Previous In Vitro Fertilization Attempts Research Articles

Co-administration of GnRH-agonist and hCG (double trigger) for final oocyte maturation increases the number of top-quality embryos in patients undergoing IVF/ICSI cycles

BackgroundThe utilization of a double trigger, involving the co-administration of gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) for final oocyte maturation, is emerging as a novel approach in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during controlled ovarian hyperstimulation (COH). This protocol involves administering GnRH-a and hCG 40 and 34 h prior to ovum pick-up (OPU), respectively. This treatment modality has been implemented in patients with low/poor oocytes yield. This study aimed to determine whether the double trigger could improve the number of top-quality embryos (TQEs) in patients with fewer than three TQEs.MethodsThe stimulation characteristics of 35 in vitro fertilization (IVF) cycles were analyzed. These cycles were triggered by the combination of hCG and GnRHa (double trigger cycles) and compared to the same patients’ previous IVF attempt, which utilized the hCG trigger (hCG trigger control cycles). The analysis involved cases who were admitted to our reproductive center between January 2018 and December 2022. In the hCG trigger control cycles, all 35 patients had fewer than three TQEs.ResultsPatients who received the double trigger cycles yielded a significantly higher number of 2PN cleavage embryos (3.54 ± 3.37 vs. 2.11 ± 2.15, P = 0.025), TQEs ( 2.23 ± 2.05 vs. 0.89 ± 0.99, P < 0.001), and a simultaneously higher proportion of the number of cleavage stage embryos (53.87% ± 31.38% vs. 39.80% ± 29.60%, P = 0.043), 2PN cleavage stage embryos (43.89% ± 33.01% vs. 27.22% ± 27.13%, P = 0.014), and TQEs (27.05% ± 26.26% vs. 14.19% ± 19.76%, P = 0.019) to the number of oocytes retrieved compared with the hCG trigger control cycles, respectively. The double trigger cycles achieved higher rates of cumulative clinical pregnancy (20.00% vs. 2.86%, P = 0.031), cumulative persistent pregnancy (14.29% vs. 0%, P < 0.001), and cumulative live birth (14.29% vs. 0%, P < 0.001) per stimulation cycle compared with the hCG trigger control cycles.ConclusionCo-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) may be suggested as a valuable new regimen for treating patients with low TQE yield in previous hCG trigger IVF/intracytoplasmic sperm injection (ICSI) cycles.

P-664 Insulin-like peptide 3 as a potential biomarker in predicting IVF success and ovarian reserve in women with unexplained infertility and diminishing ovarian reserve

Abstract Study question Could insulin-like peptide 3 (INSL3) predict ovarian reserve and in vitro fertilization (IVF) success in women with unexplained infertility (UI) and diminishing ovarian reserve (DOR)? Summary answer In women with DOR, reduced intrafollicular and serum INSL3 levels correspond with low AMH and high FSH levels, similar to established ovarian reserve markers. What is known already INSL3, belonging to the insulin-like peptide family, is produced by theca interna cells within antral follicles and the corpora lutea. It is hypothesized that INSL3 is integral to the initial development and function of antral follicles, specifically through its regulatory effect on androgen biosynthesis in the thecal cells of these follicles. Moreover, INSL3 is implicated in the modulation of the ovarian microenvironment, which is essential for facilitating the maturation of oocytes. Study design, size, duration This research was carried out at the IVF centers of two tertiary university hospitals, assessing 49 infertile women with either UI (n = 24) or DOR (n = 25) during IVF treatment. A control group (n = 26) comprised women with normal ovarian reserve undergoing IVF due to male or tubal factors. Outcome parameters are ovarian reserve markers (serum FSH, estradiol, AMH, INSL3 concentration and antral follicle count [AFC]), positive pregnancy rate and live birth rate (LBR) (gestational age ≥28 weeks). Participants/materials, setting, methods Women aged between 20-40 with a body mass index (BMI)&amp;lt;30 kg/m² were included. Serum FSH, estradiol, AMH, INSL3 levels and AFC were evaluated on menstrual cycle days 2 or 3, and INSL3 in follicular fluid from dominant follicles (&amp;gt;14 mm) were evaluated during oocyte retrieval. Exclusions included endocrine abnormalities (e.g., polycystic ovary syndrome, hyperprolactinemia, hypo and hyperthyroidism) cycle cancellation due to lack of a viable embryo, uncorrected Mullerian anomalies, recurrent miscarriage history and hydrosalpinx presence. Main results and the role of chance The mean age in the study groups was 28.41±3.5 (UI), 32.40±4.21 (DOR), and 29.65±3.91 (control). In the DOR group, female age (p = 0.001), BMI (p = 0.049), duration of infertility (p = 0.006), previous IVF attempts (p &amp;lt; 0.001), basal FSH (p &amp;lt; 0.001), and basal estradiol (p &amp;lt; 0.001) were higher, while AMH (p &amp;lt; 0.001), AFC (p &amp;lt; 0.001), and follicular fluid INSL3 (p &amp;lt; 0.001) were lower. Serum INSL3 in DOR was lower but not statistically significant. No correlation was found between serum INLS, follicular fluid INSL3, ovarian reserve markers, positive pregnancy rates, miscarriage, and LBR. DOR group had longer stimulation durations (p = 0.017), but lower max estradiol (p &amp;lt; 0.001), fewer oocytes (p &amp;lt; 0.001), mature follicles (p &amp;lt; 0.001), and PN (p &amp;lt; 0.001). Pregnancy rates were 54.1% (UI), 24% (DOR), and 53.84% (control); LBRs were 54.1% (UI), 20% (DOR), and 42.3% (control), with significant differences in pregnancy tests (p = 0.04) and LBR (p = 0.03), both lower in DOR. Univariate analysis identified duration of infertility (p = 0.019) and basal FSH (p = 0.009) as significant LBR predictors. Multivariable analysis confirmed basal FSH (p = 0.033) as significant, with increased duration of infertility and basal FSH level reducing LBR probability. Limitations, reasons for caution The limited sample size of our study potentially undermines the robustness of circulating INSL3 as a predictive biomarker for DOR, evidenced by the non-significant decrease in serum INSL3 levels in the DOR group. Moreover, the lack of INSL3 level assessment during oocyte retrieval further constrains our findings. Wider implications of the findings Our research explored INSL3 as a viable biomarker for predicting ovarian reserve and IVF success in UI and DOR cases. Reduced INSL3 levels in circulation and follicular fluid in DOR patients could be beneficial in clinical practice. Trial registration number not applicable

