI are carried out worldwide (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Despite significant advances in various aspects of IVF/ICSI, the process of embryo implantation still remains a critical factor limiting success rates(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The chance of conception is approximately 30% per embryo transfer and two-third of unsuccessful pregnancies attributed to challenges in implantation(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Implantation is a precisely orchestrated biological process that consists of embryo hatching, positioning, attachment, and invasion. Hatching is an essential step in the events leading to successful implantation and failure to hatch is one of the primary reasons for failure to implantation. During hatching, the embryo creates an opening through the zona barrier and exit into the uterine cavity where it implants into the receptive endometrium(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Prolonged in vitro culture, which can be aggravated by the process of freezing and thawing, has been demonstrated to have the potential to harden or thicken the ZP, affecting implantation (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Already late in the 20th century, it was shown that assisted hatching (AH), which involves artificial disruption of the ZP, could improve embryo implantation(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Mechanical partial zona dissection (PZD), use of acidic Tyrode\u0026rsquo;s solution, and laser are often used to achieve ZP destruction(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). However, the success rates following AH have considerably varied according to the patient population and the AH methods(\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Recently, the majority of reproductive centers have opted for laser-assisted hatching (LAH) due to its speed, safety, and precision(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). An updated Cochrane review indicated that LAH likely contributes to an increase in the clinical pregnancy rate (CPR), but its impact on miscarriage rate and live birth rate (LBR) remained inconclusive(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Another comprehensive analysis conducted across multiple centers in the US, using data from the National ART Surveillance System involving 35,518 cycles, revealed that LAH procedures were not linked to enhanced pregnancy outcomes(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite numerous randomized controlled trials (RCTs) on this topic, it is still unclear if LAH affects live birth rates (LBR) and neonatal outcomes, and, if so, for which age group it could work better. Therefore, this study aimed to determine the effect of laser assisted zona thinning on the clinical and neonatal outcomes of vitrified-thawed cleavage embryo transfers among patients of varying ages and diverse infertility etiologies.\u003c/p\u003e"},{"header":"Material and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy populations\u003c/h2\u003e \u003cp\u003e This retrospective, observational study was conducted at the infertility center of Hormozgan University of Medical Sciences in Bandar Abbas, Iran affiliated with Hormozgan University of Medical Sciences, bearing the ethical code IR.HUMS.REC.1402.319. Patients who underwent ICSI/ FET constituted the target population of this study. In total 940 eligible patients were divided into two groups, categorized by whether or not they received laser-assisted zona thinning. Within each group, patients were further divided into two subgroups based on age: \u0026lt;35 and \u0026ge;\u0026thinsp;35 years and by the specific causes of infertility.\u003c/p\u003e \u003cp\u003eThe exclusion criteria were as follows: (a) patients with severe uterine factors or chromosomal abnormalities (b) Fresh embryo transfer (c) day 5 embryo transfer, and (d) missing follow-up data. Ovarian stimulation, oocyte retrieval, fertilization and culture conditions were similar between groups.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEndometrial preparation regimen\u003c/h3\u003e\n\u003cp\u003eVitrified-warmed cleavage embryo transfer was performed following the artificial preparation of the endometrium with exogenous steroids. Briefly, patients were administered oral estradiol (E2) valerate at a dosage of 2mg/8h for 10\u0026ndash;12 days from the onset of menstruation. Upon ultrasound confirmation of an optimal endometrial thickness (\u0026ge;\u0026thinsp;7 mm with a triple-line pattern), estradiol valerate at the same dosage was sustained, and intramuscular administration of 50mg of progesterone commenced. Embryo transfer was scheduled on Day 4 following the start of progesterone treatment. Luteal phase support was maintained until 12th week of pregnancy or until the day of pregnancy test if negative.\u003c/p\u003e\n\u003ch3\u003eFreezing and thawing\u003c/h3\u003e\n\u003cp\u003eVitrification was performed using a Cryotop device and vitrification kit (KITAZATO BioPharma Co., Japan) following the manufacturer's instructions. Briefly, the embryos were transferred from the culture media to the equilibration solution (ES) for 7 min to restore their volume. Subsequently, they were transferred to a vitrification solution (VS) for 45\u0026ndash;60 s, ensuring complete replacement of the embryo's extracellular fluid with VS. Finally, embryos were loaded at the anterior end of Cryotop with extremely small amounts of VS and immediately immersed into liquid nitrogen.\u003c/p\u003e \u003cp\u003eThawing of vitrified embryos was conducted using a thaw kit (VT102, Kitazato Corporation). In short, the anterior end of the Cryotop containing embryos was immersed into the thawing solution (TS) for 1 minute. Then, the embryos were transferred to the base of the diluent solution (DS) for 3 minutes, underwent a 5-minute wash with washing solution (WS) for 5 minutes. Finally, they were transferred to the culture medium (Sage 1step, CooperSurgical, Denmark) and incubated for 3 hours at 37\u0026deg;C and 6% CO\u003csub\u003e2\u003c/sub\u003e.\u003c/p\u003e\n\u003ch3\u003eEmbryo selection and transfer\u003c/h3\u003e\n\u003cp\u003eThe post-thaw embryos were transferred at cleavage stage by the guidance of abdominal ultrasound. Two to four embryos were transferred, depending on the patient's age and embryo availability and quality.