Selection of first in vitro fertilization cycle stimulation protocol for good prognosis patients: gonadotropin releasing hormone antagonist versus agonist protocols.

OBJECTIVE: The objective of this study was to compare outcome parameters in patients anticipated to have a good response to stimulation based upon baseline characteristics using either a gonadotropin releasing hormone (GnRH) agonist or antagonist protocol in their first in vitro fertilization (IVF) cycle. STUDY DESIGN: A retrospective chart review of all first-time IVF cycles performed during the time period 2005 through 2007 in an academic teaching center. Patients <40 years of age with a normal baseline follicle stimulating hormone (<10 mIU/mL) and normal antral follicle counts (> or = 3 in each ovary) were included. All patients studied were undergoing their first IVF cycle. The main outcome measures were clinical pregnancy and live birth rates. RESULTS: Included in the study were 755 patients undergoing a GnRH agonist protocol and 378 patients undergoing a GnRH antagonist cycle. Implantation rates (39.4% vs. 39.5%), cancellation rates (22.4% vs. 19.2%), clinical pregnancy rates (43.6% vs. 48.6%) and live birth rates (34.9% vs. 40.1%) were similar between GnRH antagonist and GnRH agonist protocol groups, respectively. CONCLUSION: Clinical pregnancy and live birth rates are similar in good responders utilizing either a GnRH agonist or antagonist during their first cycle of IVF.

The Stanford Microarray Database: implementation of new analysis tools and open source release of software.

The Stanford Microarray Database (SMD; http://smd.stanford.edu/) is a research tool and archive that allows hundreds of researchers worldwide to store, annotate, analyze and share data generated by microarray technology. SMD supports most major microarray platforms, and is MIAME-supportive and can export or import MAGE-ML. The primary mission of SMD is to be a research tool that supports researchers from the point of data generation to data publication and dissemination, but it also provides unrestricted access to analysis tools and public data from 300 publications. In addition to supporting ongoing research, SMD makes its source code fully and freely available to others under an Open Source license, enabling other groups to create a local installation of SMD. In this article, we describe several data analysis tools implemented in SMD and we discuss features of our software release.

Should biodiversity and nature have to earn their keep? What it really means to bring environmental goods into the marketplace.

Pursuit of economic gain has sponsored much of our planet's despoliation. Yet conservation increasingly operates as an economic sector that markets biodiversity, ecosystems, and nature as natural capital, service provider, or option value. This essay first elucidates what basic moral theory says about the principle that the goodness of biodiversity and nature is largely economic. It explains why economic valuations may be morally unimportant, inapt for environmental goods, and subversive of more important ideals. It also shows why neither econometric notions of option value nor Daniel Faith's qualitative one credibly applies. The essay then turns to what an economic conception of goodness implies for conservation practice. It refers to two prominent conservation organizations, whose conservation principles match the market-based ones of the World Business Council on Sustainable Development's. The environmental record of the latter organization's practices according to these principles predicts what their adoption for conservation entails.

A simple spreadsheet-based, MIAME-supportive format for microarray data: MAGE-TAB.

BACKGROUND: Sharing of microarray data within the research community has been greatly facilitated by the development of the disclosure and communication standards MIAME and MAGE-ML by the MGED Society. However, the complexity of the MAGE-ML format has made its use impractical for laboratories lacking dedicated bioinformatics support. RESULTS: We propose a simple tab-delimited, spreadsheet-based format, MAGE-TAB, which will become a part of the MAGE microarray data standard and can be used for annotating and communicating microarray data in a MIAME compliant fashion. CONCLUSION: MAGE-TAB will enable laboratories without bioinformatics experience or support to manage, exchange and submit well-annotated microarray data in a standard format using a spreadsheet. The MAGE-TAB format is self-contained, and does not require an understanding of MAGE-ML or XML.

Obstetrical complications in gestational carrier pregnancies.