Predicting personalized cumulative live birth rate after a complete in vitro fertilization cycle: an analysis of 32,306 treatment cycles in China

BackgroundThe cumulative live birth rate (CLBR) has been regarded as a key measure of in vitro fertilization (IVF) success after a complete treatment cycle. Women undergoing IVF face great psychological pressure and financial burden. A predictive model to estimate CLBR is needed in clinical practice for patient counselling and shaping expectations.MethodsThis retrospective study included 32,306 complete cycles derived from 29,023 couples undergoing IVF treatment from 2014 to 2020 at a university-affiliated fertility center in China. Three predictive models of CLBR were developed based on three phases of a complete cycle: pre-treatment, post-stimulation, and post-treatment. The non-linear relationship was treated with restricted cubic splines. Subjects from 2014 to 2018 were randomly divided into a training set and a test set at a ratio of 7:3 for model derivation and internal validation, while subjects from 2019 to 2020 were used for temporal validation.ResultsPredictors of pre-treatment model included female age (non-linear relationship), antral follicle count (non-linear relationship), body mass index, number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, tubal factor, male factor, and scarred uterus. Predictors of post-stimulation model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), number of previous IVF attempts, number of previous embryo transfer failure, type of infertility, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. Predictors of post-treatment model included female age (non-linear relationship), number of oocytes retrieved (non-linear relationship), cumulative Day-3 embryos live-birth capacity (non-linear relationship), number of previous IVF attempts, scarred uterus, stimulation protocol, as well as endometrial thickness, progesterone and luteinizing hormone on trigger day. The C index of the three models were 0.7559, 0.7744, and 0.8270, respectively. All models were well calibrated (p = 0.687, p = 0.468, p = 0.549). In internal validation, the C index of the three models were 0.7422, 0.7722, 0.8234, respectively; and the calibration P values were all greater than 0.05. In temporal validation, the C index were 0.7430, 0.7722, 0.8234 respectively; however, the calibration P values were less than 0.05.ConclusionsThis study provides three IVF models to predict CLBR according to information from different treatment stage, and these models have been converted into an online calculator (https://h5.eheren.com/hcyc/pc/index.html#/home). Internal validation and temporal validation verified the good discrimination of the predictive models. However, temporal validation suggested low accuracy of the predictive models, which might be attributed to time-associated amelioration of IVF practice.

Letrozole cotreatment improves the follicular output rate in high-body-mass-index women with polycystic ovary syndrome undergoing IVF treatment.

