Cumulative live birth rates following insemination with donor spermatozoa in single women, same-sex couples and heterosexual patients.

RESEARCH QUESTION: What is the cumulative live birth rate (LBR) following donor intrauterine insemination (IUI-D) treatment in a large, retrospective, single-centre cohort of single women, same-sex couples and heterosexual patients? DESIGN: Outcomes from 8922 treatments performed in 3333 consecutive women (45% single, 43% from same-sex and 12% from heterosexual couples) were analysed in a 13-year retrospective study from a private, HFEA-regulated UK centre between January 2004 and December 2016. RESULTS: A total of 795 live births resulted in an overall delivery rate of 8.9% per cycle, including 24 (3%) twins. Age-specific crude and expected cumulative LBR calculated in four age groups (<35, 35-37, 38-39 and 40-42 years) were 29, 23, 21, 12% and 66, 49, 54, 28%, respectively. A plateau was reached after six cycles, beyond which there were few additional live births. There was no significant difference in cumulative LBR between single women and same-sex couples. In a multivariate analysis, female age (adjusted odds ratio [aOR] 0.92; 95% confidence interval [CI] 0.90-0.93; P < 0.0001), previous live birth following IUI-D (aOR 2.15; 95% CI 1.69-2.73; P < 0.0001) and mild stimulation (aOR 1.27; 95% CI 1.09-1.48; P = 0.02) had a significant effect on outcome, but relationship status or cycle rank did not. CONCLUSIONS: These results indicate there is little benefit performing more than six cycles of IUI-D in all women up to 40 years old, including those from same-sex relationships, while only three attempts seem reasonable in those aged 40-42 years. These results do not reflect current clinical guidelines in the UK. The authors found that consecutive IUI cycles, especially with mild stimulation, were an efficient treatment in all indications.

Endogenous progesterone levels could predict reproductive outcome in frozen embryo replacement cycles supplemented with synthetic progestogens: A retrospective cohort study.

PURPOSE: A retrospective, cohort study was conducted between 2009 and 2017 in a private infertility center to determine the predictive value of endogenous estrogen (E2) and progesterone (P4) levels in hormone-replacement frozen embryo replacement (FER) treatment cycles. METHODS: A total of 120 consecutive, infertile patients who became pregnant after FER cycles were analyzed (age: 37.4 ± 4.4 years). Electively vitrified blastocysts were created during natural cycle IVF or mild ovarian stimulation treatments and subsequently transferred through delayed vitrified-thawed blastocyst transfer cycles supplemented with estrogens and a combination of synthetic progestogens. Serum E2 and progesterone P4 levels were intensively monitored every five days (from the day after embryo transfer until 9w1d of pregnancy) and compared among patients with a subsequent live birth (n = 76) or first-trimester pregnancy loss (n = 44). RESULTS: Endogenous placental activity started as early as 5-6th pregnancy week differing significantly according to pregnancy outcome. For P4, the exponential rise from 6w2d onwards allowed distinguishing between failing and successful conceptions. For P4, lower quartiles of the live birth group did not intersect with upper quartiles of the miscarriage group. CONCLUSIONS: Innovative FER protocols incorporating synthetic progestogens allow the correct measurement of endogenous placental activity and could help to monitor early first-trimester ART pregnancies.

Predicting live birth by combining cleavage and blastocyst-stage time-lapse variables using a hierarchical and a data mining-based statistical model.

Prolonged embryo culture is increasingly used as a way of improving pregnancy rates, especially in the context of single embryo transfer. So far, only a handful of studies examined the relation between implantation potential and time-lapse parameters extracted from later stages (morula and blastocyst) of embryo development. For this retrospective study all 285 single vitrified-thawed blastocyst transfers (SVBT) from all consecutive unselected patients whose fertilized oocytes were submitted to time-lapse monitoring (TLM) from a two-year cohort were analysed. Two different statistical models were created; a hierarchical one including the two strongest live birth (LB) predictors (t2 and texpB2) and a more complex model based on principal component analysis (PCA) and logistic regression methods. The first, four-category, hierarchical model effectively distinguished between blastocysts of increasing LB rates (8, 30, 40, 53%). For the second data-mining model quartiles of the created Sc parameter had increasing LB rates (12, 19, 40, 49%). AUC values were comparable for both models (0.723, 95CI%:0.66-0.79 versus 0.717, 95CI%:0.65-0.78). The combination of cleavage- and blastocyst-stage variables through hierarchical or data mining-based algorithms was used successfully to predict live birth. However, due to the lack of internal / external validation the predictive capacities of this model could differ largely in different datasets.