\u003c/p\u003e \u003cp\u003eEmbryos were graded as proposed by Depa-Martynow et al(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). This evaluation involved considering the number and quality of blastomeres, along with the percentage of fragmentation. The grading criteria were as follows: Grade A represented the highest quality, comprising embryos with a minimum of 7 blastomeres (7\u0026ndash;9 blastomeres) and cytoplasmic fragmentation of up to 20%. Grade B included embryos with 7\u0026ndash;9 blastomeres and cytoplasmic fragmentation exceeding 20%. Grade C encompassed 4\u0026ndash;6 cell embryos exhibiting cytoplasmic fragmentation up to 20%, while Grade D denoted the lowest quality, consisting of 4\u0026ndash;6 cell embryos with cytoplasmic fragmentation surpassing 20%(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eLaser-assisted zona thinning procedure\u003c/h3\u003e\n\u003cp\u003eThe laser-assisted hatching was carried out using the ZILOS tk Zone Infrared Laser Optical System (Hamilton Thorne Instruments Biosciences, Beverly, Massachusetts). Briefly, a 1480 nm invisible, in a computer-controlled non-contact laser diode beam, collimated and aligned with a 1-mW visible 670-nm diode laser aiming beam, entered an inverted microscope (Olympus IX71, Tokyo, Japan). It was guided through various mirrors and then focused by the microscope's \u0026times;40 objective lens. The power available at the objective's image plane was 47 milliwatts, yielding a maximum power density of 94 kW/cm\u003csup\u003e2\u003c/sup\u003e. The embryos were handled within their original culture medium in an embryo culture dish, positioned on the displacement stage of the diaphot inverted microscope. Each embryo was precisely situated within a region of the Zona Pellucida (ZP) at the targeted point of focus. Ensuring precision, the aiming spot was accurately positioned between the ZP's middle and outer edge. In order to reduce laser negative impacts, the target was placed at a specific area of the Zona Pellucida (ZP), ensuring a distinct separation between the inner ZP membrane and the blastomeres.\u003c/p\u003e \u003cp\u003eThe size of the aperture was controlled based on the duration of irradiation. In this study, one ablation lasting 2.8 ms was adequate to generate a defect of 12 \u0026micro;m in diameter. The laser operated at 100% power, three to five ablations of 2.8 ms were applied around a specific point on the Zona Pellucida (ZP) until 50\u0026ndash;60% of the total ZP thickness was affected. Importantly, the inner membrane of the ZP remained intact without complete breach. The AH procedure was carried out in approximately 20 s per embryo. Following the LAH procedure, to prevent potential toxicity from byproducts resulting from the laser's interaction with organic components of the Zona Pellucida (ZP), the embryos underwent a rinsing process. They were then transferred to a culture dish with 1ml sage 1 step (Cooper Surgical, Denmark) containing 10% serum protein substitute (SPS; Quinn\u0026rsquo;s; SAGE, USA) and cultured under of 6% CO2. All zona thinning procedures were conducted on the morning of D4, at least 1 hour before the embryo transfer.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eEndpoints\u003c/h2\u003e \u003cp\u003eThe main focus centered on the live birth rate (the number of deliveries that resulted in a live born neonate per transfer) as the primary outcome. Secondary outcomes included the biochemical pregnancy rate (defined by a pregnancy diagnosed only by the detection of beta hCG in serum per transfer), clinical pregnancy rate (determined by the visualization of at least one gestational sac in ultrasound examination per transfer), implantation rate ( defined as the percentage of gestational sacs of the total number of embryos transferred), miscarriage rate (expressed as the spontaneous loss of an intra-uterine pregnancy before 12 completed weeks of gestation). Additionally, neonatal aspects like preterm birth, malformation rate, and the sex of the baby, were considered.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) for continuous variables, and as frequencies and percentages for categorical variables, where appropriate. Comparisons of numerical variables between study groups were performed using the student\u0026rsquo;s t-test, while categorical variables were analyzed using the Chi-square (χ\u0026sup2;) test. A p-value less than 0.05 was considered statistically significant. All analyses were conducted with the Statistical Package for Social Sciences (SPSS) version 19.0 (SPSS Inc., USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 940 cryopreserved cleavage embryo transfer cycles conducted between September 2021 and February 2025 were included in this study. All patients were divided into two groups: 574 cases underwent laser-assisted zona thinning (LAZT), while 366 cases served as control group without laser-assisted zona thinning (non-LAZT).\u003c/p\u003e \u003cp\u003eThe mean age of patients was comparable in both groups (32.95\u0026thinsp;\u0026plusmn;\u0026thinsp;5.44 versus 32.44\u0026thinsp;\u0026plusmn;\u0026thinsp;5.68). No significant differences were observed in the BMI (26\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5 versus 26. 2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8) survival rate of the vitrified embryos after warming (97.0% versus 97.5%), the mean number of embryos transferred (3.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22 versus 2.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.46), and the number of high-quality transferred embryos (2.43 versus 2.42) between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In addition, the duration of infertility (5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29 versus 5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3) and endometrial thickness (8.22\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 versus 8.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98) did not significantly differ between the two groups (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of demographic, clinical and neonatal parameters between intervention (LAZT) group and control group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNo. of cycles\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e366\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e574\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale age (year, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.44\u0026thinsp;\u0026plusmn;\u0026thinsp;5.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.95\u0026thinsp;\u0026plusmn;\u0026thinsp;5.44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFemale BMI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of infertility (year, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.52\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.54\u0026thinsp;\u0026plusmn;\u0026thinsp;1.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEndometrial thickness (mm)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.22\u0026thinsp;\u0026plusmn;\u0026thinsp;1.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.15\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEmbryo survival (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97.50%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEmbryos transferred (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHigh-quality embryo transferred (n, %)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.42(85.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.43(84.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBiochemical pregnancy (%, n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e108/366(29.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e230/574(40.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical pregnancy (%, n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54/366(14.75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e138/574(24%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eImplantation (%, n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e63/1096 (5.75%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e180/1723 (10.