OBJECTIVE: To report two cases of severe obstetrical complications in gestational carrier pregnancies and to review our clinical experience and compare our results with those reported in the literature. DESIGN: Retrospective analysis. SETTING: A university IVF program. PATIENT(S): Women without a functioning uterus or those whose pregnancy would exacerbate a medical condition were enrolled in the gestational carrier pregnancy program. INTERVENTION(S): IVF cycles using oocytes from genetic mothers (or oocyte donors) were performed, with ET to gestational carriers. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates, obstetrical complications, and neonatal outcomes. RESULT(S): Ten couples underwent a total of 13 cycles using gestational carriers. A clinical pregnancy rate of 69% (9/13) was achieved. An intrapartum hysterectomy and a late puerperal hysterectomy were required because of severe obstetrical complications. The late puerperal hysterectomy was performed for placenta accreta in a triplet gestation. This carrier sustained multiple cerebral infarcts and blindness. One triplet infant died secondary to a hypoplastic left ventricle and complications of prematurity. A second gestational carrier with a singleton gestation underwent a hysterectomy for a uterine rupture, and the infant has cerebral palsy. CONCLUSION(S): The past medical and obstetrical histories of potential gestational carriers must be closely scrutinized, and candidates must be thoroughly counseled about the potential risks involved in the procedure.

Septate uterus with cervical duplication: a full-term delivery after resection of a vaginal septum.

We report a full-term delivery after resection of a longitudinal vaginal septum in a patient with a septate uterus and cervical duplication.

An unusual anatomic variation of a unicornuate uterus with normal external uterine morphology.

OBJECTIVE: To describe a case of a unicornuate uterus with a normal external uterine morphology. DESIGN: Case report. SETTING: University-based fertility center. PATIENT(S): A 30-year-old nulligravid woman with a 1-year history of infertility found to have a right proximal tubal occlusion on hysterosalpingogram. INTERVENTION(S): Laparoscopy, hysteroscopy, and magnetic resonance imaging. MAIN OUTCOME MEASURE(S): External and internal morphology of the uterus. RESULT(S): Laparoscopy showed a normal external uterine morphology and normal fallopian tubes and ovaries, but chromopertubation failed to demonstrate a fill and spill from the right fallopian tube. Hysteroscopy showed a single tubular uterine cavity projecting to the left with a single left tubal ostium, consistent with a unicornuate uterus. Magnetic resonance imaging confirmed a normal external uterine fundal contour and an internal uterine morphology consistent with a unicornuate uterus. CONCLUSION(S): This is the first reported case of a unicornuate uterus presenting with a normal external uterine morphology and an internal morphology consistent with a unicornuate uterus, and we propose inclusion of this anomaly in the classification of mullerian anomalies.

Reducing the dose of human chorionic gonadotropin in high responders does not affect the outcomes of in vitro fertilization.

OBJECTIVE: The lowest effective hCG dose in high responders during IVF-embryo transfer (ET) has not been established. This study was performed to confirm that a dose of 3,300 IU is sufficient to provide adequate oocyte maturation and fertilization. DESIGN: Retrospective review of IVF clinical data. SETTING: Infertility center at a tertiary care university. PATIENT(S): Ninety-four IVF cycles were analyzed from high responders based on peak E(2) levels. Demographics were compared including age, diagnosis, and stimulation protocol. INTERVENTION(S): On the day of hCG administration, if E(2) levels were >/=2,500 but <4,000 pg/mL, patients received 5,000 IU (group A). For levels between 4,000 pg/mL and 5,500 IU pg/mL, they received 3,300 IU (group B). MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, proportion of mature oocytes, fertilization rates, chemical and clinical pregnancy rates (PR). The incidence and severity of ovarian hyperstimulation syndrome (OHSS) was also analyzed. RESULT(S): Mean ages were 35.4 +/- 0.7 and 33.2 +/- 0.7 for groups A and B, respectively. Peak E(2) levels differed significantly (2,907 +/- 76 vs. 4,260 +/- 129 pg/mL), as well as the mean number of eggs retrieved (15.9 +/- 0.9 vs. 20.3 +/- 1.2). Proportion of mature eggs (81.6% vs. 81.9%), fertilization rate (70.5% vs. 68.7%), chemical PR (58.7% vs. 58.7%), and clinical PR (50.0% vs. 43.5%) were similar. There was no difference in the incidence of mild, moderate, or severe OHSS. CONCLUSION(S): A reduced hCG dose of 3,300 IU results in a similar proportion of mature eggs, similar fertilization rates, and similar PRs compared to 5,000 IU. Reducing the dose of hCG does not eliminate the risk of OHSS in a high-risk group.

