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Infertility FAQ for Women of Size - Journal Abstracts

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Infertility FAQ for Women of Size
Journal Abstracts

Infertility & Weight

Grodstein F, Goldman MB, Cramer DW, Body mass index and ovulatory infertility., Epidemiology 5: 2, 247-50, Mar, 1994.

Several studies have examined the association between body mass index and infertility. We compared body mass index in 597 women diagnosed with ovulatory infertility at seven infertility clinics in the United States and Canada with 1,695 primiparous controls who recently gave birth. The obese women (body mass index > or = 27) had a relative risk of ovulatory infertility of 3.1 [95% confidence interval (CI) = 2.2-4.4], compared with women of lower body weight (body mass index 20-24.9). We found a small effect in women with a body mass index of 25-26.9 or less than 17 [relative risk (RR) = 1.2, 95% CI = 0.8-1.9; and RR = 1.6, 95% CI = 0.7-3.9, respectively). We conclude that the risk of ovulatory infertility is highest in obese women but is also slightly increased in moderately overweight and underweight women.

Helm P, Munster K, Schmidt L, Recalled menarche in relation to infertility and adult weight and height., Acta Obstet Gynecol Scand 74: 9, 718-22, Oct, 1995

BACKGROUND. Possible relationships between menarche and fertility and fecundity later in life have not been fully clarified.

METHODS. A cross-sectional study was made in a random sample of 3743 women, aged 15-44 years, in the country of Copenhagen; 78% responded. Telephone interviews were made with a sample of the non-respondents.

RESULTS. Associations were observed between early menarche and increased risk of pelvic inflammatory disease (odds ratio 2.4 (1.4-4.1)) and spontaneous abortion (OR 3.1 (1.6-5.7)) later in life. On the other hand, no association was found with irregular bleedings or amenorrhoea; nor was a significant relationship established with fertility or fecundity. Late menarche was associated with underweight (OR 3.1 (1.4-6.9)), and early menarche with excess weight (OR 5.0 (2.4-10.6)). A significant positive correlation (R = 0.17) was found between menarcheal age and final body height.

CONCLUSIONS. Menarche was not associated with fertility or fecundity. Early menarche was associated with pelvic inflammatory disease and spontaneous abortion. Menarche showed relationships with weight and height.

Bilenka B, Ben-Shlomo I, Cozacov C, Gold CH, Zohar S, Fertility, miscarriage and pregnancy after vertical banded gastroplasty operation for morbid obesity., Acta Obstet Gynecol Scand 74: 1, 42-4, Jan, 1995. Address: Department of Obstetrics and Gynecology Rebecca Sieff Government Hospital Safed Israel. Abstract Vertical banded gastroplasty (VBG) is today the most widely performed bariatric operation. The procedures used previously for the same purpose resulted in metabolic derangements and other pathologies during pregnancy. In a retrospective study we compared the reproductive performance of nine women prior to VBG and after it. Of eighteen pregnancies prior to the operation, seven ended with miscarriage, while only one of fourteen pregnancies conceived after the operation was aborted. The rate of spontaneous conception was greatly increased after the operation and there were fewer complications in the course of the pregnancies. From the obstetrician and gynecologist's point of view VBG seems to be a good treatment for morbid obesity.

Kusakari M, Takahashi K, Yoshino K, Kitao M, Relationship between the delayed-reaction type of LH-RH test and obesity in sterile women ovulatory disturbances: a preliminary report., Int J Fertil 35: 1, 14-6 21-2, Jan-Feb, 1990.

We investigated 312 sterile women to look for a possible relationship between obesity and infertility. The LH-RH test was performed on 113 of these women. The obesity index was determined according to the Japanese variation of Broca's index. The results were as follows: (1) Among 312 sterile women, 8.7% were obese and one-fifth of anovulatory patients showed a tendency toward obesity. (2) The pregnancy rate was lower in obese women. (3) The delayed-reaction type in the LH-RH test was observed in 29.2% of total patients; the rate in patients with anovulation (20.4%) was lower than that in those with ovulation (37.3%). (4) The rate of the delayed-reaction type in anovulatory obese patients was 100%. This evidence shows that obesity was related to anovulation and/or infertility, as determined by the delayed-reaction type in the LH-RH test.

Whitaker EM, Obesity and reproduction., Proc Nutr Soc 46: 2, 237-47, Jul, 1987.

Eden JA, Carter GD, Jones J, Alaghband-Zadeh J, Pawson M, Factors influencing the free androgen index in a group of subfertile women with normal ovaries., Ann Clin Biochem 25 ( Pt 4): 350-3, Jul, 1988.

Eighty-five regularly cycling women with normal ovaries at laparoscopy, were studied to determine the factors that influence the free androgen index (FAI). It was found that body mass index (BMI), age of the patient and the phase of the menstrual cycle that the blood was collected can all affect the FAI. It is recommended that where possible, specimens should be collected in the early follicular phase to avoid misinterpretation of the result.


Infertility Drugs & Weight

Franks S, Hamilton-Fairley D, [The role of body weight and metabolic anomalies in ovulation induction], (Le role du poids et des anomalies metaboliques dans l'induction de l'ovulation.), Contracept Fertil Sex 22: 3, 178-9, Mar, 1994.

Obese women with polycystic ovary syndrome require higher doses of gonadotrophin for induction of ovulation than their lean counterparts. They also have a lower rate of ovulation and higher prevalence of miscarriage.

(Gonadatropins = the hormones produced by the pituitary gland that control reproductive function FSH and LH)

Kim JH, Richards CJ, Seibel MM, Proper selection of patients for intermediate-dose pure follicle stimulating hormone., J Reprod Med 39: 1, 1-5, Jan, 1994.

Forty-four polycystic ovary syndrome (PCO) patients were treated for a total of 61 cycles with intermediate-dose pure follicle stimulating hormone (FSH). Patient selection was based on hyperandrogenism, oligoovulation and physical signs. Patients with multiple-factor infertility were excluded from the study. Seventeen conception cycles occurred in 17 patients (pregnancy cycles). The spontaneous abortion rate was 29.4%. Forty cycles did not result in conception (Nonpregnancy cycles, 23 patients). Treatment was discontinued in four patients who had suboptimal response. Sixteen pregnancies (94%) occurred within the first two treatment cycles. Pregnancy and nonpregnancy cycles were compared for characteristics associated with a successful outcome. The data suggest that (1) an intermediate-dose pure FSH protocol is most likely to be successful among more "classic" PCO patients, those with obesity, high body surface area, elevated luteinizing hormone/FSH ratio and higher testosterone; (2) if pregnancy is to occur, it is most likely to within two treatment cycles; and (3) ovarian hyperstimulation is more likely to occur in nonconception cycles.

Shepard MK, Balmaceda JP, Leija CG, Relationship of weight to successful induction of ovulation with clomiphene citrate., Fertil Steril 32: 6, 641-5, Dec, 1979.

