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Chapter 54: Assessing Progesterone During Pregnancy

Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY

Serial progesterone measurement timed to the luteal phase and early pregnancy using CrMS Peak Day-referenced protocols reveals luteal insufficiency and early placental progesterone inadequacy that are associated with miscarriage risk and preterm labor. Progesterone supplementation guided by these standardized assessments has been associated with reduced pregnancy loss in NaProTECHNOLOGY-managed pregnancies, and the chapter details the specific drawing protocols, reference ranges, and supplementation decision thresholds used in clinical practice.

Aromatase Inhibitors in Ovulation Induction. In: Aromatase: Update and New Roles in Reproductive Disease. Carr BR, Bulun SE (Eds)

Mitwally MFM et al., 2004·Sem Reprod Med

Assisted reproductive technology surveillance--United States, 2001

Wright VC et al., 2004·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)

Wright VC(1), Schieve LA, Reynolds MA, Jeng G, Kissin D.

Methodologic and statistical approaches to studying human fertility and environmental exposure

Tingen C et al., 2003·Environ Health Perspect

Although there has been growing concern about the effects of environmental exposures on human fertility, standard epidemiologic study designs may not collect sufficient data to identify subtle effects while properly adjusting for confounding. In particular, results from conventional time to pregnancy studies can be driven by the many sources of bias inherent in these studies. By prospectively collecting detailed records of menstrual bleeding, occurrences of intercourse, and a marker of ovulation day in each menstrual cycle, precise information on exposure effects can be obtained, adjusting for many of the primary sources of bias. This article provides an overview of the different types of study designs, focusing on the data required, the practical advantages and disadvantages of each design, and the statistical methods required to take full advantage of the available data. We conclude that detailed prospective studies allowing inferences on day-specific probabilities of conception should be considered as the gold standard for studying the effects of environmental exposures on fertility.

Prospective pregnancy study designs for assessing reproductive and developmental toxicants

Buck GM et al., 2003·Environ Health Perspect

The determinants of successful human reproduction and development may act as early as periconceptionally, underscoring the need to capture exposures during these critical windows when assessing potential toxicants. To identify such toxicants, couples must be studied longitudinally prior to conception without regard to a couple's ability to ascertain a clinically recognized pregnancy. We examined the utility and feasibility of prospective pregnancy study designs by conducting a systematic review of the literature to summarize relevant information regarding the planning, implementation, and success of previously published prospective pregnancy studies. Information concerning design elements and participation was abstracted from 15 eligible studies (from a total of 20 identified studies) using a standardized form. The primary author of each study was contacted to review our summary of their work and obtain missing information. Our findings confirm the ability to recruit women/couples from diverse populations using a variety of recruitment strategies. Among the studies we reviewed, 4-97% of eligible individuals were successfully contacted, with enrollment rates ranging from 42 to 100%. Length of follow-up varied from 3 to 12 months. A high percentage of women provided urine (57-98%) and blood (86-91%) specimens and most male partners (94-100%) provided semen samples. These data support the feasibility of this design.

ACOG Committee Opinion. Use of progesterone to reduce preterm birth

ACOG, 2003·Obstet Gynecol

Preterm birth affects 12% of all births in the United States. Recent studies support the hypothesis that progesterone supplementation reduces preterm birth in a select group of women (ie, those with a prior spontaneous birth at <37 weeks of gestation). Despite the apparent benefits of progesterone in this high-risk population, the ideal progesterone formulation is unknown. The American College of Obstetricians and Gynecologists Committee on Obstetric Practice believes that further studies are needed to evaluate the use of progesterone in patients with other high-risk obstetric factors, such as multiple gestations, short cervical length, or positive test results for cervicovaginal fetal fibronectin. When progesterone is used, it is important to restrict its use to only women with a documented history of a previous spontaneous birth at less than 37 weeks of gestation because unresolved issues remain, such as optimal route of drug delivery and long-term safety of the drug.

Ovulation induction is not the same as superovulation: the effect of selective estrogen receptor modulators and aromatase inhibitors

Tourgeman DE, 2003·Fertil Steril

Comparison of the effects of letrozole and clomiphene citrate on ovarian follicles, endometrium, and hormone levels in the rat

Kilic-Okman T et al., 2003·Fertil Steril

To compare the effects of letrozole and clomiphene citrate in the rat in terms of number of ovarian follicles; endometrial thickness; and serum levels of E2, FSH, LH, and T. Controlled prospective study. University research laboratory. ANIMAL(S): Thirty sexually mature female Wistar-Albino rats that were 20 weeks of age. INTERVENTION(S): Letrozole, 5 mg/kg of body weight daily (10 rats); clomiphene citrate, 100 microg/kg daily (10 rats); or saline solution, 2 mL/d (10 rats). After 2 days, rats were euthanized and ovariectomized. MAIN OUTCOME MEASURE(S): Number of mature follicles, endometrial thickness, and serum levels of hormones. RESULT(S): Mean levels of FSH, LH, E2, and T; number of mature follicles; and ovary size differed among the groups, whereas the mean endometrial thickness did not differ. CONCLUSION(S): In rats, the effect of letrozole on follicular maturation is similar to that of clomiphene citrate.

Ovulation induction in women with infertility: a new indication for aromatase inhibitors

Bulun SE, 2003·Fertil Steril

The third-generation aromatase inhibitors were initially introduced to treat postmenopausal breast cancer. We now realize that many other potential indications for aromatase inhibitors exist, especially in the field of gynecology. Preliminary data were suggestive that aromatase inhibitors could be used to treat endometriosis and uterine leiomyomata and induce or augment ovulation. Aromatase inhibitors promote ovulation, most likely by increasing endogenous FSH production owing to decreased estrogen biosynthesis in the ovary and extraovarian tissues, including the brain. Aromatase inhibitors differ from the estrogen antagonist clomiphene citrate in that they do not exert a direct unfavorable effect on endometrial growth and development during the menstrual cycle. Healey et al. (1) report important findings on the effects of the addition of an aromatase inhibitor to gonadotropin injections for superovulation. A relatively large number of patients and a control group were studied, and several clinically useful outcomes including pregnancy rates were reported. The addition of letrozole to an ovulation induction regimen using injectable gonadotropins in a mixed population of patients with infertility does not seem to offer any benefits over gonadotropin-only cycles, because the decreased gonadotropin dose (the only apparent benefit) was offset by increased complexity of the treatment. Further randomized clinical trials using a similar design and patient sample may not provide clinically useful data. On the other hand, optimization of this regimen (gonadotropin plus aromatase inhibitor) in poor responders may offer an alternative in this subset of women (2). From the existing literature, it appears that use of an aromatase inhibitor alone to induce or augment ovulation will continue to be an exciting area of research future (3, 4). In particular, the dosing and timing of administration (late luteal versus early follicular) of an aromatase inhibitor for ovulation induction should be optimized. Defining the hormonal profiles of the women who will benefit the most from aromatase inhibition may further increase the success of treatment. In summary, Healey et al. (1) should be congratulated for conducting this interesting work. Carefully designed randomized studies on the use of aromatase inhibitors for ovulation induction or augmentation are warranted.