Time-lapse variables and embryo gender: a retrospective analysis of 81 live births obtained following minimal stimulation and single embryo transfer.

PURPOSE: The purpose of this study was to determine which morphokinetic variables are related to embryo gender in a cohort of consecutive live births obtained through single blastocyst transfer following mild ovarian stimulation. METHODS: Eighty-one live births (49 % of them females) from successfully treated, consecutive infertile patients (maternal age 36.9 ± 3.8 years, range 28-46) who underwent minimal ovarian stimulation, prolonged embryo culture in a time-lapse monitoring (TLM) incubator and elective single blastocyst transfers during 2012-2014. Early (PNf, t2-t9, cc2a, b, s2, s3) and late (tM, tSB, tfullB, texpB1, and texpB2) morphokinetic variables were scored according to published consensus criteria and were normalized to the time of pronuclear fading. For each variable, the ranges with the highest proportion of female embryos (optimal range) were determined by detailed examination of histograms. RESULTS: Female embryo gender was associated both with late cleavage (t8), morula (tM), and blastocyst stage morphokinetic variables. The strongest associations (adjusted ORs, 7.0-7.8) were found for late, expanded stage blastocyst parameters; tfullB, texpB1, and texpB2. The proportion of female embryos was 69-71 and 25-26 % inside and outside of the optimal ranges, respectively. This allowed to predict 74-78 % of them, increasing their proportion by 57 % compared to the average. CONCLUSIONS: Although the sample size of our cohort was limited, our findings suggest that several expanded blastocyst stage morphokinetic parameters are associated with female embryo gender. If confirmed on a larger sample these could be potentially used to increase the proportion of female embryos among non-invasively selected blastocysts following single embryo transfer.

Blastocyst collapse is not an independent predictor of reduced live birth: a time-lapse study.

OBJECTIVE: To ascertain the rate of blastocyst collapse observed by time-lapse monitoring in a retrospective cohort of unselected infertile patients undergoing single blastocyst transfer and to determine its association with live birth. DESIGN: Blastocyst collapse and morphokinetic variables were scored according to previously published criteria. The association between blastocyst collapse and live birth was evaluated by a multivariate logistic regression analysis including morphokinetic variables and other confounders. SETTING: Private infertility clinic. PATIENT(S): Patients who underwent 277 consecutive single blastocyst transfers (mean age, 38.4 ± 3.9 years; range, 28-47 years) after minimal ovarian stimulation. INTERVENTION(S): Minimal ovarian stimulation, prolonged embryo culture in time-lapse monitoring incubator, elective vitrification with subsequent vitrified-warmed single blastocyst transfer. MAIN OUTCOME MEASURE(S): Live birth rate per single blastocyst transfer in different blastocyst collapse groups (no, single, multiple collapses). RESULT(S): No, single, or multiple blastocyst collapses occurred in 54% (150/277), 22% (61/277), and 24% (66/277) of the cohort, respectively. In the multiple collapse group on average 2.9 contractions were seen (range, 2-9 contractions). Live birth rate decreased progressively between blastocyst collapse groups (36%, 31%, 14%); significantly lower if multiple collapses occurred. In a multivariate analysis, however, blastocyst collapse was not found to be a significant predictor and was confounded by stronger predictors such as morphokinetic variables t2, texpB2, and female age. CONCLUSION(S): Blastocyst collapse pattern should not be evaluated alone without taking into account morphokinetic variables that are stronger predictors of reproductive outcome.

Minimal stimulation IVF vs conventional IVF: a randomized controlled trial.