Over a 6 1/2-year period, 117 patients who were anovulatory, euthyroid, and estrogen-primed were treated with clomiphene citrate. Graduated doses from 50 mg to 250 mg daily for 5 days were used to induce ovulation. Of 62 patients who completed treatment, 50 ovulated and 12 did not. Several factors, including age, duration of infertility, weight, previous menstrual history, previous pregnancy history, and previous use of oral contraceptives, were investigated to determine conditions which might influence response. Only weight was found to be significantly different between responders and nonresponders. Furthermore, there was a linear relationship between body weight and dose of clomiphene required to induce ovulation. The ovulation rate for those completing therapy was 81% with a pregnancy rate of 76% of the total and 94% of those ovulating. Population homogeneity with anovulation as the major cause of infertility appears to be the most plausible explanation for the high pregnancy rate.


Weight Loss Effects on Infertility

Galletly C, Clark A, Tomlinson L, Blaney F, A group program for obese, infertile women: weight loss and improved psychological health., J Psychosom Obstet Gynaecol 17: 2, 125-8, Jun, 1996.

We report on a group program for obese infertile women. Sixty-four women completed the 24-week program, which included exercise, information about healthy eating and group discussion sessions. Their mean initial weight was 101.9 +/- 18.14 kg. The mean weight loss on completion of the program was 5.2 +/- 5.11 kg (p < 0.0001). There was significant improvement on ratings of self-esteem and depression. Changes to life-style and health which are known to improve fertility may be a useful precursor to invasive, high technology infertility treatment procedures.

Clark AM, Ledger W, Galletly C, Tomlinson L, Blaney F, Wang X, Norman RJ, Weight loss results in significant improvement in pregnancy and ovulation rates in anovulatory obese women., Hum Reprod 10: 10, 2705-12, Oct, 1995.

Obesity can affect ovulation and the chances of pregnancy. In this prospective study, a weight loss programme was assessed to determine whether it could help infertile overweight anovulatory women to establish ovulation and assist in achieving pregnancy, ideally without further medical intervention. The subjects acted as their own historical controls. They underwent a weekly programme of behavioural change in relation to exercise and diet over 6 months; those who did not complete the 6 months were treated as the comparison group. Women in the study group lost an average of 6.3 kg, with 12 of the 13 subjects resuming ovulation and 11 becoming pregnant, five of these spontaneously. Fitness, diet and psychometric measurements all improved. Fasting insulin and testosterone concentrations dropped significantly, while sex hormone binding globulin concentrations rose. None of these changes occurred in the comparison group. Thus, weight loss with a resultant improvement in ovulation, pregnancy outcome, self-esteem and endocrine parameters is the first therapeutic option for women who are infertile and overweight.

Wynn M, Wynn A, Slimming and fertility., Mod Midwife 4: 6, 17-20, Jun, 1994.

Severe reducing diets cause low levels of progesterone, slowing down follicular growth, inhibiting the surge of luteinising hormone (LH) and preventing ovulation. If less severe, slimming may depresses hormone levels by producing too small a corpus luteum and may result in a miscarriage. A reducing diet over a longer period may also affect fertility. Women planning pregnancy should be advised on the regularity as well as the adequacy of meals during the preconception period. A woman's nutritional status may be adequate for fertility but inadequate to produce a baby in the optimum birthweight range. There is a recovery period from amenorrhoea when it is wise not to conceive.


Weight Loss Drugs & Infertility

Galletly C, Clark A, Tomlinson L, Evaluation of dexfenfluramine in a weight loss program for obese infertile women., Int J Eat Disord 19: 2, 209-12, Mar, 1996. OBJECTIVE: To evaluate the usefulness of dexfenfluramine as an adjunct to a group treatment program for obese infertile women.

METHOD: Twenty-one obese infertile women were referred by the Reproductive Medicine Unit. They attended a 24-week group program which included exercise and educational sessions. Dexfenfluramine and placebo were given, each for 12 weeks, in a double-blind crossover design.

RESULTS: Dexfenfluramine treatment was not associated with greater loss of weight. The mean weight loss during dexfenfluramine treatment was 3.21 kg (SD 3.09) and during placebo was 3.31 kg (SD 3.15). Self-esteem, anxiety, and depression ratings all improved significantly over the 24 weeks. DISCUSSION: The group treatment program appeared to be equally effective with or without dexfenfluramine. Previous studies have found dexfenfluramine to be effective in combination with individual treatment, but it has not previously been evaluated as an adjunct to group treatment. It is unclear whether dexfenfluramine may be less effective in combination with group treatment programs, or whether its usefulness is restricted in this particular population of obese patients. No differences were found associated with the order in which active and placebo treatments were given. Patients showed improvement in self-esteem and reduction in depression and anxiety, but dexfenfluramine treatment was not associated with any difference in these measures, compared to placebo.


PCO & Obesity

Balen AH, Conway GS, Kaltsas G, Techatrasak K, Manning PJ, West C, Jacobs HS, Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients., Hum Reprod 10: 8, 2107-11, Aug, 1995.

The criteria for the diagnosis of the polycystic ovary syndrome (PCOS) have still not been agreed universally. A population of 1741 women with PCOS were studied, all of whom had polycystic ovaries seen by ultrasound scan. The frequency distributions of the serum concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone and prolactin and the body mass index, ovarian volume, uterine cross-sectional area and endometrial thickness were determined and compared with the symptoms and signs of PCOS. Obesity was associated with hirsutism and an elevated serum testosterone concentration and was also correlated with increased rates of infertility and cycle disturbance. The rates of infertility and cycle disturbance also increased with serum LH concentrations > 10 IU/l. A rising serum concentration of testosterone [mean and 95th percentiles 2.6 (1.1-4.8) nmol/l] was associated with an increased risk of hirsutism, infertility and cycle disturbance. The ovarian volume was correlated with serum concentrations of testosterone, LH and the body mass index, which was also correlated with the uterine area. This descriptive data from the largest reported series of women with PCOS enables the development of a management-orientated approach to the syndrome. Women who are overweight can expect an improvement in their symptoms if they lose weight. An elevated concentration of LH (> 10 IU/l) is associated with infertility and treatment should be chosen accordingly. If the serum testosterone concentration is > 4.8 nmol/l, other causes of hyperandrogenism should be excluded.

Singh KB, Mahajan DK, Wortsman J, Effect of obesity on the clinical and hormonal characteristics of the polycystic ovary syndrome., J Reprod Med 39: 10, 805-8, Oct, 1994.

The polycystic ovary (PCO) syndrome is frequently associated with obesity. That subset of women reportedly shows a much higher incidence of hirsutism and menstrual irregularities than do nonobese women with PCO syndrome. We evaluated the clinical features and hormonal profiles of 56 women with PCO syndrome and correlated them with the presence or absence of obesity. Thirty-eight (67.8%) of these women were obese (body mass index > or = 25 kg/m2). While presenting with the classic manifestations of PCO, they did not differ significantly from the manifestations of nonobese women with PCO syndrome. Although obese women with PCO had a lower incidence of oligomenorrhea as compared to nonobese women with PCO (57.9% vs. 83.3%, respectively) and amenorrhea was more frequent in the former group (42.1% vs. 16.6%, respectively), these findings are not statistically significant. The incidences of hirsutism and anovulatory infertility in the obese group as compared to the nonobese group were 81.6% vs. 77.8% and 28.9% vs. 27.8%, respectively (not statistically significantly different). The mean (+/- SE) serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), LH/FSH ratios, prolactin and testosterone were not statistically significantly different among the two groups. The present study found that obesity is common in PCO syndrome but that there are no significant differences in the clinical and hormonal characteristics of obese and nonobese women with it. Further studies are warranted to clarify the impact of obesity on clinical, metabolic and hormonal changes in PCO syndrome.