Classification and pharmacology of progestins

Schindler AE et al., 2003·Maturitas

Besides the natural progestin, progesterone, there are different classes of progestins, such as retroprogesterone (i.e. dydrogesterone), progesterone derivatives (i.e. medrogestone) 17alpha-hydroxyprogesterone derivatives (i.e. chlormadinone acetate, cyproterone acetate, medroxyprogesterone acetate, megestrol acetate), 19-norprogesterone derivatives (i.e. nomegestrol, promegestone, trimegestone, nesterone), 19-nortestosterone derivatives norethisterone (NET), lynestrenol, levonorgestrel, desogestrel, gestodene, norgestimate, dienogest) and spironolactone derivatives (i.e. drospirenone). Some of the synthetic progestins are prodrugs, which need to be metabolized to become active compounds. Besides the progestogenic effect, which is in common for all progestins, there is a wide range of biological effects, which are different for the various progestins and have to be taken into account, when medical treatment is considered.

Letrozole: ovulation or superovulation?

Casper RF, 2003·Fertil Steril

Minimal surgery for the twisted ischaemic adnexa can preserve ovarian function

Oelsner G et al., 2003·Human reproduction (Oxford, England)

Recently detorsion has replaced salpingo-oophorectomy as treatment for the twisted ischaemic adnexa. This paper asssess whether the ovary resumes normal function after preservation by detorsion. The results of detorsion performed between January 1988 and December 2001 were retrospectively analysed. Post-operative complications and subsequent ovarian function ultrasound monitoring of follicular development, adnexal appearance during subsequent surgery, and the outcome of IVF. A total of 102 detorsions were performed; 67 by laparoscopy, 35 by laparotomy. No patient developed thromboembolism. Post-operative fever occurred in 15% of patients after laparoscopy and 29% after laparotomy (P < 0.01). Patients were hospitalized for a mean (+/- SD) of 2.1 +/- 1.2 and 7.4 +/- 1.5 days after laparoscopy and laparotomy respectively (P < 0.001). Ultrasound showed normal follicular development in 93 and 91% of patients after detorsion by laparoscopy and laparotomy respectively. At subsequent surgery, the adnexa appeared normal in nine out of nine patients after laparoscopy and in four out of five patients after laparotomy. Four patients of the laparoscopy group and two patients of the laparotomy group underwent subsequent IVF. In all six patients oocytes retrieved from the previously ischaemic ovary were fertilized. Detorsion with adnexal sparing is the treatment of choice for twisted ischaemic adnexa, and preferably performed by laparoscopy.

Letrozole and gonadotropins: what is the ideal patient protocol?

Healey S et al., 2003·Fertility and Sterility

The Enigma of Chronic Pelvic Pain: Systematically Tracing the Cause

Gambone JC, 2003

Effects of letrozole on superovulation with gonadotropins in women undergoing intrauterine insemination

Healey S et al., 2003·Fertility and sterility

To investigate the effects of letrozole in patients undergoing superovulation with gonadotropins and IUI. Retrospective analysis. Academic teaching hospital. PATIENT(S): Women younger than 40 years of age with patent fallopian tubes and infertility of more than 1 year in duration who were undergoing IUI and gonadotropin therapy. INTERVENTION(S): Gonadotropins alone administered from day 3 or a combination of letrozole, 5 mg/d on day 3 to 7, and gonadotropins starting on day 5 of the menstrual cycle. Ultrasonography was performed before initiation of treatment, on day 9 of menstrual cycle, and as required thereafter until the dominant follicle reached 18 mm in diameter. Ovulation was triggered with 10,000 IU of hCG, and IUI was performed 24 and 48 hours later. MAIN OUTCOME MEASURE(S): Gonadotropin requirements, endometrial thickness, number of follicles, and pregnancy rate. RESULT(S): All 205 IUI treatment cycles conducted from March 2001 to March 2002 were included. Gonadotropins alone were used in 145 cycles and combination therapy was used in 60 cycles. Patients cotreated with letrozole required fewer gonadotropin administrations (median difference, 300 IU [95% confidence interval (CI), 225-375 IU]), developed more follicles larger than 14 mm (median difference, 1 follicle [95% CI, 1-2 follicles), and had a thinner endometrium (median difference, 1 mm [95% CI, 0.4-1.6 mm]). The pregnancy rate did not differ between patients using gonadotropin alone and those using gonadotropin plus letrozole (20.9% vs. 21.6%). CONCLUSION(S): The addition of letrozole to gonadotropins decreases gonadotropin requirements, increases the number of pre-ovulatory follicles and decreases endometrial thickness, without a negative effect on pregnancy rates.

Extraperitoneal endometriosis with catamenial pneumothoraces: a review of the literature

Roberts LM et al., 2003·JSLS

To present a case of recurrent catamenial pneumothorax and diaphragmatic endometriosis that was managed thoracoscopically. A review of the literature is also presented. A-28-year-old woman presented with bloody stools, chronic constipation, and chest pain. A review of systems was positive for monthly chest pain associated with her menses. A preoperative chest x-ray revealed a right pneumothorax. Colonoscopy revealed biopsy proven endometriosis of the sigmoid colon. A pelvic computed tomography scan revealed bilateral complex, cystic and solid adenexal lesions. A right thoracoscopy was performed. A lesion on the right hemidiaphragm was excised and confirmed to be endometriosis. A wedge section of lung tissue containing a bleb was resected and also contained endometriosis. Three months later, the patient underwent laparoscopic excision of her pelvic endometriosis, including a low anterior rectal resection. Five months later, she presented again with right-sided chest pain. A thoracoscopic right total pleurectomy was performed for recurrent pneumothorax. Pullmonary endometriosis may present as chest pain, shortness of breath, or hemoptysis associated with menstrual cycles. This case emphasizes the importance of a careful review of systems in patients with known endometriosis. Management now includes an endoscopic alternative and all of its known benefits.