BACKGROUND: Minimal stimulation in vitro fertilization (mini-in vitro fertilization) is an alternative in vitro fertilization treatment protocol that may reduce ovarian hyperstimulation syndrome, multiple pregnancy rates, and cost while retaining high live birth rates. OBJECTIVE: We performed a randomized noninferiority controlled trial with a prespecified border of 10% that compared 1 cycle of mini-in vitro fertilization with single embryo transfer with 1 cycle of conventional in vitro fertilization with double embryo transfer. STUDY DESIGN: Five hundred sixty-four infertile women (<39 years old) who were undergoing their first in vitro fertilization cycle were allocated randomly to either mini-in vitro fertilization or conventional in vitro fertilization. The primary outcome was cumulative live birth rate per woman over a 6-month period. Secondary outcomes included ovarian hyperstimulation syndrome, multiple pregnancy rates, and gonadotropin use. The primary outcome was cumulative live birth per randomized woman within a time horizon of 6 months. RESULTS: Five hundred sixty-four couples were assigned randomly between February 2009 and August 2013 with 285 couples allocated to mini-in vitro fertilization and 279 couples allocated to conventional in vitro fertilization. The cumulative live birth rate was 49% (140/285) for mini-in vitro fertilization and 63% (176/279) for conventional in vitro fertilization (relative risk, 0.76; 95% confidence interval, 0.64-0.89). There were no cases of ovarian hyperstimulation syndrome after mini-in vitro fertilization compared with 16 moderate/severe ovarian hyperstimulation syndrome cases (5.7%) after conventional in vitro fertilization. The multiple pregnancy rates were 6.4% in mini-in vitro fertilization compared with 32% in conventional in vitro fertilization (relative risk, 0.25; 95% confidence interval, 0.14-0.46). Gonadotropin consumption was significantly lower with mini-in vitro fertilization compared with conventional in vitro fertilization (459 ± 131 vs 2079 ± 389 IU; P < .0001). CONCLUSION: Compared with conventional in vitro fertilization with double embryo transfer, mini-in vitro fertilization with single embryo transfer lowers live birth rates, completely eliminates ovarian hyperstimulation syndrome, reduces multiple pregnancy rates, and reduces gonadotropin consumption.

Influence of different oocyte insemination techniques on early and late morphokinetic parameters: retrospective analysis of 500 time-lapse monitored blastocysts.

OBJECTIVE: To determine how standard IVF vs. intracytoplasmic sperm injection (ICSI) fertilization influences early and late morphokinetic parameters during prolonged embryo culture. DESIGN: Five-hundred expanded blastocysts that were monitored in a time-lapse monitoring incubator were analysed retrospectively. Early (pronuclear fading [PNf], t2-t9) and late (start of blastulation, expanded blastocyst) morphokinetic variables were scored according to published consensus criteria. SETTING: Private infertility clinic. PATIENT(S): A total of 209 consecutive infertile patients (mean ± SD age, 38.4 ± 4 years; range, 28-47 years) undergoing 238 natural IVF/minimal ovarian stimulation cycles during 2012-2014. INTERVENTION(S): Minimal ovarian stimulation, oocyte retrieval, fertilization with standard IVF or ICSI, prolonged embryo culture in a time-lapse monitoring incubator. MAIN OUTCOME MEASURE(S): Differences in morphokinetic parameters according to insemination techniques. RESULT(S): In total, 29% and 71% of the whole cohort was fertilized with standard IVF and ICSI, respectively. During early cleavage stages (PNf to t4) there was a statistically significant delay (+1.5 to +1.1 hours) among IVF-fertilized embryos. By contrast, at the expanded blastocyst stage IVF-fertilized embryos showed faster development (-3.3 to -4.1 hours). After normalizing to the time point of PNf, differences in cleavage-stage parameters disappeared, but those at all blastocyst stages increased even further in favor of IVF-fertilized embryos (-3.2 to -5.7 hours). CONCLUSION(S): The observed 1.5-hour time difference between standard IVF- and ICSI-fertilized embryos is an artificial phenomenon. At the blastocyst stages, however, genuine timing differences arise between IVF- and ICSI-fertilized embryos, possibly related to their different quality. Normalization to a common time point permits the joint analysis of IVF- and ICSI-fertilized embryos, thus increasing the size of studied cohorts.