Gjonnaess H, Ovarian electrocautery in the treatment of women with polycystic ovary syndrome (PCOS). Factors affecting the results., Acta Obstet Gynecol Scand 73: 5, 407-12, May, 1994.

During the years 1979-91 252 women with polycystic ovarian syndrome (PCOS) have been treated with ovarian electrocautery through the laparoscope in Aker University Hospital. Ovulation was obtained in 92% of the total series, and pregnancy in 84% of the women with PCOS as the sole cause of their infertility. Additional treatment with clomiphene citrate to the non-responders increased the pregnancy rate to 89%. The response to ovarian electrocautery was influenced by body weight, with an ovulation rae of 96-97% in the slim and moderately obese women decreasing to 70% in the really obese ones. When ovulation was established, the pregnancy rate per se was independent of body weight-when ovulation was established, the pregnancy rates of slim and overweight women with PCOS being 92% and 95%, respectively. In the responders (who ovulated following ovarian electrocautery), the annual rate of cessation of ovulation was 3-4% only. Even after a period of contraceptive use following the ovarian electrocautery, ovulation was resumed and pregnancy obtained within a few months. Therefore, ovarian electrocautery is proposed as the primary treatment in women with PCOS undergoing laparoscopy for any reason, infertility being a present, future or hypothetical problem only. When, on the other hand, infertility is not an issue, PCOS per se constitutes no reason to perform laparoscopy.

Khrennikova OV, Khrennikov VIu, [Carbohydrate metabolic disorder in women with a neuroendocrine syndrome], (Narushenie uglevodnogo obmena u zhenshchin s neiroendokrinnym sindromom.), Akush Ginekol (Mosk) 2, 24-7, , 1994.

A total of 129 women with the neuroendocrine syndrome were examined. A clinico-biochemical heterogeneity of the disease was revealed. One group included patients with the android type of fat deposition, manifest hyperandrogenism, polycystic ovaries, and carbohydrate metabolism disorders (hyperinsulinemia, impaired glucose tolerance, insulin resistance). Severity of carbohydrate metabolism disorders in these patients was unrelated to obesity degree. The other group included patients with the gynoid type of fat deposition, weakly manifest hyperandrogenism signs, and body mass-dependent shifts in carbohydrate metabolism. It is possible that carbohydrate metabolism shifts contribute to the pathogenesis of the clinical picture of the neuroendocrine syndrome.


PCO, Obesity & Miscarriage

Clifford K, Rai R, Watson H, Franks S, Regan L, Does suppressing luteinising hormone secretion reduce the miscarriage rate? Results of a randomised controlled trial., BMJ 312: 7045, 1508-11, Jun 15, 1996.

OBJECTIVE--To determine whether prepregnancy pituitary suppression of luteinising hormone secretion with a luteinising hormone releasing hormone analogue improves the outcome of pregnancy in ovulatory women with a history of recurrent miscarriage, polycystic ovaries, and hypersecretion of luteinising hormone.

DESIGN--Randomised controlled trial. SETTING--Specialist recurrent miscarriage clinic.

SUBJECTS--106 women with a history of three or more consecutive first trimester miscarriages, polycystic ovaries, and hypersecretion of luteinising hormone. INTERVENTIONS--Women were randomised before conception to receive pituitary suppression with a luteinising hormone releasing hormone analogue followed by low dose ovulation induction and luteal phase progesterone (group 1) or were allowed to ovulate spontaneously and then given luteal phase progesterone alone or luteal phase placebo alone (group 2). No drugs were prescribed in pregnancy. MAIN OUTCOME MEASURES--Conception and live birth rates over six cycles.

RESULTS--Conception rates in the pituitary suppression and luteal phase support groups were 80% (40/50 women) and 82% (46/56) respectively (NS). Live birth rates were 65% (26/40) and 76% (35/46) respectively (NS). In the luteal phase support group there was no difference in the outcome of pregnancy between women given progesterone and those given placebo pessaries. Live birth rates from an intention to treat analysis were 52% (26/50 pregnancies) in the group given pituitary suppression and 63% (35/56) in the controls (NS).

CONCLUSIONS--Prepregnancy suppression of high luteinising hormone concentrations in ovulatory women with recurrent miscarriage and hypersecretion of luteinising hormone does not improve the outcome of pregnancy. The outcome of pregnancy without pituitary suppression is excellent.

Tarlatzis BC, Grimbizis G, Pournaropoulos F, Bontis J, Lagos S, Spanos E, Mantalenakis S, The prognostic value of basal luteinizing hormone:follicle-stimulating hormone ratio in the treatment of patients with polycystic ovarian syndrome by assisted reproduction techniques., Hum Reprod 10: 10, 2545-9, Oct, 1995

One of the main endocrinological disturbances in patients with polycystic ovarian syndrome (PCOS) is the increased baseline concentrations of luteinizing hormone (LH) and consequently a high LH:follicle-stimulating hormone (FSH) ratio. The aim of this study was to assess the relationship between the baseline LH:FSH ratio with the stimulation response and the miscarriage risk in PCOS women stimulated for assisted reproduction techniques (ART) with and without gonadotrophin-releasing hormone analogue (GnRHa). Two groups of PCOS patients were analysed retrospectively. Group A (n = 20, 20 cycles) consisted of women stimulated with human menopausal gonadotrophin (HMG), and group B (n = 128, 162 cycles) comprised women stimulated with buserelin-long/HMG. LH and FSH concentrations were measured during the early follicular phase (days 4-6) in a preceding spontaneous or progestin-induced cycle. The following parameters were assessed: number of follicles developed, number of oocytes obtained and percentage of mature oocytes, as well as number of abortions and live births. In group A, the baseline LH:FSH ratio was correlated inversely with the number of follicles developed (P < 0.05), the number of oocytes obtained (P < 0.05) and the percentage of mature oocytes (P < 0.05). In group B, no correlation was found between the LH:FSH ratio and the number of follicles and oocytes, because their numbers were relatively constant irrespective of the baseline LH:FSH ratio, but a significant inverse correlation was noted with the percentage of mature oocytes (P < 0.001). However, a comparison of the slopes of the curve indicated a better correlation between the LH:FSH ratio and the percentage of mature oocytes in group A than in group B (P < 0.05). These findings were also confirmed when patients were subdivided according to the LH:FSH ratio (< 3 or > or = 3). Furthermore, in women who miscarried, the mean LH:FSH ratio was significantly higher than in women having a live birth. In conclusion, in PCOS patients stimulated with HMG, a high basal LH:FSH ratio appears to have an adverse effect on the number of follicles and oocytes, as well as on oocyte maturity. On the other hand, the administration of GnRHa in the long protocol seems to reverse this detrimental effect on follicle and oocyte development. Furthermore, a higher LH:FSH ratio seems to predict a greater possibility for miscarriage, despite the use of GnRHa.