Gonadotropin-releasing hormone agonist to induce final oocyte maturation prevents the development of ovarian hyperstimulation syndrome in high-risk patients and leads to improved clinical outcomes compared with coasting.

Ninety-four women undergoing IVF with peak E2 level>4000 pg/mL received leuprolide acetate (LA) trigger (LA trigger group) or had gonadotropins withheld for one or more days (coasting group) followed by hCG trigger, unless cycle cancellation occurred. There were no cases of ovarian hyperstimulation syndrome in either group, and the LA trigger group had significantly more oocytes retrieved (26.9+/-9.5 vs. 17.7+/-9.3) P<0.001, more normally fertilized oocytes (15.0+/-7.8 vs. 10.3+/-6.3) P=0.01, and higher clinical and ongoing pregnancy rates than the coasting group (52.5% vs. 27.2%; 49.2% vs. 24.2%, P=0.02 for both comparisons, respectively).

Predictive value of embryo grading for embryos with known outcomes.

OBJECTIVE: To compare pronuclear morphology (Z-score), day 3 embryo grade, and day 3 cell number in the prediction of successful implantation rates (IRs), including cycles in which all or none of the embryos implanted. DESIGN: Retrospective analysis. SETTING: University-based IVF center. PATIENT(S): Four hundred twenty-six fresh IVF day 3 transfers of 852 embryos in women <36 years of age from January 2000 to December 2003 in whom all or none of the embryos implanted. MAIN OUTCOME MEASURE(S): Evaluation of Z-scores, embryo morphology, cell number, and IR. RESULT(S): Day 3 parameters were more predictive than Z-scores. When early parameters were poor (Z-score) but late parameters were both good, the IR was 38%, compared with 4% when the Z-score was good but the late parameters were poor. CONCLUSION(S): Embryo grading systems are useful in the prediction of embryo implantation. In particular, cell number and embryo grade are more predictive than Z-scores. Therefore, late parameters have a better prognostic value than Z-scores when selecting embryos for transfer.

Transfer of two versus three embryos in women less than 40 years old undergoing frozen transfer cycles.

OBJECTIVE: To compare outcomes of frozen embryo transfer (FET) cycles when two or three embryos were transferred in women aged <40 years. DESIGN: Retrospective chart review. SETTING: A university-affiliated IVF program. PATIENT(S): Women undergoing FET cycles between January 2004 and December 2005. INTERVENTION(S): Transfer of two or three embryos. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (PR), multiple pregnancy rate (MPR), and live birth rate (LBR). RESULT(S): In patients aged <35 (n = 145), two versus three embryo group had similar PR and LBR, but the MPR was significantly higher in the three-embryo group (41% for three embryos vs. 9.4% for two embryos). Clinical pregnancy in the fresh cycle from which the frozen embryos were obtained did not affect the PR, and an increase in MPR was still observed. In patients aged 35 to 39 (n = 93), there were no differences in the PR, MPR, or LBR between the two groups. CONCLUSION(S): Transfer of two instead of three frozen embryos in patients <35 years old resulted in a significant decrease in MPR without compromising PR or LBR. Transferring additional embryos when a patient had an unsuccessful fresh cycle was not warranted. In the age group 35-39 years, transferring two instead of three embryos did not decrease PR or LBR, and had no effect on the risk of high-order multiples.

Maturation, fertilization, and the structure and function of the endoplasmic reticulum in cryopreserved mouse oocytes.

