Daniel Grow

Human sperm devoid of PLC, zeta 1 fail to induce Ca(2+) release and are unable to initiate the first step of embryo development.

Egg activation, which is the first step in the initiation of embryo development, involves both completion of meiosis and progression into mitotic cycles. In mammals, the fertilizing sperm delivers the activating signal, which consists of oscillations in free cytosolic Ca(2+) concentration ([Ca(2+)](i)). Intracytoplasmic sperm injection (ICSI) is a technique that in vitro fertilization clinics use to treat a myriad of male factor infertility cases. Importantly, some patients who repeatedly fail ICSI also fail to induce egg activation and are, therefore, sterile. Here, we have found that sperm from patients who repeatedly failed ICSI were unable to induce [Ca(2+)](i) oscillations in mouse eggs. We have also shown that PLC, zeta 1 (PLCZ1), the sperm protein thought to induce [Ca(2+)](i) oscillations, was localized to the equatorial region of wild-type sperm heads but was undetectable in sperm from patients who had failed ICSI. The absence of PLCZ1 in these patients was further confirmed by Western blot, although genomic sequencing failed to reveal conclusive PLCZ1 mutations. Using mouse eggs, we reproduced the failure of sperm from these patients to induce egg activation and rescued it by injection of mouse Plcz1 mRNA. Together, our results indicate that the inability of human sperm to initiate [Ca(2+)](i) oscillations leads to failure of egg activation and sterility and that abnormal PLCZ1 expression underlies this functional defect.

Sperm morphology as diagnosed by strict criteria: probing the impact of teratozoospermia on fertilization rate and pregnancy outcome in a large in vitro fertilization population

OBJECTIVE To investigate the predictive value of sperm morphology assessed by strict criteria on IVF outcome. DESIGN Retrospective analysis of all IVF cycles (January 1987 to December 1992). MAIN OUTCOME MEASURES All patients were assigned to one of three groups based on sperm morphology: P-pattern (< 4% normal forms), G-pattern (4% to 14% normal forms), and N-pattern (> 14% normal forms). Morphology pattern was related to other semen characteristics and IVF outcome. RESULTS Despite corrective measures at oocyte insemination, the fertilization rate was significantly different among the three morphology groups, P < G < N. N-pattern sperm produced a mean fertilization rate over 85% regardless of low motility or concentration. In a cohort study, P-pattern cycles produced a lower implantation rate and lower ongoing pregnancy rate, independent of the lower fertilization rate. CONCLUSIONS Strict morphology is an excellent biomarker of sperm fertilizing capacity, independent of motility and concentration. P-pattern sperm may denote a poorer prognosis for establishing a pregnancy, even after a satisfactory fertilization rate is achieved.

Value of sperm morphology assessed by strict criteria for prediction of the outcome of artificial (intrauterine) insemination

Summary The purpose of this study was to investigate the relationship between sperm parameters and the outcome of artifical (intrauterine) insemination (IUI). One hundred and twenty‐six patients undergoing 395 consecutive IUI cycles in a 1‐year period in our institution were studied. In all cases, controlled ovarian stimulation and hCG‐timed IUI were performed, followed by progesterone supplementation of the luteal phase. In 86 patients, (243 cycles) the husbands sperm was utilized, whereas in 40 couples (152 cycles), donor sperm was used due to severe male factor infertility. Among the sperm parameters of the original ejaculate, % normal morphology (assessed by strict criteria) was the most significant predictor of pregnancy (stepwise regression analysis, P = 0.003). Using logistic regression, morphology was the best predictor of pregnancy (r = 0.12); linearity of movement significantly enhanced the predictive value of morphology alone (r = 0.17, P = 0.004). Overall, the pregnancy rates were significantly higher (P = 0.01) in cases with ≥ 14% normal morphology (15% per cycle) compared to cases with < 14% normal morphology (7% per cycle). This threshold level for morphology is in agreement with previously published IVF results. These results underscore the significance of sperm morphology assessed by strict criteria as a predictor of pregnancy outcome in the IUI setting.

The use of methotrexate and arterial embolization to avoid surgery in a case of cervical pregnancy

OBJECTIVE To describe the management of a case of cervical ectopic pregnancy (EP) DESIGN: Case report. SETTING University-affiliated teaching hospital. PATIENT(S) A 26-year-old woman, gravida 4, para 0-1-2-0 with the diagnosis of a cervical EP. INTERVENTION(S) Systemic methotrexate (MTX) and arterial embolization. RESULT(S) A cervical EP was diagnosed by ultrasonography. The patient was treated with systemic MTX. Vaginal bleeding began 4 days later and was treated with arterial embolization, thus eliminating the need for surgical intervention. The pregnancy resolved and the patient has resumed normal menstruation and again is attempting pregnancy. CONCLUSION(S) Arterial embolization can be used to avoid surgical intervention in cases of cervical EP in which hemorrhage occurs after treatment with chemotherapy.

Role of hypoestrogenism or sex steroid antagonism in adhesion formation after myometrial surgery in primates

OBJECTIVE To determine the contribution of estrogen in the development of pelvic adhesions during myometrial surgery. DESIGN A randomized, prospective study in the nonhuman primate. SETTING A primate colony, Department of Obstetrics and Gynecology, Eastern Virginia Medical School. INTERVENTIONS All primates were assigned prospectively to one of three treatment groups: [1] GnRH analogue (GnRH-a), [2] mifepristone, or [3] vehicle control. After 3 months of treatment, a standard uterine fundal hysterotomy, for full thickness endometrial biopsy, was performed at the time of exploratory laparotomy, with subsequent scoring of utero-omental adhesions to the hysterotomy site at a future staging procedure based upon adhesion area, vascularity, and tenacity. Serum was drawn on the day of surgery for E2 determination. Endometrial height, from the surface interface between the endometrium and myometrium, was used as a bioassay of estrogen activity. RESULTS The hypoestrogenic (GnRH-a) group and the mifepristone group had significantly fewer utero-omental adhesions compared with the normally cycling control monkeys as measured by a lower adhesion score. Similarly, the endometrial thickness was significantly reduced in the GnRH-a and mifepristone groups (one-third) compared with the cycling controls, demonstrating the effects of either hypoestrogenism or noncompetitive estrogen antagonism. Serum E2 on the day of surgery was predictive of the postoperative adhesion score by both a regression analysis and analysis of covariance. CONCLUSIONS The actions of E2 seem to have a dramatic effect on the formation of pelvic adhesions after myometrial surgery.