Kurysheva KA, Kolgushkin GA, Georgadze GR, Stol'nikova II, Vorgova TM, [The preclinical diagnosis of threatened abortion and late gestosis in pregnant women with normal body weight and obesity], (Doklinicheskaia diagnostika ugrozy nevynashivaniia beremennosti i pozdnikh gestozov u beremennykh s normal'noi massoi tela i ozhireniem.), Akush Ginekol (Mosk) 2, 17-9, , 1994.

Abstract Measurements of blood serum phosphatidyl inosites in pregnant women with normal body mass and with obesity in whom pregnancy ran normal or pathological course showed that phosphatidyl inositol levels increased 2-3-fold in case of threatened miscarriage and decreased 2-3-fold if symptoms of late gestosis appeared (an abnormal gain in body mass) as compared to their levels in women with an uneventful course of pregnancy. Phosphatidyl inositol levels were higher in obese women that in those with normal body mass, no matter what the pregnancy course was.

Randomised controlled trial of the use of human chorionic gonadotrophin in recurrent miscarriage associated with polycystic ovaries. Author Pearce JM; Hamid RI Address Department of Obstetrics and Gynaecology, St George's Hospital, London. Source Br J Obstet Gynaecol, 1994 Aug, 101:8, 685-

OBJECTIVE: To determine whether the use of human chorionic gonadotrophin (hCG) would reduce the recurrent miscarriage rate in women with polycystic ovarian disease. DESIGN: Double-blind, prospective, randomised controlled trial. SETTING: A pregnancy loss clinic in a London teaching hospital. SUBJECTS: One hundred and ninety-one women with a history of three consecutive spontaneous first trimester miscarriages and polycystic ovary syndrome. INTERVENTION: 10,000 i.u. of hCG or a placebo were given when the leading follicle was > or = 21 mm, then 5000 i.u. of hCG or a placebo were given twice weekly until miscarriage or the tenth week of pregnancy. MAIN OUTCOME MEASURE: Miscarriage rate. RESULTS: Women with polycystic ovaries who received hCG treatment had a lower miscarriage rate (14%) compared with women who received placebo (43%). In women with follicular phase luteinising hormone > 10 iu/l, those who received hCG therapy had a miscarriage rate of 10% compared with a rate of 44% in women who received the placebo. When clomiphene was used for ovulation induction, women treated with hCG had a miscarriage rate of 14% compared with a rate 47% in women who received the placebo. There was no significant benefit from hCG therapy in natural cycles. CONCLUSION: The use of hCG in women with recurrent miscarriage and polycystic ovary syndrome improves the pregnancy outcome.

Homburg R, Levy T, Berkovitz D, et al: Gonadotropin-releasing hormone agonist reduces the miscarriage rate for pregnancies achieved in women with polycystic ovarian syndrome. Fertil Steril 59:527, 1993

Title Gonadotropin-releasing hormone agonist reduces the miscarriage rate for pregnancies achieved in women with polycystic ovarian syndrome. Author Homburg R; Levy T; Berkovitz D; Farchi J; Feldberg D; Ashkenazi J; Ben-Rafael Z Address Department of Obstetrics and Gynecology, Golda Medical Center, Petah Tikva, Israel. Source Fertil Steril, 1993 Mar, 59:3, 527-31 Abstract OBJECTIVE: To compare the effect of treatment with gonadotropin-releasing hormone agonist (GnRH-a) and human menopausal gonadotropins (hMG) with that of gonadotropins only, on the cumulative livebirth rate and miscarriage rate of pregnancies achieved in women with polycystic ovarian syndrome (PCOS). DESIGN: Retrospective analysis of the outcome of 97 pregnancies according to the treatment protocol, with or without GnRH-a. Calculation of miscarriage rate and cumulative livebirth rate by life-table analysis. SETTING: Infertility clinic and in vitro fertilization (IVF) unit. PATIENTS: Women with polycystic ovaries (n = 239) who were clomiphene citrate failures and received either GnRH-a/hMG (n = 110) or gonadotropins only (n = 129) for ovulation induction (n = 138) or superovulation for IVF (n = 101). INTERVENTIONS: For ovulation induction, hMG was given in a step-up, individually adjusted dose scheme. For IVF, three ampules of pure follicle-stimulating hormone were given for 3 days followed by three ampules per day hMG and then individual dose adjustment. Gonadotropin-releasing hormone agonist (Decapeptyl, D-Trp6, microcapsules, 3.75 mg) was given in a single dose 2 weeks before gonadotropin treatment. MAIN OUTCOME MEASURES: The rate of early miscarriages (< 12 weeks) per pregnancies achieved was analyzed, and the cumulative livebirth rate for each treatment group was calculated by life-table analysis. results: miscarriage rates after treatment in ovulation induction with (16.7%) and without gnrh-a (39.4%) and in ivf with (18.2%) and without gnrh-a (38.5%) were almost identical and were therefore analyzed together. of pregnancies achieved with gnrh-a, 17.6% miscarried compared with 39.1% of those achieved with gonadotropins alone. cumulative livebirth rate after four cycles for gnrh-a was 64% compared with 26% for gonadotropins only. conclusions: cotreatment with gnrh-a/hmg for anovulatory women with pcos reduces the miscarriage rate and improves the livebirth rate compared with treatment with gonadotropins alone.

Takeuchi T, Nishii O, Okamura T, Yaginuma T, Kawana T, Free testosterone and abortion in early pregnancy., Int J Gynaecol Obstet 43: 2, 151-6, Nov, 1993.

OBJECTIVES: To investigate the relationship between percentage of free testosterone (% free T) and the abortion rate in early pregnancy.

METHODS: Progesterone (P), estradiol (E2), total T, sex hormone binding globulin (SHBG), and % free T were measured in sera obtained from 60 pregnant women with normal pregnancy (n = 38) and missed abortion (n = 22) at between 4 and 12 weeks' gestation.

RESULTS: P, E2, total T, and SHBG in 22 patients with missed abortion were significantly lower than those in normal group, whereas % free T was significantly higher. There was a significant negative correlation between % free T and SHBG concentration in the normal group, but not in the missed abortion group. All the subjects in whom % free T was 1.30% and higher subsequently miscarried, but no subject with % free T less than 0.70% had a miscarriage.

CONCLUSIONS: The lower the % free T, the lower the rate of subsequent abortion. The value of % free T may be able to predict pregnancy outcome in early pregnancy.

Balen AH, Tan SL, MacDougall J, Jacobs HS, Miscarriage rates following in-vitro fertilization are increased in women with polycystic ovaries and reduced by pituitary desensitization with buserelin., Hum Reprod 8: 6, 959-64, Jun, 1993.