Oocyte cryopreservation is a promising technology that could benefit women undergoing assisted reproduction. Most studies examining the effects of cryopreservation on fertilization and developmental competence have been done using metaphase II-stage oocytes, while fewer studies have focused on freezing oocytes at the germinal vesicle (GV) stage, followed by in vitro maturation. Herein, we examined the effects of vitrifying GV-stage mouse oocytes on cytoplasmic structure and on the ability to undergo cytoplasmic changes necessary for proper fertilization and early embryonic development. We examined the endoplasmic reticulum (ER) as one indicator of cytoplasmic structure, as well as the ability of oocytes to develop Ca(2+) release mechanisms following vitrification and in vitro maturation. Vitrified GV-stage oocytes matured in culture to metaphase II at a rate comparable to that of controls. These oocytes had the capacity to release Ca(2+) following injection of inositol 1,4,5-trisphosphate, demonstrating that Ca(2+) release mechanisms developed during meiotic maturation. The ER remained intact during the vitrification procedure as assessed using the lipophilic fluorescent dye DiI. However, the reorganization of the ER that occurs during in vivo maturation was impaired in oocytes that were vitrified before oocyte maturation. These results show that vitrification of GV-stage oocytes does not affect nuclear maturation or the continuity of the ER, but normal cytoplasmic maturation as assessed by the reorganization of the ER is disrupted. Deficiencies in factors that are responsible for proper ER reorganization during oocyte maturation could contribute to the low developmental potential previously reported in vitrified in vitro-matured oocytes.

Comparison of luteal estradiol patch and gonadotropin-releasing hormone antagonist suppression protocol before gonadotropin stimulation versus microdose gonadotropin-releasing hormone agonist protocol for patients with a history of poor in vitro fertilization outcomes.

OBJECTIVE: To compare IVF outcomes in poor-responder patients undergoing stimulation after luteal phase E(2) patch/GnRH antagonist (LPG) protocol versus microdose GnRH agonist protocol. DESIGN: Retrospective analysis. SETTING: University-based IVF center. PATIENT(S): Forty-five women undergoing ovarian stimulation for IVF using the LPG protocol were compared with 76 women stimulated with the microdose GnRH agonist protocol from May 2005 to April 2006. MAIN OUTCOME MEASURE(S): Cancellation rate, number of oocytes retrieved, and clinical pregnancy rates. RESULT(S): The mean number of oocytes (9.1 +/- 4.1 vs. 8.9 +/- 4.3) and mature oocytes (6.7 +/- 3.5 vs. 6.8 +/- 3.1) retrieved were similar, as were the fertilization rates (70.0% +/- 24.2% vs. 69.9% +/- 21.5%) and the number of embryos transferred (2.5 +/- 1.1 vs. 2.7 +/- 1.3). The cancellation rate was not significantly different between the groups (13/45, 28.9% vs. 23/76, 30.3%). Likewise, there were no significant differences among the implantation rate (15.0% vs. 12.5%), clinical pregnancy rate (43.3% vs. 45.1%), and ongoing pregnancy rate per transfer (33.3% vs. 26.0%) between both groups. CONCLUSION(S): This study demonstrates that the use of an E(2) patch and a GnRH antagonist during the preceding luteal phase in patients with a history of failed cycles can provide similar IVF outcomes when compared with the microdose GnRH agonist protocol.

Ruptured ectopic pregnancy with contralateral adnexal torsion after spontaneous conception.

OBJECTIVE: To describe a case of ruptured ectopic pregnancy and contralateral adnexal torsion after spontaneous conception. DESIGN: Case report. SETTING: Tertiary university medical center. PATIENT(S): A 23-year-old multiparous female with severe bilateral pelvic pain and a positive pregnancy test. INTERVENTION(S): Operative laparoscopy with detorsion of left adnexa, drainage of left ovarian hemorrhagic corpus luteum cyst, right salpingectomy, and dilation and curettage. MAIN OUTCOME MEASURE(S): Laparoscopy revealed a 5 cm hemorrhagic corpus luteum cyst of the left ovary, torsion of the left ovary and fallopian tube, and a ruptured right ampullary ectopic pregnancy. RESULT(S): Normal perfusion of left ovary and fallopian tube after detorsion, resolution of left ovarian hemorrhagic corpus luteum cyst, patent left fallopian tube with chromopertubation, and successful removal of ectopic pregnancy. CONCLUSION(S): This is a unique case of adnexal torsion and contralateral ectopic pregnancy occurring after spontaneous conception.