Women who have polycystic ovary syndrome (PCOS) with high body mass index (BMI) typically have an attenuated ovarian response and decreased follicular size, which are linked to unfavourable clinical outcomes following in vitro fertilization (IVF) therapy. The follicular output rate (FORT), a qualitative indicator of follicular response, seems to be positively linked to the clinical outcomes of IVF. Progestin-primed ovarian stimulation (PPOS) has become an alternative to gonadotropin-releasing hormone (GnRH) analogues to inhibit the premature luteinizing hormone (LH) surge. As letrozole (LE) shows promise in enhancing ovarian response, we compared PPOS with and without LE for PCOS in high BMI women with a focus on the FORT and associated clinical and pregnancy outcomes. For the recruited 1508 women, ten variables including AFC; age; basal sex hormone level; BMI; infertility type; period of infertility and number of previous IVF attempts were chosen in the propensity score matching (PSM) model to match 1374 women who taken the MPA+ hMG protocol with 134 women who received the MPA+ hMG+ LE treatment at a 1:1 ratio. FORT was selected as the primary outcome measure. The number of oocytes retrieved, viable embryos, hMG dosage, duration, oocyte maturity rate, fertilization rate, and implantation rate were established as secondary outcomes. FORT was substantially elevated in the MPA+hMG+LE group compared with the MPA+hMG group (61% [35%, 86%] vs. 40% [25%, 60%], P <.001). Interestingly, the LE cotreatment group had a considerably lower mature oocyte rate despite having a similar number of mature oocytes and embryos recovered. The average hMG dosages and durations in the study group were similar to those in the control group. The implantation rate in the study group was numerically higher but without statistic significant than that in the control groups (43.15% (107/248) vs. 38.59% (115/298), OR 1.008, 95% CI 0.901-1.127; P >.05). The effect of LE combined with PPOS on FORT is better than the effect of the standard PPOS treatment in women with PCOS and a high BMI, but there is no substantially beneficial impact on pregnancy outcomes or the cycle features of COS, including consumption of hMG.

First pilot study of maternal spindle transfer for the treatment of repeated in vitro fertilization failures in couples with idiopathic infertility

To gain insights into the technical feasibility of maternal spindle transfer (MST) applied in the context of repeated invitro fertilization (IVF) failures for the treatment of idiopathic infertility. A prospective pilot study. IVF center. Twenty-five infertile couples with multiple previous unsuccessful IVF cycles (range, 3-11), no previous pregnancy, and no history of mitochondrial DNA (mtDNA) disease participated. The study focused on women <40 years, with previous IVF attempts characterized by a pattern of low fertilization rates and/or impaired embryo development. Couples with severe male-factor infertility were not eligible. Oocyte donors with previous successful IVF outcomes were matched with patients according to standard practice. We performed MST by transferring metaphase II spindles from the patients' oocytes into the previously enucleated donor oocytes, followed by intracytoplasmic sperm injection, invitro embryo culture, blastocyst biopsy, and vitrification. Only euploid blastocysts were considered for embryo transfer. Outcome measures included oocyte fertilization, blastocyst development, clinical pregnancy and live birth, incidence of mitochondrial carryover and potential mtDNA reversal, as well as general health of the children born. Twenty-eight MST cycles produced 6 children (19 embryo transfers, 7 clinical pregnancies). Pediatric follow-up of the children, performed at intervals from birth to 12-24 months of age, revealed their development to be unremarkable. DNA fingerprinting confirmed that the nuclear DNA of MST children was inherited from both parents, without any contribution from the oocyte donor. For 5 of the children, mtDNA was derived almost exclusively (>99%) from the donor. However, 1 child, who had similarly low mtDNA carryover (0.8%) at the blastocyst stage, showed an increase in the maternal mtDNA haplotype, accounting for 30% to 60% of the total at birth. This pilot study provides the first insights into the feasibility of applying MST for patients with idiopathic infertility and repeated IVF failures. Reconstructed oocytes produced embryos capable of implanting, developing to term and producing apparently healthy newborns/children. However, claims concerning the efficacy of MST with respect to infertility treatment would be premature considering the limitations of this study. Importantly, mtDNA reversal was detected in one child born after MST, a finding with possible implications for mitochondrial replacement therapies. Pilot trial registry number, ISRCTN11455145. The date of registration: 20/02/2018. The date of enrolment of the first patients: 18/03/2018.

P–674 Development of a predictive model indicating the population of poor responders benefiting from luteal phase oocyte retrieval

