J. Nulsen

A comparative analysis of the cycle fecundity rates associated with combined human menopausal gonadotropin (hMG) and intrauterine insemination (IUI) versus either hMG or IUI alone

Human menopausal gonadotropin (hMG) superovulation combined with washed intrauterine insemination (IUI) has been advocated for the treatment of various forms of infertility when more traditional therapy has failed. To assess the relative efficacy of combined treatment with hMG and IUI compared with either hMG or IUI alone, pregnancy outcomes of the three treatment groups were compared in couples having infertility because of male factor, cervical factor, endometriosis, or unexplained. A total of 751 cycles were analyzed from 322 couples. The mean cycle fecundity rate associated with hMG/IUI therapy was significantly higher than either hMG or IUI therapy alone for all patients (hMG/IUI = 19.6%, hMG = 6.3%, IUI = 3.4%). The improvement in cycle fecundity rates with hMG/IUI therapy was also observed when the couples were separated by infertility diagnostic groups: male factor (hMG/IUI = 15.3%, hMG = 4.4%, IUI = 3.0%), cervical factor (hMG/IUI = 26.3%, hMG = 7.9%, IUI = 5.1%), endometriosis (hMG/IUI = 12.85%, hMG = 6.6%), and unexplained infertility (hMG/IUI = 32.6%, hMG = 5.5%, IUI = 0%). Moreover, in patients who had failed to conceive with hMG or IUI alone, the cycle fecundity rate when they were switched to hMG/IUI therapy equaled that of patients who received combined therapy from the onset. We conclude that cycle fecundity rates and cumulative pregnancy rates are significantly greater using a combination of hMG and IUI compared with either modality alone in the treatment of male factor, cervical factor, endometriosis, or unexplained infertility. Indeed, in couples with nontubal related infertility, cycle fecundity rates with hMG/IUI approach the rates seen with in vitro fertilization and gamete intrafallopian tube transfer.

Chronic endometritis is a frequent finding in women with recurrent implantation failure after in vitro fertilization

OBJECTIVE To determine the role of endometrial sampling for identification and treatment of chronic endometritis (CE) in patients undergoing IVF-ET who repeatedly failed to conceive despite the transfer of good-quality embryos. DESIGN Retrospective chart review. SETTING University-based tertiary fertility center. PATIENT(S) Thirty-three patients with recurrent implantation failure (RIF) who underwent endometrial sampling and subsequent ET were analyzed based on immunohistochemically confirmed CE: CE present on biopsy (group 1; n = 10) and CE absent on biopsy (group 2; n = 23). Patients with RIF undergoing IVF cycles during the same time period who did not have endometrial sampling were used as controls (group 3; n = 485). INTERVENTION(S) Endometrial sampling for CE and subsequent antibiotic treatment in affected patients followed by another IVF-ET cycle. RESULT(S) Chronic endometritis was identified in 30.3% of patients with RIF. Group 1 had lower implantation rates (11.5%) in the IVF cycle following treatment than did group 2 and group 3 (32.7% and 20.3%, respectively). Clinical pregnancy and ongoing pregnancy rates were similar across groups. CONCLUSION(S) Recurrent implantation failure warrants investigation of CE as a contributing factor. Women demonstrating CE on endometrial sampling have lower implantation rates in a subsequent IVF-ET cycle; however, there were no differences in subsequent clinical pregnancy or ongoing pregnancy rates after successful antibiotic treatment.

Dual trigger of oocyte maturation with gonadotropin-releasing hormone agonist and low-dose human chorionic gonadotropin to optimize live birth rates in high responders