Meiotic arrest in human oocytes is maintained by a Gs signaling pathway.

In mammalian oocytes, the maintenance of meiotic prophase I arrest prior to the surge of LH that stimulates meiotic maturation depends on a high level of cAMP within the oocyte. In mouse and rat, the cAMP is generated in the oocyte, and this requires the activity of a constitutively active, Gs-linked receptor, GPR3 or GPR12, respectively. To examine if human oocyte meiotic arrest depends on a similar pathway, we used RT-PCR and Western blotting to look at whether human oocytes express the same components for maintaining arrest as rodent oocytes. RNA encoding GPR3, but not GPR12, was expressed. RNA encoding adenylate cyclase type 3, which is the major adenylate cyclase required for maintaining meiotic arrest in the mouse oocyte, was also expressed, as was Galphas protein. To determine if this pathway is functional in the human oocyte, we examined the effect of injecting a function-blocking antibody against Galphas on meiotic resumption. This antibody stimulated meiotic resumption of human oocytes that were maintained at the prophase I stage using a phosphodiesterase inhibitor. These results demonstrate that human oocytes maintain meiotic arrest prior to the LH surge using a signaling pathway similar to that of rodent oocytes.

Prevention of recurrent adnexal torsion.

OBJECTIVE: To report a case of adnexal torsion after in vitro fertilization (IVF) with two subsequent episodes of contralateral adnexal torsion and a novel approach for reducing the risk of recurrence. DESIGN: Case report. SETTING: University-based IVF program. PATIENT(S): A 32-year-old woman who conceived with IVF and experienced sequential bilateral adnexal torsion. Left adnexal torsion was diagnosed with laparoscopic detorsion performed 2 days after embryo transfer. At 7 weeks' gestation, right adnexal torsion occurred and was managed with laparoscopic detorsion. Subsequently, right adnexal torsion recurred at 10 weeks' gestation, and laparoscopic detorsion with shortening of the uteroovarian ligament was performed. INTERVENTION(S): Gonadotropin ovulation induction, IVF, and laparoscopic detorsion of both right and left adnexa with shortening of the right uteroovarian ligament. MAIN OUTCOME MEASURE(S): Preservation of adnexa after torsion and successful pregnancy. RESULT(S): Successful pregnancy and birth; resolution of torsion, prevention of recurrence with viable bilateral adnexa after detorsion and shortening of the utero-ovarian ligament with novel use of laparoscopic Endoloop. CONCLUSION(S): This is a unique case of multiple episodes of adnexal torsion following IVF with a new form of treatment using the laparoscopic Endoloop. Management of the infertility patient should be conservative and warrants ovarian preservation whenever possible. Multiple sequential episodes of adnexal torsion during a single pregnancy are a rare complication of IVF. Shortening of the utero-ovarian ligament is an alternative to oophoropexy to prevent recurrence.

The effect of luteal phase vaginal estradiol supplementation on the success of in vitro fertilization treatment: a prospective randomized study.

OBJECTIVE: To determine whether the use of luteal phase vaginal E(2) supplementation improves clinical pregnancy rates in patients undergoing IVF treatment. DESIGN: Prospective randomized controlled trial. SETTING: University-based tertiary fertility center. PATIENT(S): One hundred sixty-six patients undergoing their first cycle of IVF treatment. INTERVENTION(S): Patients underwent three different protocols for controlled ovarian hyperstimulation for IVF treatment with long GnRH agonist suppression, use of GnRH antagonist, or a microdose GnRH agonist protocol. Luteal phase support was in the form of IM P. Patients randomized into the study group (n = 84) received E(2) supplementation in the form of vaginal estrace 2 mg twice a day starting on the day of ET. Patients randomized to the control group (n = 82) received no E(2) supplementation. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): There were no significant differences in the implantation (56/210 [26.7%] vs. 64/203 [31.5%]), clinical pregnancy (42/84 [50%] vs. 52/82 [63.4%]), and ongoing pregnancy rates (40/84 [47.6%] vs. 46/82 [56.1%]) between the study and control groups, respectively. In the subgroup of patients who used the long GnRH agonist suppression protocol, there was a lower clinical pregnancy rate in the study group compared with the control group (27/55 [49.1%] vs. 42/59 [71.2%]). There were, however, no differences in clinical pregnancy rates between the two groups in patients who used either the GnRH antagonist or microdose GnRH agonist protocols. CONCLUSION(S): The addition of vaginal E(2) supplementation to routine P supplementation for luteal support does not improve the probability of conception after IVF treatment.

