Mark Perloe

Chromatin fluorescence characteristics and standard semen analysis parameters: correlations observed in andrology testing among 136 males referred for infertility evaluation

This paper aims to describe the relation between standard semen analysis parameters (concentration, motility and morphology) and sperm chromatin structure assay (SCSA) results among patients referred for infertility evaluation. Healthy males (n = 136) seeking infertility consultation were evaluated prospectively by semen analysis and sperm chromatin structure assay (SCSA). Significant inverse correlations were observed between high sperm concentration and DNA fragmentation index (DFI) and high DNA stainability (HDS) (r =− 0.45; P < 0.001, and r =− 0.40; P < 0.001, respectively). Both progressive motility and normal morphology were also strongly inversely correlated with DFI and HDS. However, in stratified analysis the correlation between concentration ⩽ 20 M/ml and DFI, and concentration ⩽ 20 M/ml and HDS were not significant (P = 0.31 and 0.38, respectively). For men with sperm motility ⩽ 40% the correlation between motility and HDS was not significant (P = 0.22), but between motility and DFI the correlation remained significant (P = 0.04). Although strong correlations between DFI, HDS and semen analysis findings were noted in the overall study population, when oligozoospermic and asthenozoospermic patients were analysed separately the correlation between concentration and sperm chromatin fragmentation was not significant. For such men, SCSA appears to be a diagnostic variable independent of the semen analysis, providing information about nuclear abnormalities not readily apparent from standard semen analysis alone. Additionally, SCSA data may offer explanations for previous miscarriage, providing closure for some couples contemplating future use of anonymous donor sperm.

Plasma Homocysteine, Fasting Insulin, and Androgen Patterns among Women with Polycystic Ovaries and Infertility

Objective: To measure plasma homocysteine, androgen, and insulin concentrations in women with normal and polycystic‐appearing ovaries in an infertility setting.

Correction of hyperinsulinemia in oligoovulatory women with clomiphene-resistant polycystic ovary syndrome: a review of therapeutic rationale and reproductive outcomes

Polycystic ovary syndrome (PCOS) describes a convergence of chronic multisystem endocrine derangements, including irregular menses, hirsutism, obesity, hyperlipidemia, androgenization, large and cystic-appearing ovaries, insulin resistance and subfertility. Few PCOS patients exhibit all of these features, and often only one sign or symptom is evident. The sequelae of PCOS reach beyond reproductive health, as women affected with PCOS have increased relative risks for myocardial infarction, hypertension, ischemic heart disease, thromboembolic disease and diabetes. Although the adverse health consequences associated with PCOS are substantial, unfortunately most women are not aware of these risks. Indeed, in infertility practice such concerns are secondary as most patients are referred for treatment specifically to achieve a pregnancy. Impairments in insulin metabolism appear central to the physiologic cascade of PCOS, yet clomiphene therapy fails to remedy this defect. Several investigators have described satisfactory reproductive outcomes for PCOS patients treated with oral insulin-lowering agents. In this report, we outline a diagnostic and therapeutic approach for women with PCOS refractory to clomiphene with attention to the underlying insulin imbalance associated with impaired fertility.

Dizygotic twin delivery following in vitro fertilization and transfer of thawed blastocysts cryopreserved at day 6 and 7

OBJECTIVE To report the first conception and delivery following transfer of thawed human blastocysts maintained in extended in vitro culture with cryopreservation at day 6 and 7. DESIGN Case report. SETTING Major urban infertility referral center. PATIENT(S) A 26-year-old woman with pelvic endometriosis and two prior unsuccessful in vitro fertilization/embryo transfer (IVF-ET) attempts. INTERVENTION(S) The patient underwent controlled ovarian hyperstimulation using a combined FSH + hMG protocol, and 24 oocytes were retrieved. MAIN OUTCOME MEASURE(S) Dizygotic twin delivery after IVF and intracytoplasmic sperm injection (ICSI), assisted embryo hatching, and ultrasound-guided transfer of cryopreserved blastocysts. RESULT(S) After three embryos were subjected to assisted hatching, they were transferred fresh on day 3, but no implantation occurred. All nontransferred embryos (n = 11) were observed during extended in vitro culture and three blastocysts were selected for cryopreservation on day 6 and 7; thaw and transfer occurred the following month and a pregnancy was achieved. Dizygotic twins (female/female) were delivered by cesarean in the early third trimester. CONCLUSION(S) Substantial advancements have been made in the field of embryo cryogenics and in vitro fertilization, but controversy remains regarding the value of freezing late-developing human blastocysts. Here we describe the first reported live births with IVF after extended in vitro culture and cryopreservation at day 6 and 7 after fertilization.