Time-lapse monitoring of zona pellucida-free embryos obtained through in vitro fertilization: a retrospective case series.

OBJECTIVE: To report time-lapse monitoring of human oocytes in which the damaged zona pellucida was removed, producing zona-free (ZF) oocytes that were cultured until the blastocyst stage in time-lapse incubators. DESIGN: Retrospective case series. SETTING: Private infertility clinic. PATIENT(S): Infertile patients (n = 32) undergoing minimal ovarian stimulation or natural cycle IVF treatment between October 2012 and June 2014. INTERVENTION(S): Intracytoplasmic sperm injection (ICSI) fertilization of ZF oocytes, prolonged embryo culture in time-lapse incubators, elective vitrification, and subsequent single vitrified-thawed blastocyst transfer (SVBT). MAIN OUTCOME MEASURE(S): Rate of fertilization, cleavage and blastocyst development, live-birth rate per SVBT cycle. RESULT(S): In spite of advanced maternal age (39 ± 4.2; range, 30-46 years), good fertilization (94%), cleavage (94%), and blastocyst development rates (38%) were reached after fertilization and culturing of ZF oocytes/embryos. All thawed ZF blastocysts survived, and up to this date seven SVBT transfers were performed, yielding three (43%) term live births with healthy newborns. CONCLUSION(S): Time-lapse imagery gives a unique insight into the dynamics of embryo development in ZF embryos. Moreover, our case series demonstrate that an oocyte with a damaged zona pellucida that has been removed could be successfully fertilized with ICSI, cultured until blastocyst stage in a time-lapse incubator and vitrified electively for subsequent use.

Developmental potential of zona pellucida-free oocytes obtained following mild in vitro fertilization.

OBJECTIVE: To determine the developmental potential of oocytes in which the zona pellucida was damaged and subsequently removed, producing "zona-free" (ZF) oocytes that were cultured until the blastocyst stage. DESIGN: ZF eggs from cycles with more than one oocytes retrieved (n = 97) were compared with zona-intact (ZI) oocytes originating from the same patient. SETTING: Private infertility clinic. PATIENT(S): Infertile patients (n = 135) undergoing minimal ovarian stimulation or natural-cycle in vitro fertilization treatment during 2010-2012. INTERVENTION(S): ZF oocytes undergoing intracytoplasmic sperm injection (ICSI) fertilization, blastocyst culture, elective vitrification, and subsequent single vitrified-thawed blastocyst transfer (SVBT). MAIN OUTCOME MEASURE(S): Rate of fertilization, cleavage, and blastocyst development. Live birth rate and neonatal outcome in subsequent SVBT cycles. RESULT(S): There were no significant differences in fertilization (77% vs. 77%), cleavage (75% vs. 75%), or blastocyst development rates (39% vs. 32%) between the internally controlled ZF and ZI groups, respectively. Survival after thawing (90% vs. 100%) and live birth rates (37% vs. 36%) per thawed blastocyst were also similar. Newborns originating from all ZF and ZI oocytes had a similar gestational age at delivery (38.3 ± 3.7 wk vs. 39.5 ± 1.5 wk) and birth weight (3,115 ± 946 g vs. 3,010 ± 441 g). CONCLUSION(S): Our retrospective comparative study suggests that ZF eggs could be as successfully fertilized and cultured until the blastocyst stage as ZI control eggs without adversely affecting subsequent pregnancy rates and basic neonatal outcome.

Cumulative success rates following mild IVF in unselected infertile patients: a 3-year, single-centre cohort study.