Ovarian hyperstimulation syndrome

No Authors Listed, 2003·Fertil Steril

Use of clomiphene citrate in women

American Society for Reproductive Medicine, 2003·Fertil Steril

21-hydroxylase-deficient nonclassic adrenal hyperplasia: the great pretender

Moran C et al., 2003·Semin Reprod Med

Polycystic ovary syndrome (PCOS) affects about 4 to 6% of women of reproductive age and accounts for at least 75% of hyperandrogenic patients. PCOS is diagnosed by the presence of oligo-ovulation and hyperandrogenism after the exclusion of related disorders, such as 21-hydroxylase-deficient nonclassic adrenal hyperplasia (NCAH). In turn, NCAH is a homozygous recessive disorder, diagnosed by a corticotropin-stimulated 17-hydroxyprogesterone (17-HP) level greater than10 ng/mL (30.3 nmol/L) and confirmed by genotyping of the CYP21 gene. The prevalence of NCAH is approximately 50 times less than that of PCOS, affecting between 1 and 10% of hyperandrogenic women, depending on ethnicity. However, it is generally difficult to distinguish NCAH from PCOS solely on clinical grounds, as both demonstrate varying degrees of hyperandrogenism and ovulatory dysfunction. Most PCOS patients have insulin resistance, in contrast to those with NCAH. Likewise, polycystic ovaries are observed in up to 40% of NCAH patients. Both disorders have a strong familial component. The only method that allows the separation of NCAH from PCOS patients is the measurement of 17-HP levels. In conclusion, PCOS and NCAH have differences in prevalence and pathophysiology. However, because the disorders have significant clinical and hormonal similarities, the measurement of 17-HP, preferably basally as a screening method, should be incorporated into the evaluation of all hyperandrogenic patients.

Metformin in polycystic ovary syndrome: systematic review and meta-analysis

Lord JM et al., 2003·BMJ

To assess the effectiveness of metformin in improving clinical and biochemical features of polycystic ovary syndrome. Systematic review and meta-analysis. Randomised controlled trials that investigated the effect of metformin compared with either placebo or no treatment, or compared with an ovulation induction agent. 13 trials were included for analysis, including 543 women with polycystic ovary syndrome that was defined by using biochemical or ultrasound evidence. Pregnancy and ovulation rates. Secondary outcomes of clinical and biochemical features of polycystic ovary syndrome. Meta-analysis showed that metformin is effective in achieving ovulation in women with polycystic ovary syndrome, with odds ratios of 3.88 (95% confidence interval 2.25 to 6.69) for metformin compared with placebo and 4.41 (2.37 to 8.22) for metformin and clomifene compared with clomifene alone. An analysis of pregnancy rates shows a significant treatment effect for metformin and clomifene (odds ratio 4.40, 1.96 to 9.85). Metformin has an effect in reducing fasting insulin concentrations, blood pressure, and low density lipoprotein cholesterol. We found no evidence of any effect hip ratio. Metformin was associated with a higher incidence of nausea, vomiting, and other gastrointestinal disturbance. Metformin is an effective treatment for anovulation in women with polycystic ovary syndrome. Its choice as a first line agent seems justified, and there is some evidence of benefit on variables of the metabolic syndrome. No data are available regarding the safety of metformin in long term use in young women and only limited data on its safety in early pregnancy. It should be used as an adjuvant to general lifestyle improvements and not as a replacement for increased exercise and improved diet.

Pregnancy created using egg nucleus of infertile woman

Grady D, 2003·N Y Times Web

Iatrogenic multiple pregnancies. Do they complicate perinatal care?

Nowak E et al., 2003·J Reprod Med

This review addresses questions related to medicosocial concerns surrounding the care of women with multiple births and their infants. Relevant articles and texts on twin and triplet pregnancies were reviewed. Population-based data were selected for inclusion whenever possible. Relevant tables were simplified from original sources. The review clarifies obstetric and perinatal questions in a manner that is helpful to clinicians and their patients.

Excess mortality and morbidity among small-for-gestational-age premature infants: a population-based study

Regev RH et al., 2003·J Pediatr

We examined the effect of intrauterine growth restriction on mortality and morbidity in the Israel cohort of very low birth weight premature infants. The study population included 2764 singleton very low birth weight infants without congenital malformations born from 24 to 31 weeks of gestation during 1995 to 1999. Four hundred six (15%) were born small for gestational age (SGA). The effect of SGA on death, bronchopulmonary dysplasia, and retinopathy of prematurity was assessed using multiple logistic regression analysis. After adjustment for perinatal risk factors, SGA infants had a 4.52-fold risk for death (95% CI, 3.24-6.33), a 3.42-fold risk for bronchopulmonary dysplasia (95% CI, 2.29-5.13), and a 2.06-fold risk for grade 3 to 4 retinopathy of prematurity (95% CI, 1.15-3.66). SGA premature infants had an increased risk for death, and major morbidity among survivors was increased.

Preventing low birth weight: is prenatal care the answer?

Lu MC et al., 2003·J Matern Fetal Neonatal Med

To review the evidence of effectiveness of prenatal care for preventing low birth weight (LBW). We reviewed original research, systematic reviews, meta-analyses and commentaries for evidence of effectiveness of the three core components of prenatal care--risk assessment, health promotion and medical and psychosocial interventions--for preventing preterm birth and intrauterine growth restriction (IUGR). Clinical risk assessment will fail to identify the majority of pregnancies at risk for preterm delivery or IUGR. While biophysical and biochemical modalities appear promising, their cost-effectiveness has not been demonstrated, nor can their routine use be recommended in the absence of effective interventions. Smoking cessation programs appear to be modestly effective. There is insufficient evidence to conclude a benefit for nutrition interventions, work counseling or preterm birth education. Only antenatal corticosteroid therapy has demonstrated a clear benefit in the tertiary prevention of preterm delivery. Interventions for which there is insufficient evidence to conclude a benefit include bed rest, hydration, sedation, cerclage, progesterone supplementation, antibiotic treatment, tocolysis without concomitant use of corticosteroids, thyrotropin-releasing hormone, psychosocial support and home visitation. Additionally, there is a paucity of evidence supporting the effectiveness of prenatal interventions, such as low-dose aspirin, bed rest, maternal hyperoxygenation, plasma volume expansion and antenatal fetal assessment, in preventing IUGR or its associated morbidity and mortality. Neither preterm birth nor IUGR can be effectively prevented by prenatal care in its present form. Preventing LBW will require reconceptualization of prenatal care as part of a longitudinally and contextually integrated strategy to promote optimal development of women's reproductive health not only during pregnancy, but over the life course.

Morphological characterization of different human cervical mucus types using light and scanning electron microscopy

Menárguez M et al., 2003·Human reproduction (Oxford, England)

This study was conducted on human cervical mucus using light microscopy (LM) and scanning electron microscopy (SEM). The objective was the morphological characterization of the different mucus types, with samples taken from the lumen of the cervix and from the different secretory zones of the cervical mucosa. A total of 230 samples from 195 women were spread out on slides and air dried. The phenomenon of 'ferning' was observed and assessed in these samples using both LM and SEM. Further samples from the lumen of the cervix and the different secretory crypts were spread out on cover slips and fixed with glutaraldehyde (2.5%) to be studied by SEM. The results show the presence of four different morphological mucus types, namely L, S, P and G, in both types of sample using dried and fixed techniques. Mucus from the lumen of the cervix appears to be a morphologically heterogeneous entity. It contains different types of secretions, the proportions of which vary throughout the menstrual cycle. The different mucosal types show different types of crystallization, different patterns of ultrastructure (probably related to the arrangement of the glycoprotein network) and are produced in different secretory zones of the crypts in the cervix.