Antral follicle count in clinical practice: analyzing clinical relevance

OBJECTIVE To determine the clinical relevance of obtaining antral follicle counts (AFC) before ovarian stimulation in an IVF program. DESIGN Retrospective cohort study. SETTING An IVF program in a large academic teaching hospital. PATIENT(S) A total of 1,049 stimulated IVF cycles in 734 subjects between September 2003 and December 2007 selected from our programs database. INTERVENTION(S) Basal antral follicles (AFCs) (3 mm-10 mm) were counted via ultrasound scan on cycle day 3 in luteal leuprolide acetate stimulations, or after at least 2 weeks of oral contraceptives in microdose leuprolide acetate stimulations. Patients were grouped according to basal AFC, and outcome parameters compared for AFC groups within each stimulation protocol. MAIN OUTCOME MEASURE(S) Oocytes retrieved, ovarian response, implantation rate, cancellations, pregnancy, pregnancy loss, and live births per cycle start. RESULT(S) Antral follicle count grouping is predictive of threefold change in ovarian response to gonadotropins and oocytes retrieved. Low AFC did predict a higher cancellation rate. Antral follicle count did not predict implantation rate, pregnancy rate, or live birth rate per cycle start. CONCLUSION(S) Antral follicle count may be helpful in determining stimulation protocol, as it is the most reliable determinant of oocytes retrieved per starting FSH dose. Antral follicle count predicts ovarian response, not embryo quality or pregnancy.

Metabolism of endogenous and exogenous reproductive hormones

Estradiol and progesterone are produced in abundance by the ovary of the reproductive-age female (and by the placenta in pregnancy). Serum levels of both hormones are very low in the postmenopause, and indistinguishable from women who have undergone castration. Postmenopausal women have higher levels of aromatase in skin and adipose and convert androstenedione to estrone more effectively than younger women. Estradiol is well absorbed orally, but undergoes extensive first-pass effect resulting in production of the less potent metabolites estrone and estrone sulfate. Ethinyl estradiol is well absorbed, potent, and has more pronounced effects in the production of important hepatic proteins. Progesterone is absorbed orally only if ingested in a micronized form, has a relatively short serum half-life, and is metabolized to products with little biologic activity. The synthetic progestogens are abundant in number; potent in effect; and well absorbed orally, vaginally, and transdermally. New formulations of estrogens and progestogens and new delivery systems promise to provide gynecologists and patients with a long list of potential solutions to contraceptive needs and alternatives for hormone replacement therapies.

NEW CONTRACEPTIVE METHODS

As the number of abortion procedures performed each year reaches nearly 1 million, the incentive to decrease the incidence of unwanted pregnancy in the United States is high. Better education regarding womens health issues and enhanced contraceptive development are necessary to impact this long-standing problem. Several new contraceptive products are likely to become available in years to come to increase the number of choices that women and their health care providers have for pregnancy prevention. These products include long-acting implants, the levonorgestrel intrauterine device, patches, and the vaginal ring. This article surveys the near future of male and female contraception.

Complications of laparoscopy. Strategies for prevention and cure.

With a detailed knowledge of pelvic anatomy, familiarity with the many laparoscopic instruments, and attention to the details of good technique, many of the complications of laparoscopy described in this article can be avoided. The information presented complements that in the other articles in this issue and briefly summarizes many salient lessons already published in other excellent texts. The focus is on the most common laparoscopic complications, namely, those associated with insufflation and trocar insertion, such as vascular injury and bowel perforation. Other complications that may arise during adhesiolysis, removal of and bleeding from an ectopic pregnancy, and specimen removal from the abdomen are also discussed.

Gonadotropin-releasing hormone agonist pretreatment did not decrease postoperative adhesion formation after abdominal myomectomy in a randomized control trial

OBJECTIVE To determine if 3 months of preoperative gonadotropin-releasing hormone agonist (GnRH-a) treatment decreases postoperative uterine adhesions after open abdominal surgery for the removal of uterine fibroids. DESIGN Prospective, randomized, clinical study. SETTING A tertiary care medical center. PATIENT(S) Women of reproductive age with symptomatic uterine fibroids not amenable to hysteroscopic removal. INTERVENTION(S) Twenty patients underwent an initial abdominal myomectomy followed by a second-look laparoscopy for evaluating uterine adhesions after random allocation to groups receiving either GnRH analog or placebo for 3 months before the initial surgery. MAIN OUTCOME MEASURE(S) Adhesion formation between treatment groups and by incision number and aggregate length. RESULT(S) Presurgical GnRH-a treatment did not decrease adhesion formation compared with placebo. For every additional centimeter of incision length, the total adhesion area over the uterine serosal surface increased by 0.55 cm(2). The number of myomas removed and the number of incisions were positively correlated with total adhesion area. CONCLUSION(S) Preoperative treatment with GnRH-a for 3 months before open abdominal myomectomy did not decrease postoperative uterine adhesions. Following the standards of good surgical technique, adhesions are minimized with fewer and smaller incisions.