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLive birth (%, n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51/366(14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e134/574(23.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNumber of live(n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.02*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMiscarriage (%, n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3/54(5.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/138(2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.37\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMultiple pregnancy (%, n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8/54(14.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35/138(25.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.01*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEctopic pregnancy (%, n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/54(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/138(0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBirth defect (%, n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0/51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0/134\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreterm birth (%, n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11/51(21.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43/134(32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePregnancy complication (%, n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2/51(3.92%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12/134(11.19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender (girl)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31/59(52.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e86/169(49.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender (boy)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28/59(47.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83/169(48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eContinuous variables (e.g., age, BMI, endometrial thickness, number of embryos transferred) were tested for normality using the Shapiro\u0026ndash;Wilk test. Normally distributed variables were summarized as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and compared between groups using the independent Student\u0026rsquo;s t-test. Categorical variables (e.g., biochemical pregnancy, clinical pregnancy, live birth, neonatal sex) were expressed as frequencies and percentages, and comparisons between groups were performed using the chi-square test or Fisher\u0026rsquo;s exact test when cell counts were \u0026lt;\u0026thinsp;5. Statistical significance was defined as P\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cb\u003e\\\u003c/b\u003e\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe biochemical pregnancy (40.1% versus29.5%), clinical pregnancy (24% versus 14.75%) and implantation rates (10.4% versus 5.75%) were significantly higher in the intervention group than in the control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The live birth rate (23.3% versus 14%), multiple pregnancy rates (25.3% versus 14.8%), and pregnancy complication (11.19% versus 3.92%) were also higher in the intervention group than the control group.\u003c/p\u003e \u003cp\u003eSubgroup analysis comparing the two groups in women aged less than 35 years and in women aged 35 years or more shows the higher biochemical pregnancy, clinical pregnancy, and live birth rate in women aged 35 years or more with laser-assisted hatching (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) compared to control group, while in women aged less than 35 years there were significant differences between control and intervention group in regard to multiple pregnancy and pregnancy complications. Moreover, the implantation rate and biochemical pregnancy showed a trend towards an increase in intervention group (11.2% versus 7%, p\u0026thinsp;=\u0026thinsp;0.08, and 43% versus 35.6%, p\u0026thinsp;=\u0026thinsp;0.07, respectively) compared to the control group.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSubgroup Analysis of Clinical and Neonatal Outcomes Based on Maternal Age\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl Group (Age\u0026thinsp;\u0026lt;\u0026thinsp;35) (n\u0026thinsp;=\u0026thinsp;213)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIntervention Group (Age\u0026thinsp;\u0026lt;\u0026thinsp;35) (n\u0026thinsp;=\u0026thinsp;402)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eControl Group (Age\u0026thinsp;\u0026ge;\u0026thinsp;35) (n\u0026thinsp;=\u0026thinsp;153)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIntervention Group (Age\u0026thinsp;\u0026ge;\u0026thinsp;35) (n\u0026thinsp;=\u0026thinsp;172)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003eClinical Outcomes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBiochemical Pregnancy, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (35.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e173 (43.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32 (20.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e57 (33.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.01*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical Pregnancy, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103 (25.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35 (20.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.04*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eImplantation Rate, % (n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.4 (47 / 633)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.2 (135 / 1207)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.5 (16 / 463)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.7 (45 / 516)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLive Birth, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (17.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100 (24.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13 (8.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e34 (19.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMiscarriage, % (n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.3 (3 / 41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0 (1 / 103)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.6 (3 / 35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMultiple pregnancy, % (n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.6 (6 / 41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.2 (27 / 103)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.4 (2 / 13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22.8 (8 / 35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNeonatal Outcomes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePreterm Birth, % (n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.1 (8 / 38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.0 (31 / 100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.1 (3 / 13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35.2 (12 / 34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePregnancy Complication, % (n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.6 (1 / 38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.0 (27 / 