Abstract Study question Can successful implementation of luteal phase oocyte retrieval (LuPOR) following conventional follicular phase oocyte retrieval (FoPOR) be predicted for poor ovarian response (POR) patients? Summary answer Antral follicle count (AFC), number of small follicles recorded in FoPOR, and estradiol (E2) levels on FoPOR and LuPOR trigger days, predict successful LuPOR application. What is known already A second follicular wave in the same menstrual cycle was first observed in domestic animals such as horses and cattle and thenceforth in women. The second follicular wave has been introduced as an encouraging means towards optimizing the context of in vitro fertilization (IVF) success rates for infertile women and especially for POR patients. Double ovarian stimulation coupled with two oocyte retrievals in the same menstrual cycle has been proposed, and encouraging results have been reported. However, the high heterogeneity characterizing POR patients dictates that studies should focus on factors indicating efficient LuPOR application. Study design, size, duration This retrospective observational study included 1688 women diagnosed with POR, undergoing natural IVF cycles between 2012–2020 including two oocyte retrievals in the same menstrual cycle. Patients’ age, body mass index (BMI), number of previous POR incidences, basal hormonal levels, AFC, E2 evaluated on both trigger days and number of small follicles (8–13 mm) were evaluated on their predictive power regarding retrieval of at least one MII oocyte following LuPOR, being regarded as successful LuPOR implementation. Participants/materials, setting, methods A diagnosis of POR according to Bologna criteria served as the inclusion criterion for this single center study. All other infertility etiologies were excluded. Patient dataset was stratified according to age in quantiles. A random 20% of each quantile was employed to validate the model. The remaining 80% was employed to develop this model. The predictive value was determined employing the Area Under the Curve (AUC) of the Receiver Operating Characteristics, employing Youden’s index. Main results and the role of chance Patients’ age, BMI, number of previous failed IVF attempts, basal levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin and progesterone failed to be predictive of a successful LuPOR as the AUC was below 0.6. AFC with a threshold value of 4.47, was found to be predictive of an effective LuPOR with an AUC of 0.86, sensitivity 0.8, specificity 0.75, and accuracy 0.79. E2 levels evaluated on the FoPOR trigger day, with a threshold value of 232.66 pg/ml, were similarly predictive of an effective LuPOR presenting with an AUC 0.86, specificity 0.75, sensitivity 0.86 and accuracy 0.82. Similarly, E2 evaluated on the LuPOR trigger day, with a threshold value of 200.89 pg/ml, presented with an AUC 0.89, specificity 0.85, sensitivity 0.95 and accuracy 0.92. The number of small follicles during FoPOR also appeared to be predictive of the presence of at least one MII oocyte during LuPOR, with a threshold value of 2.94. The AUC was 0.82, specificity 0.75, sensitivity 0.76 and accuracy 0.75. When combining the above characteristics into a single predictive model the AUC was 0.88, specificity 0.73, sensitivity 0.94 and accuracy 0.89. The positive and negative predictive value of the model were 93.5% and 46.8%, respectively. Limitations, reasons for caution Employment of natural cycles may present as a limitation when examining the value of this study, as the cut-off values reported herein may be altered when stimulation is employed. Since internal validation may be confounded by the fact that this was a single center study, external validation is required. Wider implications of the findings: The clinical end-point of this study reporting back to the practitioner, is the development of a predictive model identifying the optimal POR population for whom LuPOR practice is valuable. The high positive predictive value of this model may assist clinicians in identifying poor responders who will benefit from this approach. Trial registration number Not applicable

Does the use of microfluidic sperm sorting for the sperm selection improve in vitro fertilization success rates in male factor infertility?

To evaluate the clinical outcome of assisted reproductive technology (ART) cycles in couple with male infertility, where the spermatozoa were selected using either a conventional gradient-density centrifugation technique or microfluidic sperm sorting. A total of 181 patients who underwent in vitro fertilization (IVF) because of male factor infertility at the IVF center of Bezmialem and Yeditepe University Hospital were included in this study. All patients were divided into two groups according to the sperm selection method: group I (n = 91): microfluidic sperm-sorting chip; group II (n = 90): density-gradient centrifugation. Data collected included male and female age, type of infertility, duration of infertility, previous IVF attempts, smoking, antral follicle count, total dosage of gonadotropins, maximum estradiol levels, duration of stimulations, endometrial thickness on human chorionic gonadotropin day, total number of oocytes retrieved, number of mature oocytes retrieved, number of pronuclear (PN), sperm parameters, clinical PR and ongoing PR. There was no statistically significant difference in clinical PR and ongoing PR between groups (49.5% vs 40%, P = 0.2; 44% vs 36.7%, P = 0.3; respectively). The improvement in pregnancy rate was more prominent in patients where the female partner's age is higher than 35 (P = 0.09) and men have a total motile sperm count between 1 and 5 million (P < 0.01). Microfluidic devices, "labs-on-a-chip," are a disposable, easy to use, and inexpensive method for sperm sorting. Our results show that IVF success rates might improve with the use of a microfluidic sperm-sorting chip for sperm selection in male infertility.

MON-LB003 Clinical Case Series of Augmented Fertility in Females After Administration of an Amino Acid Blend That Enhances Release of Human Growth Hormone

