S.E. Lanzendorf

Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization

OBJECTIVE To determine if follicular free fatty acid (FFA) levels are associated with cumulus oocyte complex (COC) morphology. DESIGN Prospective cohort study. SETTING University in vitro fertilization (IVF) practice. PATIENT(S) A total of 102 women undergoing IVF. INTERVENTION(S) Measurement of FFAs in serum and ovarian follicular fluid. MAIN OUTCOME MEASURE(S) Total and specific follicular and serum FFA levels, correlations between follicular and serum FFAs, and associations between follicular FFA levels and markers of oocyte quality, including COC morphology. RESULT(S) Predominant follicular fluid and serum FFAs were oleic, palmitic, linoleic, and stearic acids. Correlations between follicular and serum FFA concentrations were weak (r=0.252, 0.288, 0.236, 0.309, respectively for specific FFAs; r=0.212 for total FFAs). A receiver operating characteristic curve determined total follicular FFAs≥0.232 μmol/mL distinguished women with a lower versus higher percentage of COCs with favorable morphology. Women with elevated follicular FFAs (n=31) were more likely to have COCs with poor morphology than others (n=71; OR 3.3, 95% CI1.2-9.2). This relationship held after adjusting for potential confounders, including age, body mass index, endometriosis, and amount of gonadotropin administered (β=1.2; OR 3.4, 95% CI 1.1-10.4). CONCLUSION(S) Elevated follicular FFA levels are associated with poor COC morphology. Further work is needed to determine what factors influence follicular FFA levels and if these factors impact fertility.

Morbid obesity is associated with lower clinical pregnancy rates after in vitro fertilization in women with polycystic ovary syndrome

OBJECTIVE To determine whether morbid obesity is associated with decreased pregnancy and live birth rates after IVF in women with polycystic ovary syndrome (PCOS). DESIGN Retrospective cohort study. SETTING University-based fertility center. PATIENT(S) Seventy-two women with PCOS who completed their first IVF cycle between 2001 and 2006. INTERVENTION(S) Outcomes of IVF were compared between women with a body mass index (BMI) of <40 kg/m(2) vs. those with a BMI of > or =40 kg/m(2). MAIN OUTCOME MEASURE(S) Clinical pregnancy rate, live birth rate. RESULT(S) Morbidly obese women with PCOS (n = 19) had significantly lower clinical pregnancy rates after IVF than patients with PCOS who were not morbidly obese (n = 53) (32% vs. 72%, relative risk 0.44, 95% confidence interval 0.22-0.87). Their live birth rates were lower too, although this difference was not statistically significant (32% vs. 60%, relative risk 0.52, 95% confidence interval 0.26-1.05). CONCLUSION(S) Morbid obesity is associated with lower pregnancy rates in women with PCOS after IVF, raising the question of whether weight loss may improve IVF success rates for morbidly obese PCOS patients.

Polycystic ovary syndrome and maternal obesity affect oocyte size in in vitro fertilization/intracytoplasmic sperm injection cycles

To determine the impact of maternal metabolic state on oocyte development in women undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), we retrospectively analyzed a cohort of women with PCOS undergoing IVF/ICSI from 2008-2009 in a university-based fertility center. We determined that women with PCOS and obesity have smaller oocytes than control subjects, and that when further subdivided by body mass index, both PCOS and obesity independently influence oocyte size.

A prospective, randomized, double-blinded study of assisted hatching in women younger than 38 years undergoing in vitro fertilization

OBJECTIVE To determine whether assisted hatching is beneficial to IVF patients younger than 38 years whose embryos have a thickened zona pellucida (ZP). DESIGN Prospective, randomized, double-blinded, crossover study. SETTING University-based infertility center. PATIENT(S) One hundred twenty-one women less than 38 years of age, undergoing IVF at Washington University between April 2004 and February 2007, with ZP thickness > or =13 microm for any embryos. INTERVENTION(S) Measurement of ZP thickness in embryos undergoing IVF; randomization of women with embryos with ZP thickness > or =13 microm to no procedure or assisted hatching performed by acidic Tyrodes solution. MAIN OUTCOME MEASURE(S) Clinical intrauterine pregnancy rate, implantation rate, spontaneous pregnancy loss, and live birth rate. RESULT(S) Baseline characteristics and ZP thickness were not significantly different between the two study arms (hatched and unhatched). No significant differences were observed between hatched and unhatched patients in the rates of clinical pregnancy (47% vs. 50% respectively) or live birth (46% vs. 45% respectively). Further, no significant differences were noted between hatched and unhatched groups in rates of spontaneous abortions, monozygotic twinning, dizygotic twinning, chromosomal abnormalities, or ectopic gestations. In addition, mean ZP thickness did not have a significant effect on pregnancy. CONCLUSION(S) In patients younger than 38 years with embryos with ZP thickness of > or =13 microm, assisted hatching does not improve the rates of implantation, clinical pregnancy, or live birth, and thus does not appear to offer any benefit to patients in this age group undergoing IVF.