100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.002*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.7 (1 / 13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e35.3 (12 / 34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.02*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInfant Sex (Girl), % (n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48.8 (21 / 43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57.1 (72 / 126)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e62.5 (10 / 16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.6 (14 / 43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cb\u003e0.01*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eInfant Sex (Boy), % (n)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51.2 (22 / 43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42.9 (54 / 126)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.5 (6 / 16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e65.1 (28 / 43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.07\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eData are presented as n (%) unless otherwise specified. Statistical analysis was performed using the Chi-square test for categorical variables. A P value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe subgroup analysis based on the cause of infertility suggests that laser zona thinning may offer significant benefits in patients with PCOS and multiple factors infertility, particularly improving biochemical and live birth rates. Benefits in patients with poor ovarian reserve were also noted for biochemical pregnancy. However, no significant improvements were found in male factor, tubal factor, or unexplained infertility groups. Notably, pregnancy complications were increased in some intervention groups, warranting careful consideration in clinical practice (Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e \u0026amp; \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSubgroup Analysis of Clinical Outcomes Based on Infertility Etiology\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c8\" namest=\"c3\"\u003e \u003cp\u003eClinical Outcomes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBiochemical Pregnancy, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eClinical Pregnancy, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eImplantation Rate, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eLive Birth, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMiscarriage, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMultiple Pregnancy, n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eMale Factor (n\u0026thinsp;=\u0026thinsp;107)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;59)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (27.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (23.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.5 (15 / 177)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.1 (1 / 14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.1 (1 / 14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;48)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (35.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.6 (14 / 145)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (0 / 0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e16.7 (2 / 12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eTubal Factor (n\u0026thinsp;=\u0026thinsp;39)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;34)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (26.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.8 (6 / 104)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;5)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eUnexplained (n\u0026thinsp;=\u0026thinsp;152)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;84)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.8 (20 / 255)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e26.7 (4 / 15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;68)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (30.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.3 (19 / 204)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12 (17.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (0 / 0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e41.7 (5 / 12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003ePCOS (n\u0026thinsp;=\u0026thinsp;359)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;90)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13 (14.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.6 (15 / 268)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11 (12.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15.4 (2 / 13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e15.4 (2 / 13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;269)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e125 (46.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e77 (28.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.0 (97 / 807)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e73 (27.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.2 (4 / 77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e23.4 (18 / 77)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.02*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.04*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003ePoor Ovarian Response (n\u0026thinsp;=\u0026thinsp;245)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;77)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (18.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.7 (6 / 226)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 (6.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e20.0 (1 / 5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;168)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57 (40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e30 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.7 (39 / 504)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30 (17.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e23.3 (7 / 30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.01*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.87\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eMixed Factors (n\u0026thinsp;=\u0026thinsp;33)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;20)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.3 (1 / 61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1 (5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;13)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.9 (7 / 39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5 (38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e40.0 (2 / 5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e0.01*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eData are presented as n (%) unless otherwise specified. The denominator for percentage calculations is the number of cycles in the subgroup for primary outcomes (e.g., Live Birth) and the number of pregnancies for pregnancy-based outcomes (e.g., Miscarriage). \"\u0026mdash;\" indicates that a P value or percentage could not be calculated due to a zero value in one of the comparison groups (e.g., no clinical pregnancies). Statistical analysis was performed using the Chi-square test for categorical variables. A P value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eInterv., Intervention (LAZT) Group.