The effects and effectiveness of laparoscopic excision of endometriosis: a prospective study with 2-5 year follow-up

Abbott J, 2003·Human Reproduction

This study investigates the outcomes for women up to 5 years after laparoscopic excision of endometriosis. In this prospective observational cohort study, 254 women with chronic pelvic pain were referred to two units specializing in minimal access surgical management of endometriosis. Of these, 216 women underwent surgical assessment and 176 were confirmed to have endometriosis. Questionnaires and visual analogue scale (VAS) scores for dysmenorrhoea, non-menstrual pelvic pain, dyspareunia and dyschesia as well as quality of life instruments; the EQ-5Dindex and EQ-5Dvas, Short-Form 12 (SF-12) and sexual activity questionnaires were completed pre-operatively. Intra-operative details of revised American Fertility Society (rAFS) stage, site of disease, associated tests, duration of surgery and complications were noted. Follow-up was performed by postal questionnaire and chart review. For women who had further surgery, rAFS stage, site of disease, other procedures and histology were all recorded. Pain scores were all significantly reduced at 2-5 years for dysmenorrhoea (median VAS baseline versus follow-up 2-5 years); 9 versus 3.3 (P < 0.0001), non-menstrual pelvic pain 8 versus 3 (P < 0.0001), dyspareunia 7 versus 0 (P < 0.0001) and dyschesia 7 versus 2 (P < 0.0001). Quality of life was improved for the EQ-5Dindex (P = 0.008 and the EQ-5Qvas (P = 0.03) and for sexual function with pleasure (P = 0.001) and habit (P = 0.012) being improved and discomfort being decreased (P = 0.001). The chance of requiring further surgery as determined by the Kaplan-Meier survival curve was 36%. A rAFS score of >70 was predictive of requiring further surgery (P = 0.03). Of women who had further surgery, endometriosis was found histologically in 68%. Laparoscopic excision of endometriosis significantly reduces pain and improves quality of life for up to 5 years. The probability of requiring further surgery is 36%. Return of pain following laparoscopic excision is not always associated with clinical evidence of recurrence.

Osteoporosis: What a clinician expects to learn from a patient's bone density examination

Brian C Lentle et al., 2003·Radiology

Osteoporosis has lately become recognized as an important disease on two accounts. On one hand, demographic change has resulted in a greatly increased and increasing burden of morbidity and mortality due to osteoporotic fracturing. On the other hand, lifestyle changes and preventive measures have become recognized as important factors in prevention of both osteoporosis and osteoporotic fractures, while several effective drug treatments have recently become available to treat osteoporosis by increasing bone density and reducing fracture incidence. Because bone density is, with age, the best predictor of fracture risk, its measurement has become central to the care of those potentially at risk. When a clinician refers a person for a bone density examination, the clinician should be concerned less with an "imaging diagnosis" than with the requirement that the laboratory has procedures in place for rigorous quality assurance and precision measurements, as well as for education of the staff involved. Implementation of these measures and an understanding of their clinical relevance in diagnosis and follow-up, as well as communication with clinicians in this context, are more important than any diagnostic insight that might be provided by "interpreting" a bone density study.

Time to pregnancy: results of the German prospective study and impact on the management of infertility

Gnoth C et al., 2003·Hum Reprod

The likelihood of spontaneous conception in subsequent cycles is important for a balanced management of infertility. Previous studies on time to pregnancy are mostly retrospective and biased because of exclusion of truly infertile couples. The study aim was to present a non-parametric estimation of cumulative probabilities of conception (CPC) in natural family planning (NFP) users illustrating an ideal of human fertility potential. A total of 346 women was observed who used NFP methods to conceive from their first cycle onwards. The couples practising NFP make optimal use of their fertility potential by timed intercourse. The CPC were estimated for the total group and for couples who finally conceived by calculating Kaplan-Meier survival rates. A total of 310 pregnancies occurred among the 346 women; the remaining 36 women (10.4%) did not conceive. Estimated CPC for the total group (n = 340 women) at one, three, six and 12 cycle(s) were 38, 68, 81 and 92% respectively. For those who finally conceived (truly fertile couples, n = 304 women), the respective pregnancy rates were 42, 75, 88 and 98% respectively. Although the numbers of couples in both groups were similar, the impact of age on time to conception, as judged by the Wilcoxon test, was less in the truly fertile than in the total group. Most couples conceive within six cycles with timed intercourse. Thereafter, every second couple is probably either subfertile or infertile. CPC decline with age because heterogeneity in fecundity increases. In the subgroup of truly fertile couples, an age-dependent decline in CPC is statistically less obvious because of high homogeneity, even with advancing age.

Uterine and ovarian function in endometriosis

Garrido N et al., 2003·Semin Reprod Med

Although numerous studies have attempted to elucidate the implication of endometriosis for infertility, this matter still remains unexplained. Diverse clinical approaches based on assisted reproduction techniques have produced conflicting results on this issue. Nevertheless, impairment of implantation and pregnancy rates seems to affect women who suffer from endometriosis. Whether this effect is due to alteration of the oocyte/embryo or the endometrium still remains to be elucidated, although actual data allude to deficiencies in both. Infertility due to poor quality embryos derived from impaired oocytes obtained from malfunctioning ovaries have been described by some groups. Endometrial defects have been argued by others. Adding more confusion to this topic, the influence of peritoneal fluid in women with endometriosis and/or mixed causes also needs to be considered. The aim of this review is to describe the current situation in the endometriosis-related infertility literature.

Future directions in endometriosis research

Hastings JM et al., 2003·Semin Reprod Med

Endometriosis is an estrogen-dependent condition that affects 5 million American women; however, its etiology is not fully understood. The development of the baboon model of endometriosis provides an extremely powerful tool to investigate the development and progression of endometriosis from the early invasive phase to the advanced established disease. The inflammatory reaction that occurs in the peritoneal cavity at the site of endometriotic lesions does not clear the refluxed endometrial fragments. Moreover, this reaction appears to promote the survival of the tissue and the development of the disease. Exploration of the interactions between peritoneal macrophages and cytotoxic T cells and endometrial cells will determine whether their ability to scavenge and induce apoptosis is altered. Determining the mechanism(s) that induces the expression of estrogen and its receptor (ERbeta) is crucial to our understanding of the progression of the disease. The effects of ERbeta activation in endometriotic lesions should be investigated. It is important to determine the effects of estrogen on the function of the immune cells, either directly or indirectly. Finally, determining the effect of events at sites of ectopic endometrium on the eutopic endometrium may elucidate the mechanism(s) of infertility associated with endometriosis.