To assess the risk of miscarriage after in-vitro fertilization (IVF) with respect to age, cause of infertility, ovarian morphology and treatment regimen, a retrospective analysis was performed of the first 1060 pregnancies conceived between June 1984 and July 1990 as a result of 7623 IVF cycles. Superovulation induction was achieved with human menopausal gonadotrophin (HMG) and/or purified follicle stimulating hormone (FSH) together with either clomiphene citrate or the gonadotrophin hormone-releasing hormone (GnRH) agonist buserelin, the latter either as a short 'flare' regimen or as a 'long' regimen to induce pituitary desensitization. There were 282 spontaneous abortions (26.6%) and 54 ectopic pregnancies (5.1%). The mean age of women with ongoing pregnancies was 32.2 (SD 3.9) years compared with 33.2 (SD 4.1) years in those who miscarried, which were significantly different (P = 0.008). There was no relation between the miscarriage rate and the indication for IVF. The miscarriage rate was 23.6% in women with normal ovaries compared with 35.8% in those with polycystic ovaries [P = 0.0038, 95% confidence interval (CI) 4.68-23.10%]. There was no difference in the miscarriage rate between treatment with HMG or FSH. Women whose ovaries were normal on ultrasound were just as likely to miscarry if they were treated with clomiphene or with the long buserelin protocol. Those with polycystic ovaries, however, had a significant reduction in the rate of miscarriage when treated with the long buserelin protocol, 20.3% (15/74), compared with clomiphene citrate, 47.2% (51/108) (P = 0.0003, 95% CI 13.82-40.09%).

Tulppala M, Stenman UH, Cacciatore B, Ylikorkala O, Polycystic ovaries and levels of gonadotrophins and androgens in recurrent miscarriage: prospective study in 50 women [see comments], Br J Obstet Gynaecol 100: 4, 348-52, Apr, 1993.

OBJECTIVE: To compare the serum levels of gonadotrophins and androgens, as well as ovarian morphology, in 50 women with a history of recurrent miscarriage and in 20 healthy controls.

DESIGN: Prospective study on women with a history of at least three consecutive miscarriages in Department I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Finland.

RESULTS: The recurrent miscarriage group as a whole exhibited gonadotrophin and androgen levels comparable to those seen in the controls. Ultrasound examination revealed polycystic ovaries (PCO) in 22 patients (44%) and in four control women (20%, P = 0.06) but no differences in the levels of gonadotrophins and androgens emerged between the patients with or without PCO. During follow up, 33 (66%) women with a history of recurrent miscarriage who became pregnant; 16 miscarried again (48.5%), whereas 17 (51.5%) succeeded. The presence of PCO did not predict miscarriage, but the patients who miscarried had higher levels of total testosterone, free testosterone and dehydroepiandrosterone sulphate than RSA women with continuing pregnancies.

CONCLUSIONS: PCO and hyperandrogenism may be associated with repeated miscarriage.

Hamilton-Fairley D, Kiddy D, Watson H: Association of moderate obesity with a poor pregnancy outcome in women with polycystic ovary syndrome treated with low dose gonadotrophin. British journal of obstetrics and gynaecology. 99:128, 1992

OBJECTIVE: To assess the effect of moderate obesity on the outcome of induction of ovulation with low dose gonadotrophin in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective analysis of women with PCOS treated consecutively. An analysis of the impact of obesity on outcome of pregnancy using data from the North West Thames Regional (NWTR) obstetric database was included for comparison. SETTING: Induction of ovulation clinic at the Samaritan Hospital for Women (St. Mary's Hospital Group). SUBJECTS: 100 women with clomiphene-resistant anovulation associated with PCOS. 75 were of normal weight (BMI 19-24.9 kg/m2, lean group) and 25 were moderately overweight (BMI 25-27.9 kg/m2, obese group). INTERVENTIONS: Induction of ovulation using low doses of gonadotrophins with small, stepwise increments in dosage as required. MAIN OUTCOME MEASURES: Rates of ovulation, pregnancy and miscarriage; daily and total doses of gonadotrophin required for induction of ovulation. RESULTS: The proportion of ovulatory cycles was significantly greater in the lean group (77%) compared with the obese group (57%) (chi 2 9.8, P less than 0.001). Obese women required larger doses of gonadotrophin to achieve ovulation (P less than 0.001). The proportion of women who achieved at least one pregnancy was similar in the two groups (39% vs 48%) but miscarriage was more frequent in the obese group (60% vs 27%; P less than 0.05). This difference was independent of the baseline and/or mid-follicular luteinizing hormone (LH) concentration either before or during treatment. Analysis of data from the North West Thames Health Region obstetric database confirmed an increased risk of miscarriage in moderately obese women which was independent of maternal age. CONCLUSIONS: Moderate obesity in women with PCOS, treated with low dose gonadotrophin, is associated with an increased risk of miscarriage. This is reflected in the results of analysis of the effect of obesity on outcome of pregnancy in the general population. It is therefore important to encourage weight reduction in obese women with PCOS before considering therapy to induce ovulation.

Johnson P, Pearce JM, Recurrent spontaneous abortion and polycystic ovarian disease: comparison of two regimens to induce ovulation., BMJ 300: 6718, 154-6, Jan 20, 1990.

OBJECTIVE--To determine whether pituitary suppression before induction of ovulation reduces the rate of spontaneous abortion in women with polycystic ovarian disease and primary recurrent spontaneous abortions.

DESIGN--Closed, randomised, sequential trial. Pairs of women were allocated to each treatment by the toss of a coin. SETTING--Supraregional clinic for women who had had recurrent spontaneous abortions.

SUBJECTS--Forty two women with polycystic ovarian disease and primary recurrent spontaneous abortions. INTERVENTIONS--Ovulation was induced by clomiphene or pituitary suppression with buserelin followed by pure follicle stimulating hormone. MAIN OUTCOME MEASURES--Preference for a particular treatment was noted. A preference occurred when one woman in a pair had a successful pregnancy (defined as one of over 12 weeks' gestation) and one had a spontaneous abortion; the preference was for the treatment resulting in the successful pregnancy.

RESULTS--Spontaneous abortions occurred in 11 of 20 women given clomiphene compared with two of 20 who had pituitary suppression. Eleven preferences were found for buserelin and two for clomiphene. In seven pairs both women had successful pregnancies. One pair was discarded because one of the women did not become pregnant. The ratio of luteinising hormone concentration to follicular diameter was found to be a possible diagnostic indicator of spontaneous abortion.

See Franks.


Pregnancy & Weight

Stevens-Simon C, Metlay LA, McAnarney ER, Maternal weight and weight gain: relationship to placental microstructure and morphometric oxygen diffusion capacity., Am J Perinatol 12: 6, 407-12, Nov 1995.

This study examines the effects of maternal prepregnant weight and gestational weight gain on the size, microstructure, and function of the human placenta. Standard gross, histologic, and histomorphometric techniques were used to examine placentas obtained from the deliveries of 77 poor, black 12- to 30-year-old subjects in relation to maternal prepregnant weight and the rate of maternal weight gain during gestation. The weight, volume, and fetal capillary surface area of the placenta increased significantly in relation to both maternal prepregnant weight and the rate of maternal weight gain during gestation. Prepregnant weight was a more important determinant of placental size and fetal capillary surface area than was the rate of maternal weight gain. The rate of maternal weight gain was a more important determinant of the density of fetal capillary tissues within the placenta and of placental resistance to oxygen diffusion than was prepregnant weight. Both maternal prepregnant weight and the rate of maternal weight gain during gestation relate positively to the size of the placenta, but they have different, potentially complementary effects on placental microstructure and function.