Monochorionic-triamniotic triplet pregnancy after intracytoplasmic sperm injection, assisted hatching, and two-embryo transfer : First reported case following IVF

BackgroundWe present a case of monochorionic-triamniotic pregnancy that developed after embryo transfer following in vitro fertilization (IVF).MethodsAfter controlled ovarian hyperstimulation and transvaginal retrieval of 22 metaphase II oocytes, fertilization was accomplished with intracytoplasmic sperm injection (ICSI). Assisted embryo hatching was performed, and two embryos were transferred in utero. One non-transferred blastocyst was cryopreserved.ResultsFourteen days post-transfer, serum hCG level was 423 mIU/ml and subsequent transvaginal ultrasound revealed a single intrauterine gestational sac with three separate amnion compartments. Three distinct foci of cardiac motion were detected and the diagnosis was revised to monochorionic-triamniotic triplet pregnancy. Antenatal management included cerclage placement at 19 weeks gestation and hospital admission at 28 weeks gestation due to mild preeclampsia. Three viable female infants were delivered via cesarean at 30 5/7 weeks gestation.ConclusionsThe incidence of triplet delivery in humans is approximately 1:6400, and such pregnancies are classified as high-risk for reasons described in this report. We also outline an obstetric management strategy designed to optimize outcomes. The roles of IVF, ICSI, assisted embryo hatching and associated laboratory culture conditions on the subsequent development of monozygotic/monochorionic pregnancy remain controversial. As demonstrated here, even when two-embryo transfer is employed after IVF the statistical probability of monozygotic multiple gestation cannot be reduced to zero. We encourage discussion of this possibility during informed consent for the advanced reproductive technologies.

Periovulatory serum human chorionic gonadotropin (hCG) concentrations following subcutaneous and intramuscular nonrecombinant hCG use during ovulation induction: a prospective, randomized trial

OBJECTIVE To describe serum levels of human chorionic gonadotropin (hCG) as a function of hCG injection method (subcutaneous vs. intramuscular) among infertile women undergoing ovulation induction. DESIGN Prospective, randomized clinical trial. SETTING Major urban infertility referral center. PATIENT(S) Women presenting for infertility evaluation and ovulation induction. INTERVENTION(S) Controlled ovarian hyperstimulation was followed by 5,000 IU urinary (nonrecombinant) hCG injection, given intramuscularly (i.m.) or subcutaneously (s.c.). MAIN OUTCOME MEASURE(S) Serum hCG levels measured 24 hours after administration of hCG, and patient tolerability of injected hCG. RESULT(S) There were no statistically significant differences in age or body mass index (BMI) among patients receiving hCG s.c. (n = 13) or i.m. (n = 15). Mean [IQR (25; 75)] serum hCG levels in the s.c. and i.m. groups were 171.7 [27.0; 207.0] and 142.2 [102.5; 157.5] mIU/mL, respectively. No adverse events were registered by any patient receiving hCG by either injection method. In this non-IVF population, two pregnancies were established in each subgroup (4 of 28, or approximately 14% pregnancy rate). CONCLUSION(S) The s.c. administration of 5,000 IU hCG (reconstituted in vol. = 0.5 mL) was well tolerated by all women in this study and was associated with postinjection serum hCG levels similar to those observed after administration of an equivalent i.m. hCG dose. This investigation suggests that clinical use of s.c. hCG is suitable for lean women (e.g., BMI <30) undergoing ovulation induction, but additional data are needed to study the appropriateness of s.c. hCG administration in heavier patients.

Absence of profound hyperinsulinism in polycystic ovary syndrome is associated with subtle elevations in the plasminogen activator inhibitor system

In order to describe potential hypofibrinolytic tendencies in young (< 35 years) polycystic ovary syndrome (PCOS) patients ,we studied plasminogen activator inhibitor (PAI-1) system components in women without laboratory evidence of hyperinsulinism or hyperandrogenism. The study was a prospective ,observational comparison and took place in a major urban infertility referral center. Age ,body mass index, ovulatory status ,selected androgen levels ,fasting insulin and plasma lipids were measured in subjects with PCOS (n = 39) and normal control subjects (n = 20). Women with PCOS had higher mean serum total testosterone and androstenedione levels compared with controls (56.4 versus 40.3 ng/dl ,p = 0.03 ,and 179 versus 133 μg/ml ,p = 0.03 ,respectively). Mean fasting insulin levels were higher among PCOS women (p < 0.01) and were strongly correlated with PAI-1 antigen (Ag) (r = 0.46) ,PAI-1 activity (r = 0.43) ,and tissue plasminogen activator (t-PA) (r = 0.5). Correlations were evident in both PCOS and control subjects. Mean PAI-1 Ag ,PAI-1 activity ,and t-PA levels were significantly elevated (p = 0.003 ,0.001 ,and 0.001 ,respectively) in PCOS. ANOVA was performed to control for insulin effect; a trend toward elevated PAI-1 in PCOS persisted but was no longer statistically significant (p = 0.24). PAI-1 activity elevation remained in PCOS women with mean fasting insulin levels < 10 mIU/ml (p = 0.02) ,yet the difference became less significant when insulin was controlled (p = 0.38). Although these data confirm known associations between insulin and PAI-1 derangements ,this is the first study to quantify discrete PAI-1 elevations that persist in the setting of PCOS even with normal or low ambient insulin levels. Additional prospective studies are needed to determine whether this altered PAI-1 state is associated with a clinically important hypofibrinolytic condition and subsequent poor reproductive outcome.