Supplementation with adjuvant therapies, including growth hormone (hGH), is commonly used to improve fertility treatment outcomes. hGH is important for normal female fertility; low hGH has been associated with causes of infertility and impaired fertility, including polycystic ovarian syndrome (PCOS), endometriosis, diminished ovarian reserve (DOR), and advanced maternal age. A novel, low dose, orally administered amino acid blend has been previously shown in a double-blind, randomized, placebo-controlled, crossover clinical trial to produce a statistically significant increase in endogenous hGH secretion. In this clinical case series, we report outcomes in 7 women with infertility or impaired fertility and conditions associated with low hGH who administered the amino acid blend during fertility treatment (n=5) or timed intercourse/spontaneous pregnancy (n=2). Medical history included conditions associated with impaired fertility and low hGH: endometriosis (n=3), PCOS (n=2), and poor response to ovarian stimulation/history of failed in vitro fertilization (IVF) (n=3). The amino acid blend (containing 2.9 g of L-lysine, L-arginine, oxo-proline, N-acetyl-L-cysteine, L-glutamine, and schizonepeta) was administered daily on an empty stomach. Outcomes included embryo quality and success of embryo transfer (for IVF) and successful pregnancy/live births. Mean±SD age was 33±5 years (range 27-38) and BMI was 27±7 kg/m2 (range 21-37). Time to pregnancy ranged from 1 week to 9 months (median 3 months) prior to egg retrieval for IVF (n=4), intrauterine insemination (n=1), or timed intercourse/spontaneous pregnancy (n=2). For women with a history of failed IVF (n=3), there was an improvement in oocyte retrieval, a higher fertilization rate, and a greater number of high-quality embryos compared to previous IVF attempts. There were 2 twin pregnancies (both following IVF). All 7 pregnancies resulted in live births. Consistent with previous studies, the amino acid blend was well tolerated; no adverse events were observed. We report a case series of successful pregnancy in 7 women with conditions associated with low hGH including PCOS, endometriosis, and poor response to ovarian stimulation/history of failed IVF who administered the amino acid blend concomitant with fertility treatment or who reported spontaneous pregnancy. This may represent a potential low-risk and cost-effective treatment to improve IVF success and increase pregnancy rates in individuals with infertility or impaired fertility.

Couples with mild male factor infertility and at least 3 failed previous IVF attempts may benefit from laparoscopic investigation regarding assisted reproduction outcome

The aim of this study is to assess the value of laparoscopy for couples diagnosed with mild male factor infertility and at least three previous failed In-Vitro Fertilization (IVF) attempts. A total of 169 couples were included in this prospective cohort study. Patients were presented with the option of being subjected to laparoscopic investigation for correction of previously unidentified endometriosis or pelvic adhesions. The outcome measures were Live Birth/Ongoing Pregnancy, clinical pregnancy and positive hCG rate. One-hundred and one of them opted for, whereas 68 opted against laparoscopic investigation. All patients proceeded with a single ICSI cycle. Following laparoscopic investigation, 43 patients were diagnosed with endometriosis, 22 with adhesions, while for 36 patients laparoscopic investigation provided no further diagnosis. No statistically significant differences were observed regarding baseline hormonal levels and other characteristics between the two groups and the three subgroups. When compared to the no-laparoscopy group, women subjected to laparoscopy presented with a higher clinical pregnancy and ongoing pregnancy/live birth rate. Following endometriosis correction, a marginally non-statistically significant trend was observed regarding a decrease in poor-quality blastocysts (p = 0.056). A statistically significant higher clinical pregnancy (p = 0.03) and ongoing pregnancy/live birth rate was observed in the endometriosis group when compared to male factor infertility only (p = 0.04). Laparoscopic identification and correction of undiagnosed endometriosis in couples initially diagnosed with male infertility and at least 3 failed previous IVF attempts, appears to be a promising approach efficiently addressing infertility for these patients while avoiding IVF overuse.

Dehydroepiandrosterone Supplementation Improves the Outcomes of in vitro Fertilization Cycles in Older Patients With Diminished Ovarian Reserve.

Background: Dehydroepiandrosterone (DHEA) supplementation has been reported to have beneficial effects on the in vitro fertilization (IVF) outcomes of patients with poor ovarian response or diminished ovarian reserve. The Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) stratification is a set of newly established criteria for low prognosis patients. The aim of this study was to examine the potential effects of DHEA supplementation on the IVF outcomes of patients who fulfill the POSEIDON group 4 criteria.Methods: This retrospective cohort study investigated 297 cycles that fulfilled the POSEIDON group 4 criteria and underwent IVF treatment using the gonadotropin-releasing hormone antagonist protocol. The study group contained 159 cycles that received DHEA (30 mg three times per day) daily for 12 weeks before their IVF cycles. The control group included 138 cycles that underwent IVF cycles but did not receive DHEA. The baseline characteristics and cycle parameters as well as the IVF outcomes of both groups were compared.Results: In terms of baseline characteristics, more previous IVF attempts and lower AMH levels were found in the study group than in the control group. Regarding IVF outcomes, patients in the study group had significantly higher follicular oocyte index and higher numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality day 3 embryos than those in the control group. Besides, a higher cumulative pregnancy rate and lower cancellation rate were observed in the study group than in the control group although clinical pregnancy rate, live birth rate, and cumulative live birth rate did not differ between the two groups. Whether patients are aged ≤ 40 years or aged > 40, higher numbers of oocytes and embryos were observed in the study group than in the control group. In patients aged > 40, cumulative pregnancy rate was significantly higher in the study group than in the control group.Conclusions: Our data suggest that DHEA supplementation might increase both oocyte and embryo yields, as well as cumulative pregnancy rates, in patients fulfilling the POSEIDON group 4 criteria.