A 3-year, retrospective, single-centre cohort study was conducted in a private infertility centre to determine cumulative live birth rates (LBR) per scheduled oocyte retrieval following minimal ovarian stimulation/natural-cycle IVF in unselected infertile patients. A total of 727 consecutive infertile patients were analysed who underwent 2876 (median 4) cycles with scheduled oocyte retrieval from November 2008 to December 2011. Natural-cycle IVF or clomiphene-based minimal ovarian stimulation was coupled with single-embryo transfer and increased use of delayed vitrified-warmed blastocyst transfer. Main outcome measures were crude and expected age-specific cumulative LBR per scheduled oocyte retrieval. Crude cumulative LBR were 65%, 60%, 39%, 15% and 5% in patients aged 26-34, 35-37, 38-40, 41-42 and 43-44 years, respectively. No live births occurred in patients aged ⩾ 45 years. Dropout rates per cycle were 13-25%. Success rates gradually reached a plateau, with few additional live births after six cycles. Most of the expected success rate was reached within 6 months with almost maximal rates within 15 months of the first oocyte retrieval. Acceptable cumulative LBR are reached with an exclusive minimal ovarian stimulation/single-embryo transfer policy especially in patients aged <38 years but also in intermediate aged patients (38-40 years).

Oocyte retrieval timing based on spontaneous luteinizing hormone surge during natural cycle in vitro fertilization treatment.

OBJECTIVE: To determine the efficiency of oocyte retrieval (OR) timing based on the occurrence of spontaneous LH surge during natural cycle IVF (ncIVF) treatment. DESIGN: Retrospective cohort study. The cohort was divided into five subgroups according to the presumed stage of spontaneous LH surge on scheduling day (1A: before onset; 1B: surge start; 2: ascending slope; 3: peak; and 4: descending slope). SETTING: Private infertility clinic. PATIENT(S): Three hundred sixty-five infertile patients who underwent 1,138 ncIVF treatment cycles during 2008-2011. INTERVENTION(S): Drug-free ncIVF treatment. MAIN OUTCOME MEASURE(S): Rate of successfully retrieved, fertilized oocytes, cleaved embryos, and live births per scheduled oocyte retrieval. RESULT(S): In 61% of the cycles OR was scheduled before or just at the start of the LH surge (groups 1A-1B), whereas in the remaining cases it was scheduled after the surge had already started (groups 2-4). The proportion of cycles with successfully recovered (range, 71%-86%), inseminated (range, 61%-78%), fertilized oocytes (range, 47%-68%), cleaved embryos (range, 45%-66%), and live births (range, 4.1%-9.2%) was not significantly different among subgroups. CONCLUSION(S): In ncIVF treatment OR timing based on the occurrence of spontaneous LH surge is feasible, yielding acceptable oocyte recovery, fertilization, and embryo cleavage rates. This strategy combined with a rapid and low-risk OR procedure permits the management of a large ncIVF program on a 7-days-per-week basis within working hours.

Minimal ovarian stimulation combined with elective single embryo transfer policy: age-specific results of a large, single-centre, Japanese cohort.

BACKGROUND: The two main complications associated with the use of assisted reproduction techniques, ovarian hyperstimulation syndrome and multiple pregnancies, could be eliminated by milder ovarian stimulation protocols and the increased use of a single embryo transfer (SET) policy. A retrospective, cohort study was performed in private infertility centre to evaluate the embryological and clinical results of a large exclusively SET program according to patient age (lower or equal 29, 30-34, 35-39, 40-44 and equal or higher 45 years). MATERIALS: A total of 7,244 infertile patients have undergone 20,244 cycles with a clomiphene-based minimal stimulation or natural cycle IVF protocol during 2008. Following oocyte retrieval, fertilization and embryo culture a total of 10,401 fresh or frozen single embryo transfer procedures were performed involving cleavage-stage embryos or blastocysts. RESULTS: Successful oocyte retrieval rate (78.0 %) showed no age-dependent decrease until 45 years. Fertilization (80.3 %) and cleavage (91.1 %) rates were not significantly different between age groups. Blastocyst formation (70.1 % to 22.8 %) and overall live birth rates (35.9 % to 2 %) showed an age-dependent decrease. Frozen-thawed blastocyst transfer cycles gave the highest chance of live birth per embryo transfer (41.3 % to 6.1 %). CONCLUSIONS: High fertilization and cleavage rates were obtained regardless of age whereas blastocyst formation and live birth rates showed an age-dependent decrease. An elective single embryo transfer program based on a minimal ovarian stimulation protocol yields acceptable live birth rates per embryo transfer in infertile patients up until their mid-forties. However in very advanced age patients (equal or higher 45 years old) success rates fall below 1 %.