Laparoscopic Approach to an Uncommon Adnexal Neoplasm Associated with Infertility: Serous Cystadenofibroma of the Fallopian Tube

A rare case of serous cystadenofibroma of the fallopian tube was discovered during evaluation for in vitro fertilization-embryo transfer. Bilateral tubal occlusion was noted on hysterosalpingogram, and a right adnexal cyst, initially thought to be of ovarian origin, was identified by office transvaginal sonography. Laparoscopy revealed a 5.5-cm, fluid-filled mass involving the distal aspect of the right fallopian tube. Both ovaries and uterine exterior appeared grossly normal. The cyst was decompressed and removed intact without incident through a 5-mm laparoscopic cannula. The mass showed histologic features consistent with benign serous cystadenofibroma. The patient had an uncomplicated postoperative convalescence and continued to do well 3 months after surgery.

Comparison of centrifugation- and noncentrifugation-based techniques for recovery of motile human sperm in assisted reproduction

To compare standard density gradient/centrifugation sperm preparation with a novel non-centrifugation-based dual-chamber capillary dish in efficiency for motile human sperm separation, ~3 mL fresh ejaculate specimens was obtained from 21 men (median age = 32 years, range = 26-42 years) undergoing infertility evaluation. For each specimen, half of the sample was processed with a standard 45%/90% density gradient preparation (PureSperm, Nidacon International, Gothenburg, Sweden) followed by semen analysis. The other half was incubated in the Zech glass capillary dish (Astromedtec, Salzburg, Austria) consisting of 2 concentric wells overlaid by a U-ring and coverglass. After ~3 h, a 1-mL sample was taken from the central chamber and analyzed. Percentage motile sperm recovery, absolute (motile) cell number, and path velocities were compared for spermatozoa obtained from both methods. Both techniques reduced overall sperm concentration while enriching specimens with more motile spermatozoa. A trend towards higher % recovery of motile spermatozoa ( p =. 264) was observed with the Zech device, but at a cost of fewer absolute numbers of higher velocity cells ( p =. 004). The Zech device, therefore, localized a very small population of motile sperm without exposure to centrifugation stress, which has been considered potentially harmful to spermatozoa. This technique could theoretically improve efficiency by reducing time required to identify motile cells in in vitro fertilization where intracytoplasmic sperm injection is planned. However, refinements in incubation interval and suspension volumes are needed before this technique can be considered comparable to the density gradient method in recovering sperm for use in intrauterine insemination.

Correlations from gadopentetate dimeglumine-enhanced magnetic resonance imaging after methotrexate chemotherapy for hemorrhagic placenta increta

ObjectiveTo describe pre- and post-methotrexate (MTX) therapy images from pelvic magnetic resonance imaging (MRI) with gadopentetate dimeglumine contrast following chemotherapy for post-partum hemorrhage secondary to placenta increta.Material and methodA 28-year-old Caucasian female presented 4 weeks post-partum complaining of intermittent vaginal bleeding. She underwent dilatation and curettage immediately after vaginal delivery for suspected retained placental tissue but 28 d after delivery, the serum β-hCG persisted at 156 IU/mL. Office transvaginal sonogram (4 mHz B-mode) was performed, followed by pelvic MRI using a 1.5 Tesla instrument after administration of gadolinium-based contrast agent. MTX was administered intramuscularly, and MRI was repeated four weeks later.ResultsWhile transvaginal sonogram suggested retained products of conception confined to the endometrial compartment, an irregular 53 × 34 × 28 mm heterogeneous intrauterine mass was noted on MRI to extend into the anterior myometrium, consistent with placenta increta. Vaginal bleeding diminished following MTX treatment, with complete discontinuation of bleeding achieved by ~20 d post-injection. MRI using identical technique one month later showed complete resolution of the uterine lesion. Serum β-hCG was <5 IU/mL.ConclusionReduction or elimination of risks associated with surgical management of placenta increta is important to preserve uterine function and reproductive potential. For selected hemodynamically stable patients, placenta increta may be treated non-operatively with MTX as described here. A satisfactory response to MTX can be ascertained by serum hCG measurements with pre- and post-treatment pelvic MRI with gadopentetate dimeglumine enhancement, which offers advantages over standard transvaginal sonography.