Galtier-Dereure F, Montpeyroux F, Boulot P, Bringer J, Jaffiol C, Weight excess before pregnancy: complications and cost., Int J Obes Relat Metab Disord 19: 7, 443-8, Jul, 1995.

OBJECTIVE: To investigate the incidence of pregnancy complications and the cost of prenatal care in patients with pregravid overweight.

DESIGN: Retrospective study of patients dispatched into four groups: normal weight, moderate overweight, obesity, massive obesity. SETTING: Department of Obstetrics and Gynecology of Montpellier.

SUBJECTS: One hundred and twelve pregnancies among 89 overweight women, compared with 54 healthy normal weight controls. MAIN OUTCOME MEASURES: Incidence of maternal complications, complications of labor, duration of hospitalization.

RESULTS: Hypertension, toxemia, gestational diabetes, insulin treatment, urinary tract infections and macrosomia were positively correlated with maternal pregravid weight excess. Mean duration of hospitalization and overall cost were also strongly related to maternal weight. Cesarean section rate increased only in morbidly obese women. No materno-fetal mortality was observed in our study.

CONCLUSION: Even moderate overweight is a significant risk factor for obstetrical complications and needs a multidisciplinary antenatal management in order to prevent materno-fetal complications.

Isaacs JD, Magann EF, Martin RW, Chauhan SP, Morrison JC, challenges of massive obesity complicating pregnancy., J Perinatol 14: 1, 10-4, Jan-Feb, 1994.

This study examined the effects of massive maternal obesity on medical complications, mode of delivery, postpartum complications, and hospital confinement. In this retrospective case control study, women weighing > 300 pounds delivering from January 1, 1986, to November 1, 1991, were matched for age, race, parity, and height with lean parturient women (mean weight 160 +/- 21 pounds). Among massively obese women there was a greater incidence of chronic hypertension (p < 0.05) and diabetes (p < 0.05) than in the control group. Primary cesarean section was more frequent (p < 0.05), as was the postoperative complication of endometritis when obese patients were compared with lean women (p < 0.05). Cephalopelvic disproportion was the only indication for primary cesarean section, which occurred with greater frequency in the obese group. The postpartum hospital confinement was also significantly longer in the obese study group (p < 0.05). The gestation of a massively obese parturient woman is more frequently complicated by chronic hypertension and diabetes. Abdominal delivery for cephalopelvic disproportion is more likely, and this mode of birth is more often followed by endometritis, which results in longer hospital stays.

Gross T, Sokol RJ, King KC, Obesity in pregnancy: risks outcome., Obstet Gynecol 56: 4, 446-50, Oct, 1980.

Obesity has been associated in the literature with other pregnancy risks such as hypertension and diabetes mellitus, but disagreement persists about the expected course and complications of labor. Also, the effects of obesity on intrauterine growth and gestational duration have not been well defined. This study of 2746 consecutive deliveries used a computer-based uniform perinatal record to compare 300 pregnancy risk and outcome factors for obese and nonobese patients. The 279 obese women (more than 90 kg at some time during the pregnancy) were found to be older and of higher parity than the 2467 who were not obese. Those in the obese group were at increased antepartum risk and had increased frequencies of chronic hypertension, inadequate pregnancy weight gain, twin gestation, and diabetes mellitus. Oxytocin induction and repeat cesarean sections were performed more frequently for the obese patients, with no increase in complications during the current labor. The frequency of labor abnormalities, oxytocin augmentation, and primary cesarean section was similar to that of the comparison group. Examination of infant outcome revealed similar Apgar scores and perinatal mortality in the 2 groups, but fewer low-birth-weight infants (under 2500 g) and more macrosomic babies (over 4000 g) occurred in the obese population. This increase in birth weight was accounted for not only by an increase in the birth weight percentile, but also by a significant lengthening of the period of gestation.


Pregnancy & Weight Gain

Edwards LE, Hellerstedt WL, Alton IR, Story M, Himes JH, Pregnancy complications and birth outcomes in obese and normal-weight women: effects of gestational weight change., Obstet Gynecol 87: 3, 389-94, Mar, 1996

OBJECTIVE: To compare the pregnancy course and outcomes in obese and normal-weight women and their associations with gestational weight change.

METHODS: Multivariate logistic regression described the relation of weight change to pregnancy course and outcomes in a retrospective study of 683 obese and 660 normal-weight women who delivered singleton living neonates.

RESULTS: Compared with normal-weight women, obese women gained an average of 5 kg (11 lb) less during pregnancy and were more likely to lose or gain no weight (11% versus less than 1%). Obese women were significantly more likely to have pregnancy complications, but the incidence of complications was not associated with weight change. Compared with obese women who gained 7-11.5 kg (15-25 lb), obese women who lost or gained no weight were at higher risk for delivery of infants under 3000 g or small for gestational age infants, and those who gained more than 16 kg (35 lb) were at twice the risk for delivery of infants who were 4000 g or heavier.

CONCLUSION: Gestational weight change was not associated with pregnancy complications in obese or normal-weight women. To optimize fetal growth, weight gains of 7-11.5 kg (15-25 lb) for obese women and 11.5-16 kg (25-35 lb) for normal-weight women appear to be appropriate.

Hunt SC, Daines MM, Adams TD, Heath EM, Williams RR, Pregnancy weight retention in morbid obesity., Obes Res 3: 2, 121-30, Mar, 1995

Recent hypotheses suggest that for women who develop morbid obesity, increases in weight associated with pregnancy may represent a significant contribution to their obesity status. The effects of multiple pregnancies on weight gain were studied in 96 morbidly obese women (< 13.6 kg over ideal weight at ages 20-24 or before an earlier first pregnancy and currently > 44.5 kg over ideal weight) and 115 random control women from the Utah population. Self-reported weights for each pregnancy included: prepregnancy, greatest during pregnancy, and 6 weeks following delivery, which were validated against available hospital records. Mean number of pregnancies in each group were similar (4.2 and 4.3), ranging from 1 to 9. Mean current age was 46 and mean weight gain since ages 20-24 was 46.0 kg in the morbidly obese and 14.1 kg in controls. Regression of current weight on total number of pregnancies, adjusting for weight at ages 20-24, showed a 1.3 kg/pregnancy increase in current weight (p = 0.03) with no difference between groups (p = 0.6). Weight gain subsequent to the last pregnancy was not related to the number of pregnancies (p = 0.2). Morbidly obese women gained more weight during pregnancy than controls only for the first pregnancy. Gains were similar for all other pregnancies. Morbidly obese women had smaller weight losses after delivery than the controls, but these differences were not significant. For the first pregnancy, morbidly obese women had a net weight retention that was 4.0 kg greater than the controls at 6 weeks post-partum and an average of 1.6 kg/pregnancy greater retention for the remaining pregnancies. Pregnancy weight gains for each pregnancy subsequent to the first pregnancy were constant. These findings suggest: 1) women who develop morbid obesity have slightly less weight loss after delivery and greater between-pregnancy weight gains than controls; 2) the number of pregnancies does not affect the amount of weight gained after the last pregnancy; and 3) while multiparity may augment weight gain in morbidly obese women, it is probably not a primary factor in the later development of morbid obesity.