OBJECTIVE To compare live birth rates after dual trigger of oocyte maturation with GnRH agonist (GnRHa) and low-dose hCG versus GnRHa alone in high responders with peak E(2) <4,000 pg/mL at risk of ovarian hyperstimulation syndrome (OHSS). DESIGN Retrospective cohort study. SETTING University-based tertiary-care fertility center. PATIENT(S) Patients <40 years old with peak E(2) <4,000 pg/mL at risk of OHSS who underwent IVF/intracytoplasmic sperm injection with GnRH antagonist protocol and triggered with GnRHa alone or GnRHa plus 1,000 IU hCG (dual trigger) for oocyte maturation. INTERVENTION(S) GnRHa alone versus dual trigger. MAIN OUTCOME MEASURE(S) Live birth, implantation, and clinical pregnancy rates and OHSS. RESULT(S) The dual-trigger group had a significantly higher live birth rate (52.9% vs. 30.9%), implantation rate (41.9% vs. 22.1%), and clinical pregnancy rate (58.8% vs. 36.8%) compared with the GnRHa trigger group. One case of mild OHSS occurred in the dual-trigger group, and there were no cases of OHSS in the GnRHa trigger group. CONCLUSION(S) Dual trigger of oocyte maturation with GnRHa and low-dose hCG in high responders with peak E(2) <4,000 pg/mL improves the probability of conception and live birth without increasing the risk of significant OHSS.

GnRH agonist to induce oocyte maturation during IVF in patients at high risk of OHSS

The aim of this retrospective study was to evaluate the effectiveness of gonadotrophin-releasing hormone agonist (GnRHa) to trigger oocyte maturation in patients with polycystic ovarian syndrome (PCOS) or previous high response. The outcome of ovarian stimulation and IVF in patients using GnRHa to trigger oocyte maturation after co-treatment with GnRH antagonist (study group) was compared with patients using human chorionic gonadotrophin (HCG) to trigger oocyte maturation after a dual pituitary suppression protocol with oral contraceptive pill (OCP) and GnRHa overlap (control group). All patients received intramuscular progesterone for luteal support but patients in the study group received additional supplementation with oestradiol patches. The mean number of oocytes, proportion of mature oocytes and fertilization rate were similar between the study and control groups. Implantation rate (38.6% versus 45.1%), clinical pregnancy rate (69.6% versus 60.9%) and delivery rate (62.5% versus 56.5%) were similar in the study and control groups respectively. There was one case of moderate ovarian hyperstimulation syndrome (OHSS) in the control group and none in the study group. GnRHa is effective in triggering oocyte maturation in patients with PCOS or previous high response. Further randomized studies are required to evaluate its effectiveness in the prevention of OHSS in this group of patients.

The value of increasing the dose of human menopausal gonadotropins in women who initially demonstrate a poor response

OBJECTIVE To evaluate the benefit of increasing the hMG dose in subsequent superovulation cycles for those individuals who demonstrate a poor response on up to three ampules of hMG daily. DESIGN AND SETTING Retrospective analysis of all superovulation cycles at the University of Connecticut Health Center. PATIENTS All women undergoing hMG therapy with IUI from January 1990 until December 1992. INTERVENTIONS All patients were initially stimulated with up to three ampules of hMG daily. All patients who did not conceive on their first hMG cycle and demonstrated a poor response to hMG therapy were started on higher doses of hMG in an effort to obtain a good response. A maximum of eight ampules of hMG per day were used. MAIN OUTCOME MEASURES Peak serum E2, the number of mature preovulatory follicles, and cycle fecundity were compared. RESULTS The poor responders using up to three ampules daily had a peak E2 of 384 +/- 26 pg/mL (1,421 +/- 96 pmol/L), 1.4 +/- 0.1 mature follicles, and a cycle fecundity of 3.1% compared with an E2 of 900 +/- 83 pg/mL (3,330 +/- 307 pmol/L), 2.7 +/- 0.2 mature follicles, and a cycle fecundity of 4.3% when these poor responders had their dose increased to five or more ampules daily. Those individuals demonstrating a good response on less than or equal to three ampules of hMG daily had an average peak E2 of 1,159 +/- 41 pg/mL (4,288 +/- 151 pmol/L), 3.4 +/- 0.2 mature follicles, and a cycle fecundity of 16.5%. CONCLUSIONS Despite significant improvement in peak E2 and the number of mature preovulatory follicles when the hMG dose was increased in poor responders, no significant increase in cycle fecundity was noted.

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.