Comparison of pre-treatment with OCPs or estradiol valerate vs. no pre-treatment prior to GnRH antagonist used for IVF cycles: An RCT

Both oral contraceptive pills (OCPs) and estradiol valerate (E2) have been used to schedule a gonadotropin-releasing hormone antagonist in vitro fertilization (IVF) cycles. Since the suppression of follicle-stimulating hormone by OCPs can stay 5-7 days after stopping the pills, it seems that starting the gonadotropin-releasing hormone (GnRH) after 6 days of pre-treatment discontinuation may be important in IVF outcomes. The aim of the present study was to determine the number of mature oocyte and pregnancy rate of three pretreatment methods for fresh embryo transfer cycles. In this randomized controlled trial, two-hundred ten women (18-35 yr and less than 2 previous IVF attempts) undergoing IVF with the GnRH antagonist protocol were randomized to the OCP, E2, and no pretreatment arms. OCP group (n=53) received OCP (ethinyl estradiol30 μg and levonorgestrel150 μg), E2 group (n=63) received 4 mg/day oral E2 (17β-E2) for 10 days from day 20 of the previous cycle and GnRH antagonist stimulation was started 6 days after the interruption of OCP and E2. The control group (n =70) did not receive any pretreatment. No significant difference was observed in the mean number of the mature oocyte, endometrial thickness, and embryo quality. The pregnancy rate in E2 group was higher than the two other groups (42.9% vs 39.6% and 34.3% in OCP and control group, respectively), but the difference was not statistically significant (p=0.59). It seems OCP or E2 pretreatment could not improve the fresh IVF-embryo transfer outcomes.

Live Birth after In Vitro Maturation of Oocytes in a Patient with Repeated Fertilization Failure in IVF: A Case Report

The incidence of fertilization failure has decreased dramatically since the intracytoplasmic sperm injection procedure (ICSI) was successfully introduced into clinical practice. However, even in very successful units with remarkable pregnancy rates, there are couples who face repeated in vitro fertilization (IVF) failure due to low or absence of fertilization. We present a case of a 36-year-old woman with tubal factor of infertility and two previous IVF attempts with short and long agonist protocols and absence of normal fertilization after ICSI. The third cycle performed with in vitro maturation of oocytes (IVM) led to the development of top quality embryos. Two transferred embryos ensued in a singleton pregnancy and term delivery of a healthy girl.

Frozen embryo transfer: the present practice and beyond

With the success of oocyte donation in vitro fertilization (IVF) in postmenopausal women, the importance of endometrial preparation became obvious. This appears also very crucial for achieving pregnancy after frozen embryo transfer (FET) after failed fresh IVF cycles and FET in subsequent natural cycles. Although there are different methods of preparing endometrium, in this study, another method of preparing the implantation bed using letrozole was scrutinized for its usefulness. Two hundred and seventy patients between 28 and 40 years of age undergoing IVF due to bilateral tubal blocks were chosen for FET. They had a previous unsuccessful single IVF attempt or had postponed embryo transfer due to the threat of ovarian hyperstimulation syndrome or poor endometrial development. Informed consents were obtained from the participants. One hundred patients had endometrial preparation by gonadotrophin-releasing hormone agonist down-regulation and with hormone replacement therapy, 55 had natural cycle FET, and the remaining 115 patients had letrozole-induced ovulation induction (OI) for endometrial preparation. The clinical and biochemical pregnancy rate or live birth rate was higher in the letrozole OI group than in the other two groups. OI by letrozole and subsequent endometrial preparation as a result of it may be utilized for FET, and this will be cheap and easy to administer, giving better success rates in FET cycles.

The impact of fetal gender on prematurity in dichorionic twin gestations after in vitro fertilization

BackgroundImpact of fetal gender on prematurity has been primarily investigated in singleton pregnancies. In an attempt to understand better how fetal gender may affect gestational length in twin gestations after in vitro fertilization, same-sex twins and opposite twins were compared for pregnancy duration.MethodsThis study evaluated 113 women at ages 20 to 39 years with consecutive dichorionic-diamniotic twin gestations after assisted reproduction. All pregnancies were results of fresh in vitro fertilization (IVF) cycles with use of autologous oocytes and sperm and were delivered at up to 37 weeks of gestation at a University-based high-risk, maternal-fetal medicine unit.ResultsBoth groups did not differ in baseline characteristics, such as maternal ages, indications for fertility treatments, number of previous IVF attempts, body mass index and parity. Opposite sex- twins, however, presented with significantly shorter gestational age at birth (32.9 +/- 3.4 weeks) than same-sex twins (34.3 +/- 2.5 weeks), (p < 0.05). Younger maternal age was also associated with shorter pregnancy duration (p < 0.05).ConclusionsFetal gender mix serves as risk factor for more significant prematurity in dichorionic-diamniotic twins after assisted reproduction with opposite sex twins at higher risk than same sex-twins.