Endometriosis and subfertility: is the relationship resolved?

D'Hooghe TM et al., 2003·Semin Reprod Med

There are many arguments to support the hypothesis that there is a causal relationship between the presence of endometriosis and subfertility. These arguments are reviewed (1) an increased prevalence of endometriosis in subfertile women compared with women of proven fertility; (2) a reduced monthly fecundity rate (MFR) in baboons with mild to severe (spontaneous or induced) endometriosis compared with those with minimal endometriosis or a normal pelvis; (3) a trend toward a reduced MFR in infertile women with minimal to mild endometriosis compared with women with unexplained infertility; (4) a a negative correlation between the r-AFS stage of endometriosis and the monthly fecundity rate and crude pregnancy rate; (5) a reduced monthly fecundity rate and cumulative pregnancy rate after donor sperm insemination in women with minimal-mild endometriosis compared with those with a normal pelvis; (6) a reduced MFR after husband sperm insemination in women with minimal to mild endometriosis compared with those with a normal pelvis; (7) a reduced implantation rate per embryo after IVF in women with moderate to severe endometriosis compared with women with a normal pelvis; and (8) an increased monthly fecundity rate and cumulative pregnancy rate after surgical removal of minimal to mild endometriosis.

The association between osteoporotic fractures and health-related quality of life as measured by the Health Utilities Index in the Canadian Multicentre Osteoporosis Study (CaMos)

J D Adachi et al., 2003·Osteoporos Int

Osteoporotic fractures can be a major cause of morbidity. It is important to determine the impact of fractures on health-related quality of life (HRQL). A total of 3,394 women and 1,122 men 50 years of age and older, who were recruited for the Canadian Multicentre Osteoporosis Study (CaMos), participated in this cross-sectional study. Minimal trauma fractures of the hip, pelvis, spine, lower body (included upper and lower leg, knee, ankle, and foot), upper body (included arm, elbow, sternum, shoulder, and clavicle), wrist and hand (included forearm, hand, and finger), and ribs were studied. Participants with subclinical vertebral deformities were also examined. The Health Utilities Index Mark II and III Systems were used to assess HRQL. Past osteoporotic fractures varied in prevalence from 1.2% (pelvis) to 27.8% (lower body) in women and 0.3% (pelvis) to 29.3% (wrist) in men. Multivariate linear regression analyses [parameter estimates and corresponding 95% confidence intervals (CI)] indicated that minimal trauma fractures were negatively associated with HRQL and that this relationship depends on fracture type and gender. The multi-attribute scores for the Mark II system were negatively related to hip (-0.05; 95% CI: -0.09, -0.01), lower body (-0.02; 95% CI: -0.03, -0.000), and subclinical vertebral fractures (-0.02; 95% CI: -0.03, -0.00) for women. The multi-attribute scores for the Mark III system were negatively related to hip (-0.09; 95% CI: -0.14, -0.03) and rib fractures (-0.06; 95% CI: -0.11, -0.00) for women, and rib fractures (-0.06; 95% CI: -0.12, -0.00) for men. In conclusion, this study demonstrates a negative association between osteoporotic fractures and quality of life in both women and men.

Mortality and neurologic, mental, and psychomotor development at 2 years in infants born less than 27 weeks' gestation: the Leiden follow-up project on prematurity

Rijken M et al., 2003·Pediatrics

To determine the outcome of infants with a gestational age (GA) <27 weeks, born in the mid-1990s. Regional, prospective study; part of the Leiden Follow-Up Project on Prematurity. Three health regions in The Netherlands. A total of 266 live born infants (1996/1997) with GA <32 weeks; 46 infants were <27 weeks. Neurologic examination (according to Hempel) and assessment of mental and psychomotor development using the Bayley Scales of Infant Development I, at the corrected age of 2 years. Mortality was 35% (16 of 46) <27 weeks, compared with 6% (14 of 220) in infants with GA 27 to 32 weeks; withdrawal of treatment in 60% and 43%, respectively. Below 27 weeks mortality was higher after extra-uterine transport and pregnancy induction. Neonatal morbidity was higher in infants <27 weeks compared with infants 27 to 32 weeks. Below 27 weeks postnatal use of dexamethasone and being hospitalized at term were associated with abnormal neurologic outcome; there was a higher incidence in (mild) mental developmental delay compared with the older infants. Adverse outcome (dead or abnormal neurologic, psychomotor, or mental development) in infants 23 to 24, 25, 26, and 27 to 32 weeks GA was, respectively, 92% (11 of 12), 64% (7 of 11), 35% (8 of 23), and 18% (40 of 220). Mortality and neonatal morbidity were higher in infants with GA <27 weeks compared with infants born between 27 and 32 weeks. The high adverse outcome of infants <25 weeks suggests that one should carefully weigh whether or not to aggressively resuscitate and treat these extremely premature infants.

Decreased maximal aerobic capacity with use of a triphasic oral contraceptive in highly active women: a randomised controlled trial

C M Lebrun et al., 2003·Br J Sports Med

Oral contraceptives are commonly used by women athletes. However, their effect on athletic performance is unclear. To examine the effects of a moderate dose, triphasic oral contraceptive on measures of athletic performance in highly trained women athletes. This is a double blind, placebo controlled trial in 14 women with ovulatory menstrual cycles and maximal aerobic capacity (VO(2)MAX) >/==" BORDER="0">50 ml/kg/min. Four measures of athletic VO(2)MAX, anaerobic capacity (anaerobic speed test), aerobic endurance (time to fatigue at 90% of VO(2)MAX), and isokinetic strength (Cybex II dynamometer). Height, weight, and six skinfold measurements were also recorded. All these observational tests were completed during both the follicular and mid-luteal phases of an ovulatory menstrual cycle. Cycle phases were confirmed by assaying plasma oestradiol and progesterone. Participants were subsequently randomly assigned to either a tricyclic oral contraceptive or placebo and retested in identical fashion (oral contraceptive phase). Absolute and relative changes in VO(2)MAX from follicular to oral contraceptive phase decreased in the oral contraceptive group by 4.7%, whereas the placebo group showed a slight increase (+1.5%) over the same time period. Two of the women taking oral contraceptive had decreases of 4 and 9 ml/kg/min. In contrast, most women in the placebo group improved or maintained VO(2)MAX. There was also a significant increase in the sum of skinfolds in women taking oral contraceptive compared with those taking placebo (p<0.01). There were no significant changes in other physiological variables (maximum ventilation, heart rate, respiratory exchange ratio, packed cell volume) or measures of performance (anaerobic speed test, aerobic endurance, isokinetic strength) as a function of oral contraceptive treatment. The decrease in VO(2)MAX that occurs when oral contraceptive is taken may influence elite sporting performance in some women. Further studies are required to determine the mechanisms of this change.