The use of gonadotropin-releasing hormone (GnRH) agonist to induce oocyte maturation after cotreatment with GnRH antagonist in high-risk patients undergoing in vitro fertilization prevents the risk of ovarian hyperstimulation syndrome: a prospective randomized controlled study.

OBJECTIVE: To determine whether there are any differences in the incidence of ovarian hyperstimulation syndrome (OHSS) and implantation rates in high-risk patients undergoing IVF using a protocol consisting of GnRH agonist trigger after cotreatment with GnRH antagonist or hCG trigger after dual pituitary suppression protocol. DESIGN: Prospective randomized controlled trial. SETTING: University-based tertiary fertility center. PATIENT(S): Sixty-six patients under 40 years of age with polycystic ovarian syndrome, polycystic ovarian morphology, or previous high response undergoing IVF. INTERVENTION(S): Patients were randomized to an ovarian stimulation protocol consisting of either GnRH agonist trigger after cotreatment with GnRH antagonist (study group) or hCG trigger after dual pituitary suppression with a GnRH agonist (control group). Both groups received luteal phase and early pregnancy supplementation with IM progesterone (P), and patients in the study group also received E(2) patches and their doses were adjusted according to the serum levels. MAIN OUTCOME MEASURE(S): Incidence of OHSS and implantation rate. RESULT(S): None of the patients in the study group developed any form of OHSS compared with 31% (10/32) of the patients in the control group. There were no significant differences in the implantation (22/61 [36.0%] vs. 20/64 [31.0%]), clinical pregnancy (17/30 [56.7%] vs. 15/29 [51.7%]), and ongoing pregnancy rates (16/30 [53.3%] vs. 14/29 [48.3%]) between the study and control groups, respectively. CONCLUSION(S): The use of a protocol consisting of GnRH agonist trigger after GnRH antagonist cotreatment combined with adequate luteal phase and early pregnancy E(2) and P supplementation reduces the risk of OHSS in high-risk patients undergoing IVF without affecting implantation rate.

Impact of leuprolide acetate on luteal phase function in women undergoing controlled ovarian hyperstimulation and intrauterine insemination.

OBJECTIVE: To determine if the combination of leuprolide acetate (LA) and human menopausal gonadotropin (hMG) results in luteal phase dysfunction. DESIGN: A prospective, randomized clinical trial. SETTING: A tertiary care university fertility center. PATIENT(S): One hundred thirty-five couples with various etiologies of infertility. INTERVENTION(S): Patients were prospectively randomized to receive either hMG and intrauterine insemination (IUI) or luteal phase down-regulation with LA, hMG, and IUI. MAIN OUTCOME MEASURE(S): Serum luteal phase progesterone (P) and luteal phase estradiol (E2) were obtained 9 days after hCG administration. Twenty-four-hour urinary P and luteinizing hormone (LH) were analyzed 9 days after human chorionic gonadotropin (hCG). Endometrial biopsies were performed 11 days after hCG and evaluated for luteal phase defects (LPD) using Noyes' criteria. RESULT(S): No significant differences in the incidence of LPD (11.9% vs. 13.9%), cycle fecundity (16.6% vs. 16.3%), or luteal phase hormone profiles were observed between the groups receiving and not receiving LA. A significant difference in E2 levels (on the day of hCG administration) between cycles with a luteal phase defect (967 pg/mL +/- 106) and without a luteal phase defect (1,422 pg/mL +/- 83) was observed (P<.05). CONCLUSION(S): Pituitary down-regulation with LA combined with hMG did not result in luteal phase dysfunction. The E2 levels on the day of hCG administration in both groups were lower in women with documented luteal phase defects.