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSubgroup Analysis of Neonatal Outcomes Based on Infertility Etiology\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eNeonatal Outcomes\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePreterm Birth, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePregnancy Complication, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eInfant Sex (Girl), n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eInfant Sex (Boy), n (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eMale Factor (n\u0026thinsp;=\u0026thinsp;107)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;59)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.7 (1 / 13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.7 (1 / 13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53.8 (7 / 13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46.2 (6 / 13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;48)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.7 (2 / 12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.0 (3 / 12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42.9 (6 / 14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e57.1 (8 / 14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eTubal Factor (n\u0026thinsp;=\u0026thinsp;39)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;34)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.7 (1 / 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e66.7 (4 / 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33.3 (2 / 6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;5)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eUnexplained (n\u0026thinsp;=\u0026thinsp;152)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;84)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.3 (5 / 15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.7 (1 / 15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55.0 (11 / 20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e45.0 (9 / 20)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;68)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.7 (5 / 12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41.7 (5 / 12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44.4 (8 / 18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e55.6 (10 / 18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.02*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003ePCOS (n\u0026thinsp;=\u0026thinsp;359)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;90)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.4 (4 / 11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46.2 (6 / 13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e53.8 (7 / 13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;269)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.6 (26 / 73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.5 (23 / 73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52.8 (47 / 89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e47.2 (42 / 89)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cb\u003e0.04*\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003ePoor Ovarian Response (n\u0026thinsp;=\u0026thinsp;245)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;77)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50.0 (3 / 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50.0 (3 / 6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;168)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.3 (10 / 30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.7 (8 / 30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50.0 (19 / 39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50.0 (19 / 39)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eMixed Factors (n\u0026thinsp;=\u0026thinsp;33)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eControl (n\u0026thinsp;=\u0026thinsp;20)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e100 (1 / 1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eInterv. (n\u0026thinsp;=\u0026thinsp;13)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.0 (2 / 5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.0 (2 / 5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e71.4 (5 / 7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e28.6 (2 / 7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eP value\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eData are presented as n (%) unless otherwise specified. The denominator for percentage calculations is the number of cycles in the subgroup for primary outcomes (e.g., Live Birth) and the number of pregnancies for pregnancy-based outcomes (e.g., Miscarriage). \"\u0026mdash;\" indicates that a P value or percentage could not be calculated due to a zero value in one of the comparison groups (e.g., no clinical pregnancies). Statistical analysis was performed using the Chi-square test for categorical variables. A P value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant. Interv., Intervention (LAZT) Group.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eMale Factor Subgroup\u003c/h2\u003e \u003cp\u003eIn the male factor subgroup, the intervention group (n\u0026thinsp;=\u0026thinsp;48) had a higher biochemical pregnancy rate (35.4% vs. 27.1%, P\u0026thinsp;=\u0026thinsp;0.36) and clinical pregnancy rate (25% vs. 23.7%, P\u0026thinsp;=\u0026thinsp;0.24) compared to the control group (n\u0026thinsp;=\u0026thinsp;59), though these differences were not statistically significant. The implantation rate was 9.6% in the intervention group versus 8.5% in the control group (P\u0026thinsp;=\u0026thinsp;0.49), with no significant difference observed. Live birth rates were 25% in the intervention group and 22% in the control group (P\u0026thinsp;=\u0026thinsp;0.28), showing no significant difference.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePCOS Subgroup\u003c/h2\u003e \u003cp\u003eIn patients with PCOS, the LAZT group (n\u0026thinsp;=\u0026thinsp;269) demonstrated significantly higher biochemical pregnancy (46.5% vs. 33.3%, P\u0026thinsp;=\u0026thinsp;0.02) and live birth rates (27.1% vs. 12.2%, P\u0026thinsp;=\u0026thinsp;0.04) compared to the control group (n\u0026thinsp;=\u0026thinsp;90). The clinical pregnancy rate was also higher in the intervention group (28.6% vs. 14.4%), though this difference approached but did not reach statistical significance (P\u0026thinsp;=\u0026thinsp;0.06).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePoor Ovarian Response Subgroup\u003c/h2\u003e \u003cp\u003eFor patients with poor ovarian response, the intervention group (n\u0026thinsp;=\u0026thinsp;168) showed a significantly higher biochemical pregnancy rate compared to controls (40.0% vs. 18.2%, P\u0026thinsp;=\u0026thinsp;0.01). While live birth rates were numerically higher in the LAZT group (17.9% vs. 6.5%), this difference was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.23).