Cervical mucus changes in relationship to urinary luteinizing hormone

In order to evaluate the relationship between the urinary luteinizing hormone (LH) surge as detected by the OvuSTICK (Monoclonal Antibodies, Inc., Mountain View, CA) method and daily cervical mucus parameters, ten spontaneously ovulating women undergoing infertility evaluation were followed during their cycles with twice daily urinary LH testing as well as daily ultrasound, mucus evaluation, and hormonal assays of serum LH, progesterone (P), and estradiol (E2). Maximal cervical mucus scores, as determined using a modified Insler score, were noted to coincide consistently with the urinary LH surge as detected by twice daily testing and to precede ultrasound evidence of ovulation by 0 to 24 hours. Mucus scores rapidly declined in the 24-hour period following the urinary LH surge. Detection of the urinary LH surge may therefore help identify that period of time during which cervical mucus parameters are optimal and therefore facilitate the timing of artificial insemination, intercourse, or postcoital testing.

Conservative management of interstitial pregnancy

Earlier detection of ectopic pregnancies allows the patient and physician the option of conservative management. Conservative surgical management of ampullary ectopic pregnancies has been well described. Traditional management of interstitial or cornual gestation has been by salpingectomy with or without cornual resection or by hysterectomy. In this paper we present a case report of alternative, less radical surgical management and review the literature on conservative surgical and medical management of interstitial pregnancies.

Effects of gonadotropin-releasing hormone agonists and antagonists on luteal function.

Purpose of review This review addresses the effects of gonadotropin-releasing hormone agonists and antagonists on various aspects of the luteal phase. Recent findings Recent studies have shown that use of both gonadotropin-releasing hormone agonists and antagonists during in-vitro fertilization cycles leads to alterations in the hormonal profiles of the luteal phase as well as changes in endometrial histology. Gonadotropin-releasing hormone agonists are effective in triggering final oocyte maturation and reducing the incidence of ovarian hyperstimulation syndrome. Ongoing pregnancy rates are excellent after gonadotropin-releasing hormone agonist trigger when luteal phase and early pregnancy supplementation with estradiol and progesterone is provided. Gonadotropin-releasing hormone agonists have recently been used for luteal phase support in in-vitro fertilization cycles. Summary Although gonadotropin-releasing hormone agonists and antagonists are clinically useful, they may have adverse effects on luteal function. Luteal phase supplementation significantly improves clinical outcomes in in-vitro fertilization cycles because it may correct some of these detrimental effects. Use of gonadotropin-releasing hormone agonist to induce oocyte maturation is beneficial to patients who are at increased risk for ovarian hyperstimulation syndrome. The key factor in achieving favorable ongoing pregnancy rates with use of gonadotropin-releasing hormone agonist to induce oocyte maturation appears to be adequate luteal phase support.

Intracytoplasmic sperm injection overcomes previous fertilization failure with conventional in vitro fertilization

OBJECTIVE To evaluate the outcome of intracytoplasmic sperm injection (ICSI) in patients with previous idiopathic fertilization failure (< or =20% fertilization rate) after conventional IVF. DESIGN Retrospective analysis. SETTING IVF program at a university medical center. PATIENT(S) Twenty-five patients who underwent 38 ICSI cycles after experiencing unexplained fertilization failure with conventional IVF (group A) and 87 patients who underwent 118 ICSI cycles for male factor indications during the same period (group B). INTERVENTION(S) Intracytoplasmic sperm injection was performed in a subsequent cycle after fertilization failure with conventional IVF. MAIN OUTCOME MEASURE(S) Outcomes of IVF were compared between groups A and B. RESULT(S) Fertilization was achieved with ICSI in all patients with previous fertilization failure. The mean (+/- SD) fertilization rate (68%+/-21% vs. 64%+/-22%), implantation rate per embryo (22.6% vs. 20%), and delivery rate per cycle (47.3% vs. 49.1%) did not differ significantly between groups A and B. Overall, 72% of patients with previous unexplained fertilization failure had a successful pregnancy after ICSI. CONCLUSION(S) Intracytoplasmic sperm injection can overcome unexplained fertilization failure caused by a potentially occult gamete abnormality, with the same fertilization, implantation, and pregnancy rates as are seen in patients with abnormal sperm parameters.