Randomized controlled study of human zona pellucida dissection using the Zona Infrared Laser Optical System: evaluation of blastomere damage, embryo development, and subsequent hatching

OBJECTIVE To assess the effect of laser hatching on human embryo damage and subsequent development using the Zona Infrared Laser Optical System (ZILOS). DESIGN Randomized controlled study. SETTING Tertiary care fertility clinic. PATIENT(S) One hundred fourteen donated and discarded frozen human embryos. INTERVENTION(S) Embryos were thawed, cultured with cleavage and morphology evaluated periodically, and randomized into control, partial hatching, or complete hatching groups. The laser hatching procedure was performed by ZILOS. Zona thickness and embryo diameter were recorded. Complete hatching involved the production of a full-thickness defect in the zona and partial hatching, a defect in the outer half of the zona. No laser treatment was administered to the control group. MAIN OUTCOME MEASURE(S) Blastocyst development and completion of hatching process. RESULT(S) No significant difference was noted between the three study groups for their baseline characteristics. There was no significant difference in blastocyst development among the three groups. However, the complete hatching group showed a significant increase in hatching compared to the control group. CONCLUSION(S) Complete laser hatching of human embryos using the ZILOS does not have an adverse effect on subsequent development and increases the rate of completion of hatching.

Sperm banking for fertility preservation: a 20-year experience.

OBJECTIVE Sperm banking is an effective method to preserve fertility, but is not universally offered to males facing gonadotoxic treatment in the United States. We compared the disposition and semen parameters of cryopreserved sperm from individuals referred for sperm banking secondary to a cancer diagnosis to those of sperm from men banking for infertility reasons. STUDY DESIGN We performed a retrospective cohort study that reviewed 1118 records from males who presented to bank sperm at Washington University between 1991 and 2010. We collected and analyzed demographics, semen parameters, and disposition of banked sperm. RESULTS Four hundred and twenty-three men with cancer and 348 banking for infertility reasons attempted sperm cryopreservation in our unit during the specified time period. The most prevalent cancers in our cohort were testicular (32%), lymphoma (25%), and leukemia (11%). Patients with leukemia had the lowest pre-thaw counts and motility. Most cancer patients (57%) who banked elected to use, transfer to another facility, or keep their specimens in storage. The remaining samples were discarded electively (34%) or following death (8%). Overall semen parameters were similar between the cancer and infertility groups, but demographics, ability to bank a sample, azoospermia rates, length of storage, current banking status, and use of banked sperm differed significantly between the two groups. CONCLUSIONS The majority of cancer patients who banked survived their cancer and chose to continue storage of banked samples. Cancer patients were more likely than infertility patients to use or continue storage of banked samples. Our study provides evidence that sperm banking is a utilized modality of fertility preservation in patients with a myriad of cancer diagnoses and should be offered to all men facing gonadotoxic therapies. Further work is needed to determine where disparities in access to sperm banking exist to improve the potential for future fertility in these males.

Sperm Recovery and IVF after Testicular Sperm Extraction (TESE): Effect of Male Diagnosis and Use of Off-Site Surgical Centers on Sperm Recovery and IVF

Objective Determine whether testicular sperm extractions and pregnancy outcomes are influenced by male and female infertility diagnoses, location of surgical center and time to cryopreservation. Patients One hundred and thirty men undergoing testicular sperm extraction and 76 couples undergoing 123 in vitro fertilization cycles with testicular sperm. Outcome Measures Successful sperm recovery defined as 1–2 sperm/0.5 mL by diagnosis including obstructive azoospermia (n = 60), non-obstructive azoospermia (n = 39), cancer (n = 14), paralysis (n = 7) and other (n = 10). Obstructive azoospermia was analyzed as congenital absence of the vas deferens (n = 22), vasectomy or failed vasectomy reversal (n = 37) and “other”(n = 1). Sperm recovery was also evaluated by surgical site including infertility clinic (n = 54), hospital operating room (n = 67) and physician’s office (n = 11). Treatment cycles were evaluated for number of oocytes, fertilization, embryo quality, implantation rate and clinical/ongoing pregnancies as related to male diagnosis, female diagnosis, and use of fresh or cryopreserved testicular sperm. Results Testicular sperm recovery from azoospermic males with all diagnoses was high (70 to 100%) except non-obstructive azoospermia (31%) and was not influenced by distance from surgical center to laboratory. Following in vitro fertilization, rate of fertilization was significantly lower with non-obstructive azoospermia (43%, p = <0.0001) compared to other male diagnoses (66%, p = <0.0001, 59% p = 0.015). No differences were noted in clinical pregnancy rate by male diagnosis; however, the delivery rate per cycle was significantly higher with obstructive azoospermia (38% p = 0.0371) compared to diagnoses of cancer, paralysis or other (16.7%). Women diagnosed with diminished ovarian reserve had a reduced clinical pregnancy rate (7.4% p = 0.007) compared to those with other diagnoses (44%). Conclusion Testicular sperm extraction is a safe and effective option regardless of the etiology of the azoospermia. The type of surgical center and/or its distance from the laboratory was not related to success. Men with non-obstructive azoospermia have a lower chance of successful sperm retrieval and fertilization.

Encouraging patient-driven single-embryo transfer

Single-embryo transfer (SET) removes the risk of multiples in in vitro fertilization (IVF), but women with unfavorable IVF prognosis have been dissuaded from SET despite their desire to avoid multiples. In our clinic, 54% of the women who requested SET delivered healthy singletons, even though only two of them had met the American Society for Reproductive Medicines SET guidelines. This demonstrates the value of encouraging patient-driven SET.