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eUnexplained Infertility Subgroup\u003c/h2\u003e \u003cp\u003eIn cases of unexplained infertility, no significant differences were observed between the intervention (n\u0026thinsp;=\u0026thinsp;68) and control (n\u0026thinsp;=\u0026thinsp;84) groups for biochemical pregnancy (30.9% vs. 42.9%, P\u0026thinsp;=\u0026thinsp;0.13), clinical pregnancy (17.6% vs. 17.9%, P\u0026thinsp;=\u0026thinsp;0.3), or live birth rates (17.6% vs. 17.9%, P\u0026thinsp;=\u0026thinsp;0.22). However, pregnancy complications were significantly higher in the intervention group (41.7% vs. 6.7%, P\u0026thinsp;=\u0026thinsp;0.02).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eMixed Factors Infertility Subgroup\u003c/h2\u003e \u003cp\u003eAmong patients with mixed infertility factors, the LAZT group (n\u0026thinsp;=\u0026thinsp;13) had a significantly higher biochemical pregnancy rate than the control group (53.8% vs. 15.0%, P\u0026thinsp;=\u0026thinsp;0.01). Live birth rates were also higher (38.5% vs. 5.0%), though this difference was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.31), likely due to the small sample size.\u003c/p\u003e \u003cp\u003eThe subgroup analysis based on the cause of infertility suggests that laser zona thinning may offer significant benefits in patients with PCOS and multiple factors infertility, particularly improving biochemical and live birth rates. Benefits in patients with poor ovarian reserve were also noted for biochemical pregnancy. However, no significant improvements were found in male factor, tubal factor, or unexplained infertility groups. Notably, pregnancy complications were increased in some intervention groups, warranting careful consideration in clinical practice (Tables\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e \u0026amp; \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe role of assisted hatching (AH) in ART remains a controversial issue in clinical practice. While some studies suggest potential benefits, others report no significant improvements in pregnancy outcomes particularly when it is applied universally in women who already have a good prognosis.\u003c/p\u003e \u003cp\u003eTo address this uncertainty, our study analyzed 940 ICSI/ FET cycles, comprising 574 with laser-assisted zona thinning (LAZT) and 366 controls. The results reveal that LAZT is associated with significantly improved biochemical, clinical pregnancy, implantation, live birth, and multiple pregnancy rates compared to non-LAZT in this population. However, LAZT is also associated with higher rate of pregnancy complications. Despite this, our findings suggest that LAZT treatment does not adversely affect neonatal outcomes.\u003c/p\u003e \u003cp\u003eThe zona pellucida (ZP) is a transparent, non-cellular glycoprotein layer that surrounds the plasma membrane of oocytes and early embryos. This specialized layer is essential for successful fertilization and early embryonic development. In a mature human oocyte, the ZP typically measures approximately 15\u0026ndash;18 \u0026micro;m in thickness. During natural embryo development, the ZP thins and eventually breaks down, allowing the blastocyst to hatch and implant into the uterine lining. This hatching process is essential for successful implantation and is typically completed by days 4 to 5 post-fertilization. However, in assisted reproductive technologies (ART), in vitro culture for extended periods and cryopreservation, can lead to ZP hardening. This hardening reduces the ZP's susceptibility to enzymatic degradation, making it more challenging for the embryo to hatch(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Consequently, embryos may face difficulties in escaping the ZP, potentially leading to implantation failure. To address this issue, techniques like AH are employed. In the late 1980s to early 2000s, various chemical and mechanical methods were explored for assisted hatching to address challenges in embryo implantation. But nowadays, the 1.48 \u0026micro;m infrared diode laser system has become the most widely utilized technique for AH in ART.\u003c/p\u003e \u003cp\u003eRecent evidence suggests that LAH is related to a higher clinical pregnancy rate, embryo implantation rate, and multiple pregnancy rate(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). However, LAH is unlikely to increase live birth rates(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In a large retrospective study, McLaughlin et al. found that LAH significantly reduced live birth rates in both good and poor prognosis patients undergoing fresh embryo transfer. The study reported a 4.7% lower live birth rate in the AH group compared to the control group(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In our study, obvious benefit on live birth rate was found when LAZT was used along with a vitrified cleavage embryo. Consistent with our findings, Endo et al. also reported that LAH substantially increased live birth rates in patients undergoing single vitrified blastocyst transfer(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). The discrepancy in outcomes may be attributed to differences in AH methodology used, extent of LAH, patient selection criteria, embryo quality assessment, the method of cryopreservation, ET type, the conception mode, the sample size, and study design.\u003c/p\u003e \u003cp\u003eLAH is considered a safe method in ART, as it does not adversely affect neonatal outcomes, including congenital malformations. In our study, we evaluated neonatal outcomes in all infants born following vitrified cleavage transfer with LAZT and compared them to all infants from a control group. Our findings revealed no significant differences between the two groups in terms of preterm birth, infant sex, or the incidence of congenital malformations in general population. These results suggest that LAH does not compromise neonatal health. However, our study identified an increased rate of pregnancy complications in the LAZT group. We hypothesized this may be related to the higher multiple pregnancy rate in the AH group underscoring the importance of careful patient selection and embryo transfer protocols to balance the benefits of LAH with the potential risks associated with multiple gestations.\u003c/p\u003e \u003cp\u003eWhile some studies have reported no significant differences in obstetric and neonatal outcomes following AH(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), others have observed higher rates of multiple pregnancies(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), which are associated with increased maternal and fetal risks.\u003c/p\u003e \u003cp\u003eOur sub-analyses suggest that LAH benefits are particularly evident in older women (\u0026ge;\u0026thinsp;35 years), in patients with PCOS or multifactorial infertility, and to some extent among those with poor ovarian reserve. One may have a concern about embryo quality between the LAH and control subgroups. To mitigate this potential bias, a rigorous grading and selection process was applied. An experienced embryologist assessed and selected embryos for transfer, ensuring that both comparable subgroups received embryos of similar quality. Moreover, it should be emphasized that all patients received the same freezing, thawing, and endometrial preparation protocols.