Short-term, low-dose, non-steroidal anti-inflammatory drug application diminishes premature ovulation in natural-cycle IVF.

A retrospective cohort study was conducted in a private infertility centre to evaluate the use of non-steroidal antiinflammatory drugs (NSAID) in natural-cycle IVF (nIVF) treatment. A total of 1865 first-rank nIVF cycles performed during 2009­2010 were evaluated. Low-dose, post-trigger NSAID was administered in a non-randomized way in cycles at higher ovulation risk where an imminent LH surge was detected on triggering day. Main outcome measures were premature ovulation rate, embryo transfer rate per scheduled cycle and clinical pregnancy and live birth rates per embryo transfer. NSAID use was associated with a significantly lower risk of premature ovulation (3.6% versus 6.8%, adjusted OR 0.24, 95% CI 0.15­0.39, P < 0.0001) and higher embryo transfer rate (46.8% versus 39.5%, adjusted OR 1.38, 95% CI 1.06­1.61, P = 0.012) per scheduled cycle. Clinical pregnancy (39.1% versus 35.9%) and live birth rates per embryo transfer (31.3% versus 31.4%) were comparable. In this retrospective series, short-term low-dose NSAID application positively influenced nIVF cycles by diminishing the rate of unwanted premature ovulations and increasing the proportion of cycles reaching embryo transfer.

Neonatal outcome and birth defects in 6623 singletons born following minimal ovarian stimulation and vitrified versus fresh single embryo transfer.

OBJECTIVE: To compare neonatal outcome between children born after vitrified versus fresh single-embryo transfer (SET). STUDY DESIGN: Retrospective, single-centre cohort study of 6623 delivered singletons following 29,944 single-embryo transfers. Patients underwent minimal ovarian stimulation/natural cycle IVF followed by SET of fresh or vitrified-warmed (using Cryotop, Kitazato) cleavage-stage embryos or blastocysts. Outcome measures were gestational age at delivery, birth weight, birth length, low birth weight (LBW), small for gestational age (SGA) and large for gestational age (LGA) infants, perinatal mortality and minor/major birth defects (evaluated by parent questionnaire). RESULTS: Gestational age (38.6 ± 2 versus 38.7 ± 1.9 weeks) and preterm delivery rate (6.9% versus 6.9%, aOR: 0.96 95%CI: 0.76-1.22) in singletons born after the transfer of vitrified embryos were comparable to those born after the transfer of fresh embryos. Children born after the transfer of vitrified embryos had a higher birth weight (3028 ± 465 versus 2943 ± 470 g, p<0.0001) and lower LBW (8.5% versus 11.9%, aOR: 0.65 95%CI: 0.53-0.79) and SGA (3.6% versus 7.6% aOR: 0.43 95%CI: 0.33-0.56) rates. Total birth defect rates (including minor anomalies) (2.4% versus 1.9%, aOR: 1.41 95%CI: 0.96-2.10) and perinatal mortality rates (0.6% versus 0.5%, aOR: 1.02 95%CI: 0.21-4.85) were comparable between the vitrified and fresh groups. CONCLUSIONS: Vitrification of embryos/blastocysts did not increase the incidence of adverse neonatal outcomes or birth defects following single embryo transfer.

Transvaginal versus transabdominal ultrasound guidance for embryo transfer in donor oocyte recipients: a randomized clinical trial.