Nahum GG, Stanislaw H, Huffaker BJ, Fetal weight gain at term: linear with minimal dependence on maternal obesity., Am J Obstet Gynecol 172: 5, 1387-94, May, 1995.

OBJECTIVE: Our purpose was to determine the shape of the function relating birth weight to gestational age between 37.0 and 42.0 weeks of pregnancy and to determine the effect of maternal obesity on term fetal weight gain in normal pregnancies. STUDY

DESIGN: Birth weights in 326 singleton, term gestations were studied in nondiabetic, nonsmoking white women who had well-dated, uncomplicated pregnancies.

RESULTS: Birth weight was a linear function of gestational age between 37.0 and 42.0 weeks. Mean (+/- SD) fetal weight gain was 12.7 +/- 1.4 gm per day (95% confidence interval 9.9 to 15.5 gm/day). Fetal weight gain was only 0.6 gm per day greater for obese pregnant women than for those of normal weight for height. Male fetuses gained weight 0.5 gm per day faster than females.

CONCLUSION: Fetal weight gain is a linear function of gestational age between 37.0 and 42.0 weeks of pregnancy for normal gestations. The effect of maternal obesity on fetal weight gain at term is small and not clinically significant.

Cogswell ME, Serdula MK, Hungerford DW, Yip R, Gestational weight gain among average-weight and overweight women--what is excessive?, Am J Obstet Gynecol 172: 2 Pt 1, 705-12, Feb, 1995.

OBJECTIVE: Our purpose was to determine the association between increased gestational weight gain and birth weight outcomes for low-income women. STUDY

DESIGN: A total of 53,541 single, live infants delivered from 1990 to 1991 to white, black, and Hispanic women in eight states were evaluated. Multiple logistic regression was used to calculate risk of low and high (> 4500 gm) birth weight, adjusting for selected factors.

RESULTS: The association between gestational weight gain and birth weight varied by prepregnancy body mass index. Risk for low birth weight decreased with increasing weight gain for average-weight women. There was no reduction in risk for low birth weight, however, beyond weight gains of 30 to 34 pounds for overweight women and 15 to 19 pounds for very-overweight women. Risk for high birth weight, however, increased with increasing weight gain in all three groups.

CONCLUSION: Very-overweight women (body mass index > 29 kg/m2) may benefit from an upper guideline of 25 pounds of weight gain to help reduce risk for high birth weight.


Obesity & Risk of Neural Tube Defects

Gary M. Shaw, Ellen M. Velie, Donna Schaffer, Risk of Neural Tube Defect-Affected Pregnancies Among Obese Women Journal of the American Medical Association 1996, vol.275, pp. 10931096, April, 1996.

Objective.--To investigate the risk for neural tube defect (NTD)-affected pregnancies among obese women (ie, women with a body mass index [BMI] >29 kg/m[sup]2[/sup]) compared with women of average prepregnancy weight.

Design.--Population-based case-control study.

Setting.--All hospitals in 55 of 58 counties in California.

Participants.--In-person interviews were conducted with mothers of 538 (88% of eligible) NTD cases (including fetuses and infants electively terminated, stillborn, or born alive) and with mothers of 539 nonmalformed controls (88%)within an average of 5 months from the term delivery date.

Main Outcome Measures.--The risk of an NTD-affected pregnancy among obese women.

Results.--Compared with women whose BMI was less than or equal to 29 kg/m[sup]2[/sup], an increased risk for NTD-affected pregnancy was observed among obese women (odds ratio, 1.9; 95% confidence interval, 1.3 to 2.9). The increased risk was not attributable to maternal nonuse of a vitamin containing folic acid, diabetes, use of diet pills, lower dietary folate intake, or an NTD-pregnancy history. Adjustment for maternal age, education, gravidity, use of vitamins, and use of alcohol did not change the odds ratio. The risk associated with maternal obesity was greater for spina bifida and for other less prevalent NTDs than for anencephaly.

Conclusion.--Because as many as 10% of women may be obese periconceptionally, the observed twofold increasedrisk is relevant to the population burden of NTDs.

(JAMA. 1996;275:1093-1096)

MATERNAL OBESITY DOUBLES RISK FOR BIRTH DEFECTS Folic acid does not appear to protect fetuses of obese women

CHICAGO--Obese women are twice as likely to have children with neural tube defects (NTDs) such as spina bifida, than women who are not significantly overweight, according to two articles in this week's issue of The Journal of the American Medical Association (JAMA).

In one article, Gary M. Shaw, Dr.P.H., from the March of Dimes Birth Defects Foundation, California Birth Defects Monitoring Program, Emeryville, Calif., and colleagues compared 538 women who had a pregnancy involving an NTD fetus with 539 women who had a pregnancy involving a nonmalformed fetus.

The women were considered obese if they had a body mass index (BMI) of more than 29. BMI is weight in kilograms divided by the square of height in meters. For example, a woman who is five-feet-six-inches tall and weighs 185 pounds would have a BMI of 29.9. A woman who is five-feet-three-inches tall and weighs 165 pounds would have a BMI of 29.2. Both would be categorized as obese.

The researchers found that a woman with a BMI of more than 29 had 1.9 times the risk for an NTD-affected pregnancy than a woman with a BMI of 29 or less.

They write: "The increased risk was not attributable to maternal nonuse of a vitamin containing folic acid, diabetes, use of diet pills, lower dietary folate intake, or an NTD-pregnancy history. Adjustment for maternal age, education, gravidity (number of pregnancies), use of vitamins, and use of alcohol did not change the odds ratio. The risk associated with maternal obesity was greater for spina bifida and for other less prevalent NTDs than for anencephaly."

Maternal nutritional factors, such as folic acid intake, have been linked to a reduction in birth defects; however, they do not appear to have a protective effect among obese women.

The authors conclude: "These findings combined with other reports of an increased NTD risk for obese women are provocative, and their follow-up may prove helpful in gaining a better understanding of the complex etiology of NTDs. In addition, because as many as 10 percent of women in the United States are obese periconceptionally and because obesity has been increasing in the U.S., even the modestly increased risks that have been observed are relevant to the population burden of NTDs."

In a separate study in this week's JAMA, Martha M. Werler, Sc.D., and colleagues from Boston University School of Public Health, Brookline, Mass., studied more than 1,200 women in Boston, Philadelphia and southeastern Ontario and found that the risk of NTDs increased with greater prepregnancy weight independent of the effects of folate intake.

They write: "The lack of protection from folate in heavier women must be confirmed in other studies; if it is a true finding, the public health implications would be substantial. A similar pattern of effect modification was observed in a clinical trial of zinc supplementation and pregnancy outcome, where zinc supplements reduced the risk of low birth weight only among nonobese women."