\u003c/p\u003e \u003cp\u003ePrevious studies indicate that LAH can enhance embryo implantation by facilitating hatching, particularly in challenging cases such as advanced maternal age or patients with repeated implantation failure(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). For instance, Ghannadi et al. found that in women\u0026thinsp;\u0026ge;\u0026thinsp;35 years, LAH significantly increased both chemical pregnancy (30.12% vs 18.96%) and clinical pregnancy rates (27.71% vs 16.37%) compared to no LAH(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). A recent retrospective analysis for vitrified-warmed embryo transfers also suggests that in women\u0026thinsp;\u0026gt;\u0026thinsp;40, LAH may improve pregnancy outcomes(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). With increasing age, the zona pellucida is thought to become harder or less penetrable, possibly due to increased cross-linking or changes in zona glycoproteins. In parallel, embryo competence tends to decline with age, which can impede natural hatching. Thus, when fewer high-quality embryos are available, interventions like LAH may increase the likelihood that the embryos present will successfully implant. Regarding the etiology of infertility, the majority of patients appear to benefit from AH, with the effect being more pronounced in individuals with PCOS or multifactorial infertility. While the precise mechanisms remain to be fully elucidated, several factors may explain its efficacy in these populations. In PCOS, hormonal imbalances can lead to reduced endometrial receptivity, hindering embryo implantation. Additionally, despite a higher number of oocytes retrieved, their quality may be compromised, resulting in embryos less capable of successful implantation.\u003c/p\u003e \u003cp\u003eIn contrast, patients with multifactorial infertility often experience combined factors affecting implantation, and AH may help overcome one of the potential barriers to successful implantation.\u003c/p\u003e \u003cp\u003eThis study has several limitations. As a retrospective, single-center observational analysis without randomization, it is subject to potential selection bias and unmeasured confounding. The transfer of multiple embryos increases the likelihood of multiple gestations, which may independently influence pregnancy complications and makes it difficult to fully isolate the effect of LAZT. Some subgroup analyses, particularly those involving rare outcomes such as congenital anomalies, were limited by small sample sizes and may be underpowered. Additionally, the study lacked information on embryo chromosomal status, including aneuploidy, which is an important determinant of implantation and pregnancy outcomes. Without genetic data, it remains unclear whether the observed differences reflect the effect of LAZT itself or variations in underlying embryo viability.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur findings suggest that LAZT may improve clinical outcomes across the general population, with more pronounced benefits observed in patients aged \u0026ge;35 years and those with PCOS or multiple infertility factors. While LAZT does not appear to adversely affect neonatal health, the increased multiple pregnancy rate and associated complications necessitate careful patient selection and counseling. Further research is warranted to confirm these findings and optimize assisted hatching protocols to minimize associated risks.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003eMAK: Data collection, embryology procedures, data analysis, writing – original draft.SH: Clinical data collection, patient management, literature review, manuscript editing.FF: Statistical analysis, data interpretation, manuscript revision.ZM: Data coordination, patient follow-up, preparation of tables and figures.EN: Laboratory procedures, embryo handling, data quality control.FM: Clinical data verification, contribution to discussion, and interpretation.ES: Study conception and design, supervision, data interpretation, and final approval of the manuscript.All authors have reviewed and approved the final manuscript and agree to be accountable for its content.\u003c/p\u003e\n\u003ch2\u003eAcknowledgement\u003c/h2\u003e\n\u003cp\u003eThe authors would like to express their sincere gratitude to the staff of the Fertility and Infertility Research Center at Hormozgan University of Medical Sciences for their invaluable technical and clinical support throughout this study. We also extend our appreciation to the embryology and nursing teams for their dedication in patient care and laboratory procedures. We thank all patients who generously agreed to participate in this research. Their cooperation made this study possible. Finally, we acknowledge the Hormozgan University of Medical Sciences for providing institutional support for this project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol received approval from the Institutional Review Board of Hormozgan University of Medical Sciences (approval ID: IR.HUMS.REC.1402.319).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all individual participants included in the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChambers GM, Dyer S, Zegers-Hochschild F, de Mouzon J, Ishihara O, Banker M et al (2021) International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology, 2014. Hum Reprod 36(11):2921\u0026ndash;2934\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDe Geyter C, Calhaz-Jorge C, Kupka MS, Wyns C, Mocanu E, Motrenko T et al (2020) ART in Europe, 2015: results generated from European registries by ESHRE. Hum Reprod open 2020(1):hoz038\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim S-M, Kim J-S (2017) A review of mechanisms of implantation. Dev Reprod 21(4):351\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKutlu P, Atvar O, Vanlioglu OF (2010) Laser assisted zona thinning technique has no beneficial effect on the ART outcomes of two different maternal age groups. J Assist Reprod Genet 27:457\u0026ndash;461\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRicardo Loret de Mola J, Garside WT, Bucci J, Tureck RW, Heyner S (1997) Analysis of the human zona pellucida during culture: correlation with diagnosis and the preovulatory hormonal environment. J Assist Reprod Genet 14:332\u0026ndash;336\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eElnahas T, Tawab N, Azmy O, Elnoury A, El-Faissal Y, Fouad T et al (2017) Prospective randomized trial on the use of laser assisted hatching for transfer of frozen/thawed embryos in human Intracytoplasmic Sperm injection. Middle East Fertility Soc J 22(4):309\u0026ndash;312\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCohen J, Elsner C, Kort H, Malter H, Massey J, Mayer MP et al (1990) Impairment of the hatching process following IVF in the human and improvement of implantation by assisting hatching using micromanipulation. Hum Reprod 5(1):7\u0026ndash;13\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBalaban B, Urman B, Alatas C, Mercan R, Mumcu A, Isiklar A (2002) A comparison of four different techniques of assisted hatching. Hum Reprod 17(5):1239\u0026ndash;1243\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMagli M, Gianaroli L, Ferraretti A, Fortini D, Aicardi G, Montanaro N (1998) Rescue of implantation potential in embryos with poor prognosis by assisted zona hatching. Hum Reprod (Oxford England) 13(5):1331\u0026ndash;1335\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei C, Xiang S, Liu D, Wang C, Liang X, Wu H et al (2023) Laser-assisted hatching improves pregnancy outcomes in frozen-thawed embryo transfer cycles of cleavage-stage embryos: a large retrospective cohort study with propensity score matching. J Assist Reprod Genet 40(2):417\u0026ndash;427\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLacey L, Hassan S, Franik S, Seif MW, Akhtar MA Assisted hatching on assisted conception (in vitro fertilisation (IVF) and intracytoplasmic sperm injection (ICSI)). Cochrane Database Syst Reviews. 