OBJECTIVE: To compare pregnancy and implantation rates with transvaginal (TV) versus transabdominal (TA) ultrasound-guided embryo transfer (ET). DESIGN: Randomized, clinical trial registered at clinicaltrials.gov (NCT 01137461). SETTING: Private, infertility clinic. PATIENT(S): Three-hundred thirty randomized recipients of donor oocytes. INTERVENTION(S): Embryo transfer using TV (with empty bladder, using the Kitazato ET Long catheter) versus TA ultrasound guidance (with full bladder, using the echogenic Sure View Wallace catheter). MAIN OUTCOME MEASURE(S): Overall pregnancy, clinical pregnancy, implantation, and ongoing pregnancy rates. Duration and difficulty of ET. Patient-reported uterine cramping and discomfort, as evaluated by questionnaire. RESULT(S): No statistically significant differences were observed in clinical pregnancy 50.9% versus 49.4% (95% confidence interval of the difference: -9.2 to +12.2%), implantation 34.5% versus 31.4% (95% CI of the difference: -4 to +10.3%) between the TV and TA ultrasound-guided groups. Transfer difficulty (6% versus 4.2%) and uterine cramping (27.2% versus 18.3%) were not statistically significantly different between treatment groups. Total duration (154±119 versus 85±76 seconds) was statistically significantly higher in the TV ultrasound group. Light to moderate-severe discomfort related to bladder distension was reported by 63% of the patients in the TA ultrasound group. CONCLUSION(S): Transvaginal ultrasound-guided ET yielded similar success rates compared with the TA ultrasound-guided procedure without requiring the assistance of a sonographer. It was associated with increased patient comfort due to the absence of bladder distension.

Blastocyst culture is associated with an elevated incidence of monozygotic twinning after single embryo transfer.

In a 7-year (2002-2008) retrospective study of a large IVF program based on minimal ovarian stimulation and single ET (47,841 single ETs), monozygotic twinning occurred in 1.01% of 14,956 clinical pregnancies. Blastocyst culture was associated with a significantly increased monozygotic twinning risk (adjusted odds ratio, 2.04; 95% confidence interval, 1.29-4.48), whereas embryo freezing, type of stimulation protocol used, intracytoplasmic sperm injection fertilization, or zona removal did not influence its incidence.

Gonadotropin-releasing hormone agonists versus antagonists for controlled ovarian hyperstimulation in oocyte donors: a systematic review and meta-analysis.

OBJECTIVE: To compare GnRH agonists and antagonists in oocyte-donation IVF treatment cycles by a systematic review and meta-analysis of trials. DESIGN: Systematic review and meta-analysis of randomized clinical trials (RCT). Systematic literature searches were conducted, and all randomized trials that compared GnRH agonists with antagonists in oocyte-donation IVF treatment cycles were included. Study selection, quality appraisal, and data extractions were performed independently and in duplicate. SETTING: Tertiary fertility center. PATIENT(S): A total of 1,024 oocyte donors treated in eight RCTs. INTERVENTION(S): Comparison of GnRH agonists versus antagonists in oocyte-donation IVF treatment. MAIN OUTCOME MEASURE(S): Ongoing pregnancy, oocytes retrieved, duration of stimulation, gonadotropin consumption, and ovarian hyperstimulation syndrome incidence (OHSS) per randomized oocyte donor. RESULT(S): Meta-analysis of these studies showed no significant difference in ongoing pregnancy rate between the GnRH agonists and antagonists (risk ratio [RR] 1.15, 95% confidence interval [CI] 0.97 to 1.36). The duration of stimulation was significantly lower with the GnRH antagonist protocol (weighed mean difference [WMD] -0.90 days, 95% CI -1.61 to -0.20). No significant differences were observed in the number of oocytes retrieved (WMD -0.60, 95% CI -2.26 to +1.07), gonadotropin consumption (WMD -264 IU, 95% CI -682 to +154), or OHSS incidence (RR 0.62, 95% CI 0.18 to 2.15). CONCLUSION(S): No significant differences were observed in ongoing pregnancy rate or the number of retrieved oocytes after donor stimulation with GnRH agonist or antagonist protocols.

Early ovarian hyperstimulation syndrome is completely prevented by gonadotropin releasing-hormone agonist triggering in high-risk oocyte donor cycles: a prospective, luteal-phase follow-up study.

In this prospective, follow-up study of 102 high-risk oocyte donors in their luteal phase, we found a complete absence of ovarian hyperstimulation syndrome (no signs of hemoconcentration or ascites) after the donors were triggered with a gonadotropin releasing-hormone (GnRH) agonist. Due to its powerful preventive effect, the GnRH antagonist protocol combined with a GnRH agonist trigger should preferentially be used in egg donors; in conjunction with an effective luteal support or embryo cryopreservation, the protocol could also be applied to high-risk in vitro fertilization patients.