Endometrial abnormalities in infertile women

Kurabayashi T et al., 2003·J Reprod Med

To analyze retrospectively the frequency, long-term prognosis and pregnancy rate in infertile women diagnosed with endometrial hyperplasia or carcinoma by endometrial biopsy. From 1989 to 2000, endometrial biopsies were performed on 2,573 patients to investigate the cause of infertility. The main outcome measures were frequency, long-term prognosis and pregnancy rate for patients with each type of endometrial abnormality. Twenty-four patients (0.93%) were diagnosed with an endometrial abnormality. Of them, 10 were diagnosed with simple hyperplasia, 7 with complex hyperplasia, 3 with complex hyperplasia with atypia and 4 with endometrial carcinoma. All 4 patients (0.16%) with endometrial carcinoma were infertile as a result of complications arising from polycystic ovary syndrome. Two of them underwent hysterectomies. High-dose medroxyprogesterone acetate therapy combined with assisted reproductive technology resulted in pregnancy in 1 of the 2 patients with endometrial carcinoma. Of infertile women, 0.93% have endometrial abnormalities, and those with polycystic ovary syndrome have a high risk of endometrial carcinoma. Assisted reproductive technology combined with high-dose medroxyprogesterone acetate may be effective means of overcoming infertility, allowing women with endometrial carcinoma to readily achieve pregnancy.

Couples' views of the effects of natural family planning on marital dynamics

Vande Vusse L et al., 2003·J Nurs Scholarsh

Natural Family Planning (NFP) requires periodic abstinence and partner cooperation to prevent pregnancy. The aim of this study was to learn about the effects of modern NFP methods on marital relationships. Descriptive survey. Questionnaires were mailed to 1,400 randomly selected couples known to use NFP and residing in the United States of America; 334 couples (24%) responded. Content analysis was used to identify meanings and themes. Numeric analyses were used to determine frequencies. Nearly two-thirds of the qualitative comments were positive. Four themes were identified relationship enhancements, knowledge improvements, spirituality enrichments, and method successes. Three negative strained sexual interactions, worsened relationships, and method problems. Although about one-fourth of the comments indicated that NFP presented challenges, the majority (74%) found it beneficial, often resulting in stronger bonds, better communication, and improved knowledge. NFP had more positive than negative effects and its use warrants further consideration.

Estrogen in the adult male reproductive tract: a review

Hess RA, 2003·Reproductive biology and endocrinology : RB&E

Testosterone and estrogen are no longer considered male only and female only hormones. Both hormones are important in both sexes. It was known as early as the 1930's that developmental exposure to a high dose of estrogen causes malformation of the male reproductive tract, but the early formative years of reproductive biology as a discipline did not recognize the importance of estrogen in regulating the normal function of the adult male reproductive tract. In the adult testis, estrogen is synthesized by Leydig cells and the germ cells, producing a relatively high concentration in rete testis fluid. Estrogen receptors are present in the testis, efferent ductules and epididymis of most species. However, estrogen receptor-alpha is reported absent in the testis of a few species, including man. Estrogen receptors are abundant in the efferent ductule epithelium, where their primary function is to regulate the expression of proteins involved in fluid reabsorption. Disruption of the alpha-receptor, either in the knockout (alphaERKO) or by treatment with a pure antiestrogen, results in dilution of cauda epididymal sperm, disruption of sperm morphology, inhibition of sodium transport and subsequent water reabsorption, increased secretion of Cl-, and eventual decreased fertility. In addition to this primary regulation of luminal fluid and ion transport, estrogen is also responsible for maintaining a differentiated epithelial morphology. Thus, we conclude that estrogen or its alpha-receptor is an absolute necessity for fertility in the male.

Cyclicity of breast tenderness and night-time vasomotor symptoms in mid-life women: information collected using the Daily Perimenopause Diary

Hale GE et al., 2003·Climacteric

The purpose was to explore cyclicity of breast tenderness and vasomotor symptoms in menstruating mid-life women using the Daily Perimenopause Diary. Untreated mid-life women from a convenience sample completed the Daily Perimenopause Diary for clinical (n = 14) or research (n = 10) assessments. Breast tenderness, sleep disturbance and day and night vasomotor intensity were rated on a 0-4 scale with vasomotor number as a count. Daily oral temperature data were analyzed using the Quantitative Basal Temperature algorithm to assess ovulation and estimate luteal phase length. Analysis of variance tested cyclicity using the mean of three 3-day windows (during flow, at mid-cycle and premenstrually). Ninety-eight complete flow-to-flow diaries (from 24 women, mean age 47 years, cycle length 27 +/- 6.4 (standard deviation) days) were available, with quantitative temperature data for 60 cycles in 16 women. Of assessed cycles, 90% were ovulatory; 25% had luteal phases < 10 days. Breast tenderness was maximal in the premenstrual window overall (p < 0.0001) and in the ovulatory subset. Night sweats were maximal premenstrually (p = 0.0035) except in anovulatory cycles. Daytime flushes were not cyclic (p = 0.1333) except in ovulatory cycles (p = 0.031). Daily Perimenopause Diaries from mid-life women show premenstrual increases in breast tenderness and night sweats.

Uncertainty in estimating the day of ovulation causes overestimation of the role of ovulation disturbance on the effectiveness of the Yuzpe method of emergency contraception

Mikolajczyk R et al., 2003·Contraception

Reproductive medicine and violation of the "free exercise" clause of the United States Constitution

Hilgers TW, 2003·Linacre Q

Over the years of my involvement in obstetrics and gynecology, and reproductive medicine and surgery I have had the opportunity to see, first hand, how the religious liberties of individual physicians, medical students, nurses, patients, etc., have been violated by the contemporary trends in reproductive medicine. Since the advent of oral contraceptives, the practice of obstetrics and gynecology as it relates to procreative medicine has dramatically changed. Contraception, sterilization, abortion and in vitro fertilization are the foundation upon which reproductive medicine decision making is made. These decisions are often made with a "steam roller effect" which is completely devoid of any consent from those who are impacted by the implementation of those decisions. It has been an interesting series of events to watch over these years as the profession has become less and less diagnostically attuned and more and more "band aid" oriented. The birth control pill is used for the treatment of almost every gynecologic malady known, even though it cures none of them. Family physicians, internists, pediatricians and others tend to follow the same approach as their OB-GYN colleagues. With in vitro fertilization, instead of finding out what the underlying cause of one's infertility or reproductive problem might be, there is a "jumping over" of the underlying causes (the diseases) and a pursuit directly to a solution which first of all is very expensive, second, is not very effective and third, is considered to be highly immoral and unethical by many people in our society.

Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate

Meis PJ et al., 2003·N Engl J Med

Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery. We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle. Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation (incidence, 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group; relative risk, 0.66 [95 percent confidence interval, 0.54 to 0.81]), delivery at less than 35 weeks of gestation (incidence, 20.6 percent vs. 30.7 percent; relative risk, 0.67 [95 percent confidence interval, 0.48 to 0.93]), and delivery at less than 32 weeks of gestation (11.4 percent vs. 19.6 percent; relative risk, 0.58 [95 percent confidence interval, 0.37 to 0.91]). Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen. Weekly injections of 17P resulted in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants.

Progesterone and preterm delivery--deja vu all over again

Greene MF, 2003·N Engl J Med

It has become almost a platitude to lament the complexity and intractability of the problem of preterm delivery, the poor predictive value of screening tests for its occurrence, its resistance to attempted interventions, and its increasing rate.1 Preterm delivery is more common among blacks, the poor, the unmarried, cigarette smokers, underweight women, women with multiple gestations, women with uterine anomalies, women with a history of previous preterm delivery, and women without prenatal care. Although the perinatal mortality rate due to prematurity has decreased dramatically during the past three decades, this reduction has resulted from improvements in perinatal and pediatric care . . .

Hormonal monitoring of ovarian activity using the Ovarian Monitor, part I. Validation of home and laboratory results obtained during ovulatory cycles by comparison with radioimmunoassay

Blackwell LF et al., 2003·Steroids

A study was conducted to determine the accuracy and reliability of the Home Ovarian Monitor for measuring estrone glucuronide (E1G) and pregnanediol glucuronide (PdG) during ovulatory cycles as a means of monitoring ovarian activity. Approximately 60 ovulating women in three centres collected timed specimens of urine (3h or more) for a total of six cycles each. The women measured the E1G and PdG excretion per 24h in their urine specimens using the Monitor. A local laboratory using the Monitor also measured the excretion. Urine specimens from 18 to 19 cycles were sent frozen to the WHO Reference Laboratory in London where they were analysed for E1G and PdG by the Monitor and by radioimmunoassay (RIA). The correlation coefficients between the Monitor and radioimmunoassay results obtained in London were better than 0.84 in 80% of the cycles. A urine bias caused the Monitor E1G results to be higher than those obtained by radioimmunoassay but the daily patterns were the same. In 50% of the cycles, this bias caused a delay of up to 3 days in identifying the beginning of the E1G rise compared with radioimmunoassay. Timing of the preovulatory E1G peak and the postovulatory PdG rise agreed within the experimental errors of the two systems. The study confirmed that women using the Monitor at home obtained results that were as accurate as those obtained by laboratory procedures. Careful supervision was required to maintain laboratory levels of quality control and interpretation of results.

Relation of intra-abdominal fat distribution to metabolic disorders in nonobese patients with polycystic ovary syndrome

Yildirim B et al., 2003·Fertil Steril

To investigate the relation between intra-abdominal fat distribution and metabolic disorders in nonobese patients with the polycystic ovary syndrome (PCOS). Prospective case-control study. University-based hospital. PATIENT(S): Thirty nonobese patients with PCOS and 30 lean women with regular menstrual cycles (controls). All participants had a body mass index < 25kg/m(2). Subcutaneous and intra-abdominal visceral and preperitoneal fat thicknesses were assessed by ultrasonography. Glucose tolerance and insulin sensitivity were evaluated by standard 75-g oral glucose tolerance test and area-under-the-curve analysis. Serum hormones and lipid profile were measured. RESULT(S): The mean preperitoneal and visceral fat thicknesses were significantly greater in nonobese patients with PCOS. Subcutaneous fat mass was similar between the PCOS and control groups. Nonobese patients with PCOS had glucose intolerance, hyperinsulinemia, and dyslipidemia, manifested by high serum levels of triglyceride, total cholesterol, and high-density lipoprotein (HDL) levels and low serum low-density lipoprotein (LDL) levels. No correlation existed between subcutaneous fat thickness and the metabolic variables in nonobese patients with PCOS. However, serum triglyceride levels correlated with visceral fat and preperitoneal fat thickness. The mean HDL level correlated negatively with visceral fat and preperitoneal fat thickness. The area under the curve for insulin and mean fasting insulin levels correlated positively with visceral fat thickness. In multiple regression analysis, visceral fat thickness contributed significantly to high serum triglyceride and fasting insulin levels. CONCLUSION(S): Intra-abdominal preperitoneal and visceral fat accumulation may contribute to the development of glucose and lipid metabolism disorders in nonobese patients with PCOS.

Do assisted reproductive technologies cause adverse fetal outcomes?

Kovalevsky G et al., 2003·Fertil Steril

Treatment for infertility using assisted reproductive technologies (ART) is highly successful and has been used to help a steadily growing number of couples worldwide. In 1999, in the United States, more than 86,000 treatment cycles were performed resulting in the birth of more than 30,000 babies. Despite this widespread application, few follow-up studies of children conceived through ART have been performed, and more rigorous investigation of this important issue has clearly been needed. In recent months, three studies linking ART with several complications have been published in high profile and widely Schieve et al. (1) reported that singletons conceived using ART were at an increased risk for low birth weight, whereas Hansen et al. (2) suggested an increased risk of major birth defects. Finally, Stromberg et al. (3) concluded that children conceived through IVF have an increased risk of neurological problems, especially cerebral palsy. The importance of these studies is obvious as they provide clues of possible risks associated with ART. However, they are all retrospective analyses of data collected through registries and therefore are vulnerable to biases inherent to such study design. We must be careful not to overinterpret the data by concluding that the use of ART, whether from gamete or embryo manipulation or use of medications, is the direct cause of the complications—the observed associations may simply be explained by one or more confounders, such as an underlying infertility-related condition in the treated women. This short communication is an attempt to place these three articles in proper perspective for the clinician and to provide the impetus for conducting further studies to determine the true nature of the described associations. At the outset, it should be stated that a major weakness of all three studies is the lack of proper controls. If the aim of a study is to determine whether a cause and effect relationship exists between the process of IVF and a specific outcome (i.e., low birth weight, major birth defects, neurological problems), the appropriate control population is that of babies born to infertile women achieving pregnancies by methods other than IVF. None of the three studies specifically included such a control population.