2021(3).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKissin DM, Kawwass JF, Monsour M, Boulet SL, Session DR, Jamieson DJ et al (2014) Assisted hatching: trends and pregnancy outcomes, United States, 2000\u0026ndash;2010. Fertil Steril 102(3):795\u0026ndash;801\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDepa-Martynow M, Jedrzejczak P, Pawelczyk L (2007) Pronuclear scoring as a predictor of embryo quality in in vitro fertilization program. Folia Histochem Cytobiol 45(I):85\u0026ndash;89\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMasoudi M, Yamini N, Salehi F, Aflatoonian R, Kutenaee MA, Esfandiyari S et al (2021) Notch signaling pathway in cumulus cells reflecting zygote and embryo quality in polycystic ovary syndrome. Arch Gynecol Obstet 304:1097\u0026ndash;1105\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarroll J, Depypere H, Matthews C (1990) Freeze\u0026ndash;thaw-induced changes of the zona pellucida explains decreased rates of fertilization in frozen\u0026ndash;thawed mouse oocytes. Reproduction 90(2):547\u0026ndash;553\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng M, Su S, Li L (2018) The effect of laser-assisted hatching on pregnancy outcomes of cryopreserved-thawed embryo transfer: a meta-analysis of randomized controlled trials. Lasers Med Sci 33(3):655\u0026ndash;666\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcLaughlin JE, Choi BY, Liu Q, Gelfond JA, Robinson RD, Chang TA et al (2019) Does assisted hatching affect live birth in fresh, first cycle in vitro fertilization in good and poor prognosis patients? J Assist Reprod Genet 36(12):2425\u0026ndash;2433\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEndo Y, Mitsuhata S, Hayashi M, Fujii Y, Motoyama H (2021) Laser-assisted hatching on clinical and neonatal outcomes in patients undergoing single vitrified Blastocyst transfer: A propensity score\u0026ndash;matched study. Reproductive Med Biology 20(2):182\u0026ndash;189\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi D, Yang D-L, An J, Jiao J, Zhou Y-M, Wu Q-J et al (2016) Effect of assisted hatching on pregnancy outcomes: a systematic review and meta-analysis of randomized controlled trials. Sci Rep 6(1):31228\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu X, Liu Y, Cao X, Liu S-Y, Dong X (2019) Laser-assisted hatching and clinical outcomes in frozen-thawed cleavage-embryo transfers of patients with previous repeated failure. Lasers Med Sci 34(6):1137\u0026ndash;1145\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhannadi A, Kazerooni M, Jamalzadeh F, Amiri S, Rostami P, Absalan F (2011) The effects of laser assisted hatching on pregnancy rates. Iran J reproductive Med 9(2):95\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanoi R, Ramakrishnan S, Mondal S, Gutgutia R (2023) P-230 Does laser-assisted hatching improve pregnancy rates: a retrospective analysis. Hum Reprod 38(Supplement1):dead093\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Laser-assisted zona thinning, pregnancy outcomes, assisted reproductive technology (ART), embryo implantation","lastPublishedDoi":"10.21203/rs.3.rs-8877703/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8877703/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLaser-assisted zona thinning (LAZT) has been proposed to enhance embryo implantation by facilitating zona pellucida (ZP) hatching. This retrospective study evaluates the impact of LAZT on clinical and neonatal outcomes in vitrified-warmed cleavage-stage embryo transfers. A total of 940 patients undergoing ICSI/FET between September 2021 and February 2025 were analyzed. Patients were divided into two groups: 574 underwent LAZT, and 366 served as controls. Subgroup analyses were performed based on age (\u0026lt;\u0026thinsp;35 and \u0026ge;\u0026thinsp;35 years) and infertility etiology. The LAZT group exhibited significantly higher biochemical pregnancy (40.1% vs. 29.5%), clinical pregnancy (24% vs. 14.75%), implantation (10.4% vs. 5.75%), and live birth rates (23.3% vs. 14%) compared to controls (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). No significant differences were observed in neonatal outcomes such as preterm birth, infant sex, or the presence of congenital malformations. Notably, women aged\u0026thinsp;\u0026ge;\u0026thinsp;35 years showed more pronounced benefits in biochemical and live birth rates. Patients with polycystic ovary syndrome and multiple infertility factors also demonstrated improved outcomes. However, increased pregnancy complications (11.19% vs 3.92%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01) were observed in the LAZT group, necessitating cautious clinical application.\u003c/p\u003e","manuscriptTitle":"Clinical Benefits and Safety Profile of Laser-Assisted Zona Thinning in Frozen Cleavage-Stage Embryo Transfers: Evidence from 940 ICSI/FET Cycles","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-23 17:12:34","doi":"10.21203/rs.3.rs-8877703/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-05T02:37:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-28T18:21:31+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-27T12:29:08+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-21T14:39:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"53720139158749880269239858921370072822","date":"2026-03-20T21:48:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"146423649421475291358597431798125137356","date":"2026-03-19T04:44:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"977319177153992504341095519839963594","date":"2026-03-19T03:02:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-19T02:50:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-01T18:46:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-28T10:55:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"Lasers in Medical Science","date":"2026-02-14T06:40:04+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"lasers-in-medical-science","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"lims","sideBox":"Learn more about [Lasers in Medical Science](https://link.springer.com/journal/10103)","snPcode":"10103","submissionUrl":"https://submission.springernature.com/new-submission/10103/3","title":"Lasers in Medical Science","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"90dbf540-fc8b-4fa5-970b-1b06aba7e19f","owner":[],"postedDate":"March 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-05T02:53:35+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-23 17:12:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8877703","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8877703","identity":"rs-8877703","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}