Extensive Excision of Deep Infiltrative Endometriosis before In Vitro Fertilization Significantly Improves Pregnancy Rates

Study Objective We sought to compare the outcomes of in vitro fertilization (IVF) treatments in women with infertility-associated deep infiltrative endometriosis (DIE) who underwent extensive laparoscopic excision of endometriosis before IVF with those who underwent IVF only. Design Prospective cohort study. Setting Infertility clinic and private hospital in São Paulo, Brazil. Patients A total of 179 infertile patients younger than 38 years had symptoms and/or signs of endometriosis and sonographic images suggestive of DIE. Interventions After thorough counseling, 179 women were invited to participate in a prospective cohort study with 2 treatment options: IVF without undergoing laparoscopic surgery (group A, n = 105) and extensive laparoscopic excision of DIE before IVF (group B, n = 64). Ten women were lost to follow-up. The IVF outcomes were compared between the 2 groups. Measurements and Main Results In group B, patients had 5 ± 2 (mean ± SD) DIE lesions excised during laparoscopy. Patient characteristics in groups A and B, respectively, were: age (32 ± 3 vs 32 ± 3 years, p = .94), infertility duration (29 ± 20 vs 27 ± 17 months, p = .45), day-3 serum follicle-stimulating hormone levels (5.6 ± 2.5 vs 5.9 ± 2.5 IU/L, p = .50), and previous IVF attempts (1 ± 1 vs 2 ± 1, p = .01). The IVF outcomes differed between groups A and B, respectively, with regard to total dose of recombinant follicle-stimulating hormone required to accomplish ovulation induction (2380 ± 911 vs 2542 ± 1012 IU, p = .01), number of oocytes retrieved (10 ± 5 vs 9 ± 5, p = .04), and pregnancy rates (24% vs 41%, p = .004), but not number of embryos transferred (3 ± 1 vs 3 ± 1, p = 1). The odds ratio of achieving a pregnancy were 2.45 times greater in group B than in group A. Conclusion Extensive laparoscopic excision of DIE significantly improved IVF pregnancy rates of women with infertility-associated DIE.

503. SUCCESSFUL IN VITRO FERTILIZATION (IVF) AFTER PRIOR FAILED IVF UTILIZING A PROPRIETARY BLEND OF SUPPLEMENTS

Background: To date, little is known about the effect of supplements on the outcome of in vitro fertilization (IVF). The data on this matter is limited to measuring the overall pregnancy rate on a population of women who took a specific supplement, and not on IVF patients. Objectives: To demonstrate the positive role of an investigated supplement in the outcome of patients undergoing IVF. Method: 18 women undergoing IVF treatment were placed on a proprietary combination of vitamins and antioxidants designed to encourage blood flow and improve egg quality. The women were selected for this protocol mostly due to prior poor egg quality and/or large amount of embryo fragmentation .The women took supplementation twice daily for 4–12 weeks prior to transfer. The charts of the patients who used the supplements were used to obtain data. Previous failed IVF was defined as negative pregnancy. Successful IVF outcome was determined by positive chemical pregnancy and clinical pregnancy after one attempt. Range and mean was calculated for patient's age and number of failed previous IVF attempts. The previous IVF attempts were performed in different centers without using this supplement in all patients. Results: Eighteen patients used the supplement before and during their IVF cycles. Patient's age ranged from 28 to 44 with mean of 36.4 years. They had on average, 2 prior failed IVF attempts. Seventeen of 18 patients had successful IVF outcome. The failed patient required frozen testicular extraction of sperm (TESE), prior to IVF. Summary: Seventeen of 18 patients who used our supplements had successful IVF. These patients failed an average of 2 previous IVF attempts without using our supplements. Conclusion: Usage of our supplements is associated with improved rates of success in patients undergoing IVF with a history of prior failed IVF attempts. Larger studies need to be conducted.

Factors Influencing Adverse Perinatal Outcomes in Pregnancies Achieved Through Use of Assisted Reproductive Technology (ART)

Factors Influencing Adverse Perinatal Outcomes in Pregnancies Achieved Through Use of Assisted Reproductive Technology (ART)

Comparison between intracytoplasmic sperm injection and in-vitro fertilization (IVF) with high insemination concentration after total fertilization failure in a previous IVF attempt

The aim of this prospective study was to evaluate whether couples with total fertilization failure in a previous in-vitro fertilization (IVF) attempt should be offered an additional IVF treatment with elevated insemination concentration or should be treated with intracytoplasmic sperm injection (ICSI). In 23 cycles 228 sibling metaphase II (MII) oocytes were randomly divided: 143 and 85 oocytes were utilized for ICSI and IVF respectively. Of the 143 injected (ICSI) oocytes, 90 (62.9%) were normally fertilized (two pronuclei), whereas 21 (14.7%) oocytes were damaged by the ICSI procedure. Of the fertilized oocytes 72 (80%) developed into transferable embryos. No fertilization at all was observed in the 85 sibling MII oocytes which were inseminated (P < 0.001). In all 23 cycles at least one embryo, obtained by ICSI, could be replaced. Eight pregnancies were achieved of which six resulted in the delivery of nine healthy children. In conclusion, for couples with no or almost no fertilization of oocytes in previous IVF attempts, ICSI appeared to be far superior to an additional IVF attempt with further elevated insemination concentrations.