Vulvar mucus observations and the probability of pregnancy

Stanford JB et al., 2003·Obstet Gynecol

To assess the day-specific and cycle-specific probabilities of conception leading to clinical pregnancy, in relation to the timing of intercourse and vulvar mucus observations. This was a retrospective cohort study of women beginning use of the Creighton Model Fertility Care System in Missouri, Nebraska, Kansas, and California. Data were abstracted from Creighton Model Fertility Care System records, including women's daily standardized vulvar observations of cervical mucus discharge, days of intercourse, and clinically evident pregnancy (conception). Established statistical models were used to estimate day-specific probabilities of conception. Data were analyzed from 1681 cycles with 81 conceptions from 309 normally fertile couples (initially seeking to avoid pregnancy) and from 373 cycles with 30 conceptions from 117 subfertile couples (who were initially trying to achieve pregnancy). The highest probability of pregnancy occurred on the peak day of vulvar mucus observation (.38 for normally fertile couples and.14 for subfertile couples). The probability of pregnancy was greater than.05 for normally fertile couples from 3 days before to 2 days after the peak, and for subfertile couples from 1 day before to 1 day after the peak. The cycle-specific probability of conception correlated with the quality of mucus discharge in normally fertile couples but not in subfertile couples. Standardized vulvar observations of vaginal mucus discharge identify the days with the greatest likelihood of conception from intercourse in normal fertility and subfertility and provide an indicator of the overall potential for conception in a given menstrual cycle in normal fertility.

Subcutaneous versus intramuscular administration of human chorionic gonadotropin during an in vitro fertilization cycle

Stelling JR et al., 2003·Fertil Steril

To confirm that hCG levels in follicular fluid and serum would be comparable between i.m. and s.c. administration of purified hCG. In a prospective study, serum and follicular fluid levels of hCG after an i.m. or s.c. injection of 10,000 IU of hCG were evaluated 36 hours after injection, that is, at the time of oocyte retrieval. This study was carried out in a university-affiliated IVF program. PATIENT(S): Forty women undergoing oocyte retrieval were entered into the study at the time of egg retrieval, that is, 36 hours after hCG administration. INTERVENTION(S): S.c. or i.m. injection of hCG. MAIN OUTCOME MEASURE(S): Serum and follicular fluid concentrations of hCG were evaluated 36 hours after injection at the time of oocyte retrieval. RESULT(S): There was a significantly higher serum hCG level in the s.c. group (348.6 +/- 98 IU/L) vs. the i.m. group (259.0 +/- 115 IU/L) and a significantly higher follicular fluid hCG level in the s.c. vs. the i.m. group (233.5 +/- 85 vs. 143.4 +/- 134 IU/L). CONCLUSION(S): After purified hCG administration via the s.c. route, both serum and follicular fluid levels are greater compared with the i.m. route.

Success of laparoscopic ovarian wedge resection is related to obesity, lipid profile, and insulin levels

Duleba AJ et al., 2003·Fertil Steril

To evaluate the effects of laparoscopic ovarian wedge resection on hormonal and metabolic parameters of polycystic ovary syndrome (PCOS) and to compare profiles of women who achieved pregnancy with those who did not. Prospective study. University hospital. PATIENT(S): Thirty-three women with PCOS. INTERVENTION(S): Laparoscopic ovarian wedge resection using harmonic scalpel. MAIN OUTCOME MEASURE(S): Pregnancy; levels of testosterone, DHEAS, gonadotropins, sex hormone-binding globulin (SHBG), and glucose and insulin during 2-hour glucose tolerance test; lipid profile; body mass index; and waist-to-hip ratio. RESULT(S): Twenty-two women (67%) achieved clinical pregnancy within the mean of 4.9 months after surgery. Baseline parameters of women who became pregnant differed those who became pregnant were less obese, had lower levels of total cholesterol, low-density lipoprotein, and triglycerides; higher levels of SHBG; lower levels of fasting insulin; lower insulin area under the curve; and higher insulin sensitivity index. Subjects not pregnant by 12 weeks after surgery underwent repeat endocrine and metabolic evaluations. In these women, wedge resection was followed by declines in testosterone, LH, and insulin sensitivity index. Wedge resection had no significant effect on SHBG, DHEAS, or lipid profile. CONCLUSION(S): Laparoscopic wedge resections are associated with the highest pregnancy rates among less obese subjects with favorable lipid profiles and lower insulin. In this study, the postoperative decline of serum testosterone and LH is not attributable to improvement of insulin sensitivity.

Metformin has direct effects on human ovarian steroidogenesis

Mansfield R et al., 2003·Fertil Steril

To investigate the possibility of direct effects of metformin on ovarian steroidogenesis. Cultured ovarian cells. Academic research environment. PATIENT(S): Women undergoing bilateral salpingoophorectomy for benign gynecological disease. MAIN OUTCOME MEASURE(S): Estradiol and P were measured in granulosa cell (GC) conditioned medium and androstenedione (A) and P in theca conditioned medium. RESULT(S): The effect of addition of metformin alone to GCs was variable, but significant inhibition of both P and E2 was seen (range 0%-30%). Metformin dose-dependently inhibited gonadotrophin and insulin-stimulated P and E2 production (range 25%-50%). In theca, metformin inhibited A production (0%-40%) with no effect on P. In the presence of insulin, A was inhibited dose-dependently and P increased by a similar magnitude. CONCLUSION(S): These results demonstrate a direct effect of metformin on ovarian steroidogenesis. The inhibitory effects on androgen production in particular would be beneficial in polycystic ovary syndrome (PCOS).

Use of recombinant human chorionic gonadotropin in ovulation induction

Ludwig M et al., 2003·Fertil Steril

To review the use of hCG and to describe the clinical benefit of recombinant hCG (r-hCG) based on the published results of prospective, randomized studies. Review of published articles. Tertiary infertility care center.None.None. Oocyte number and quality, luteal phase progesterone, pregnancy and OHSS rate, and local tolerability. The published data consistently show that single doses of 250 microg r-hCG and 5,000 IU urinary (u)-hCG produce similar clinical outcomes when used in infertility treatment cycles for timed intercourse, IUI, and IVF in terms of the number of oocytes retrieved, number of mature oocytes harvested, and fertilization and pregnancy rates attained. Single doses of 10,000 IU u-hCG also gave results comparable to single doses of 250 microg r-hCG. P levels in the midluteal phase were significantly higher with the use of r-hCG compared with u-hCG, and local injection site adverse effects were significantly less frequent, demonstrating the higher purity of the recombinant product. A single 500-microg dose of r-hCG led to a higher rate of ovarian hyperstimulation syndrome compared with a 250-microg dose, with no significant improvement in pregnancy rates.A single dose of 250 microg r-hCG was at least as effective as single doses of 5,000 or 10,000 IU u-hCG but offered the advantages associated with local injection site adverse effects were significantly less frequent with r-hCG than with u-hCG.