The effect of human menopausal gonadotrophin and highly purified, urine-derived follicle stimulating hormone on the outcome of in-vitro fertilization in down-regulated normogonadotrophic women

It has been suggested that the luteinizing hormone (LH) activity of human menopausal gonadotrophin (HMG) preparations used for ovarian stimulation in in-vitro fertilization (IVF) may have adverse effects on reproductive outcome. In the present prospective, randomized trial of 218 infertile couples this notion was investigated. A total of 114 women were treated with Pergonal (HMG group) and 104 with Fertinorm HP (HP-FSH group). The two groups were comparable with regard to duration of infertility, cause of infertility, age and number of previous IVF attempts and all had normal basal gonadotrophin concentrations before treatment was started. A standard hormonal treatment consisting of pituitary down-regulation with gonadotrophin-releasing hormone analogue (GnRHa) for 14 days starting on cycle day 21, followed by either HMG or highly purified follicle stimulating hormone (HP-FSH), three ampoules (225 IU) per day for 7 days, was used in all cases. The daily hormone dose was thereafter individualized according to the ovarian response. A maximum of two pre-embryos were transferred after 3 days of culture. Luteal support with progesterone (300 mg per day intravaginally) was used in all cases. Serum concentrations of oestradiol, FSH and LH were measured on days 1 and 8 of stimulation and on the day of oocyte retrieval. The mean number of days of stimulation, mean number of ampoules of HMG or HP-FSH used, mean total motile sperm count on the day of oocyte retrieval and mean numbers of oocytes retrieved (13.4 versus 13.7) or pre-embryos transferred (1.8 versus 1.8) were similar for both groups. Significantly (P < 0.05) more cycles in the HP-FSH group (17 = 16%) were cancelled due to complete failure of fertilization than in the HMG group (7 = 6%). The mean fertilization rate was significantly (P < 0.05) higher in the HMG group (56%) than in the HP-FSH group (50%), and significantly more transferable pre-embryos were obtained in the HMG than in the HP-FSH group (mean: 4.0 versus 3.2; P < 0.01). Serum hormone concentrations were similar to the two groups on stimulation day 1, but differed significantly with regard to FSH, LH and oestradiol on stimulation day 8. The clinical outcome was similar in the two groups, with an ongoing pregnancy rate (> 12 weeks of gestation) per started cycle of 33% in the HMG group and 29% in the HP-FSH group. The clinical abortion rates were similar (10 and 14%), and the implantation rate was 30% in each group. In conclusion, no detrimental effect of the LH activity of HMG on the clinical outcome of IVF in GnRHa down-regulated normogonadotrophic women was found. To the contrary, some beneficial effects of HMG on fertilization rates and pre-embryo development as compared with HP-FSH were demonstrated. These effects, as well as the differences in serum hormone concentrations during ovarian stimulation, may be caused by differences in LH content and/or in the composition of FSH isoforms of the HMG and HP-FSH preparations.

Partial zona dissection enhances the fertilization rate in cases of sperm defect only when total failure has occurred in previous in-vitro fertilization attempts

The value of partial zona dissection (PZD) was assessed in a randomized protocol of in-vitro fertilization (IVF) including 30 couples (44 cycles) with at least two sperm defects. Couples were divided into three groups according to previous IVF status, i.e. group I: total failure of previous IVF; group II: marginal success of previous IVF, and group III: no previous IVF. Both PZD and untreated oocytes were inseminated using the swim-across method. Although PZD did not enhance the overall proportion of fertilized eggs resulting in diploid cleaving embryos per retrieved oocyte (14.7 versus 17.1%), this rate was higher with PZD than with IVF when previous IVF attempts had failed (group I: 16.1 versus 4.5%, P < 0.01). The rate was similar for PZD and IVF in group II, and lower for PZD than IVF in group III (15.1 versus 30.8%, P < 0.01). The higher polyspermy rate associated with PZD in groups in which classical IVF worked, could partially explain these results. The role of a possible deleterious effect of PZD on the oocytes is discussed. Out of the 44 cycles, 20 reached the embryo transfer stage and four pregnancies were obtained. In our opinion PZD should be carried out in cases of sperm defects only when previous IVF attempts have failed.