Editorial: Prepregnancy Weight and Pregnancy Outcome

In an accompanying editorial in this week's JAMA, Robert L. Goldenberg, M.D., and Tsunenobu Tamura, M.D., School of Medicine, University of Alabama, Birmingham, write: "It is quite clear that women who are obese have more risk factors than women who are lean or of normal weight, which leads to higher maternal and perinatal morbidity and mortality. It is also possible that obese women have an innate metabolic abnormality or that unmeasured nutritional factors play a role."

They conclude: "Further studies are warranted to investigate the mechanistic relationships among various nutrients, maternal body size, and NTD pregnancies. In the mean time, supplementing the diet of pregnant or soon-to- be pregnant women with both folic acid and zinc as is now commonly practiced seems to be a safe and appropriate intervention."

Editor's Note: The Werler study was supported, in part, by Marion Merrell Dow Inc.

Werler MM, Louik C, Shapiro S, Mitchell AA, Prepregnant weight in relation to risk of neural tube defects [see comments], JAMA 275: 14, 1089-92, Apr 10, 1996.

OBJECTIVE: To examine the relation between prepregnant weight and the risk of neural tube defects (NTDs).

DESIGN: Data were collected from 1988 to 1994 in a case-control surveillance program of birth defects. SETTING: Study subjects were ascertained at tertiary care centers and birth hospitals in the greater metropolitan areas of Boston, Mass, and Philadelphia, Pa, and in southeastern Ontario. PARTICIPANTS: Cases were 604 fetuses or infants with an NTD identified within 6 months of delivery. Controls were 1658 fetuses or infants with other major malformations identified within 6 months of delivery. For 1992 to 1994, there were 93 control infants without major malformations. MAIN OUTCOME MEASURE: Relative risk of NTDs in infants or fetuses for different maternal weights.

RESULTS: Relative to women who weighed 50 to 59 kg, risk of NTDs increased from 1.9 (95% confidence interval [CI], 1.2 to 2.9) for women weighing 80 to 89 kg to 4.0 (95% CI, 1.6 to 9.9) for women weighing 110 kg or more. When women were classified according to daily intake above or below the recommended level of 400 micrograms of folate, approximate threefold increases in risk were estimated for the heaviest weights in both groups. Intakes of 400 micrograms of folate or more reduced risk of NTDs by 40% among women weighing less than 70 kg, but no risk reduction was observed among heavier women.

CONCLUSION: The risk of NTDs increased with increasing prepregnant weight, independent of the effects of folate intake.

Zaadstra BM, Seidell JC, Van Noord PA, te Velde ER, Habbema JD, Vrieswijk B Karbaat J, Fat and female fecundity: prospective study of effect of fat distribution on conception rates [see comments], BMJ 306: 6876, 484-7, Feb 20, 1993.

OBJECTIVES--To study the effect of body fat distribution in women of reproductive age on fecundity.

DESIGN--Prospective cohort study of all women who had entered a donor insemination programme.

SETTING--One fertility clinic serving a large part of the midwest of the Netherlands.

SUBJECTS--Of 542 women attending the clinic for artificial insemination for the first time, 500 women were eligible for study. MAIN OUTCOME MEASURES--Probability of conception per cycle and number of insemination cycles before pregnancy or stopping treatment.

RESULTS--A 0.1 unit increase in waist-hip ratio led to a 30% decrease in probability of conception per cycle (hazard ratio 0.706; 95% confidence interval 0.562 to 0.887) after adjustment for age, fatness, reasons for artificial insemination, cycle length and regularity, smoking, and parity. Increasing age was significantly related to lower fecundity (p < 0.05); very lean and obese women were less likely to conceive (p < 0.10) as were women with subfertile partners (p < 0.10). All other exposure variables were not significantly related to fecundity.

CONCLUSIONS--Increasing waist-hip ratio is negatively associated with the probability of conception per cycle, before and after adjustment for confounding factors. Body fat distribution in women of reproductive age seems to have more impact on fertility than age or obesity.

Farquhar CM, Birdsall M, Manning P, Mitchell JM, France JT, The prevalence of polycystic ovaries on ultrasound scanning in a population of randomly selected women., Aust N Z J Obstet Gynaecol 34: 1, 67-72, Feb, 1994.

Polycystic ovaries (PCO) diagnosed by ultrasound have been commonly reported amongst healthy women. The study aimed to determine the prevalence of PCO in a population of women from the community, and to relate it to clinical and endocrinological data. Twelve hundred women chosen randomly from electoral rolls were invited to take part in the study. Two hundred and fifty five women (21%) who met eligibility criteria greed to participate and 183 women 916%) finally completed the study. Seventy two women did not attend. An ultrasound scan and blood tests were taken on day 5-9 of their menstrual cycles. Data about their menstrual periods and reproductive history was collected. The prevalence of PCO was 21% (39 of 183). No differences existed between women with PCO and normal ovaries with respect to uterine size, body mass index, luteinizing hormone levels, serum hormone binding globulin levels and fertility status. Hirsutism (Ferriman Gallwey score > 7), elevated testosterone levels and irregular menstrual cycles were significantly more frequent amongst women with PCO. Mean ovarian volume was larger in women with PCO irrespective of the use of hormonal contraception. Fifty nine per cent of women with PCO had irregular menstrual cycles or elevated Ferriman Gallwey scores or both. There was no detectable effect of PCO on parity or miscarriage although only 70% of women with PCO had evidence of an adequate ovulation compared to 95% of women with normal ovaries.


Transvaginal Ultrasound

Field NT, Piper JM, Langer O, The effect of maternal obesity on the accuracy of fetal weight estimation., Obstet Gynecol 86: 1, 102-7, Jul, 1995.

OBJECTIVE: To determine if maternal obesity affects the accuracy of either clinical or sonographic fetal weight estimations.

METHODS: In a year-long study, 998 singleton pregnancies of 26-43 weeks' gestation underwent both clinical (Leopold) and sonographic (Shepard and Hadlock) fetal weight estimation within 5 days of delivery (mean 1.1, 95% confidence interval 1.0-1.3). Patients were stratified into four different groups based on increasing maternal body mass index (BMI): underweight (less than 19.8), normal weight (19.8-26.0), overweight (26.1-29.0), and obese (more than 29.0). The various estimations of fetal weight were compared with actual birth weight, and the mean absolute percent error was calculated for each specific method and analyzed among the four BMI groups.

RESULTS: For each method of weight estimation, there was no difference (specifically, no increase) in the magnitude of the absolute percent error with increasing maternal obesity. Regardless of maternal size, almost half of the weight predictions were within 5% of the actual birth weight.

CONCLUSION: Increasing maternal obesity does not alter or decrease the accuracy of either clinical or sonographic fetal weight estimations. Therefore, fetal weight predictions provide equally accurate and valid guidelines for determining management decisions in women, regardless of body size.

Freimanis MG, Jones AF, Transvaginal ultrasonography., Radiol Clin North Am 30: 5, 955-76, Sep, 1992.

Transvaginal ultrasonography has provided new anatomic and pathophysiologic information about the female pelvis. Because of probe proximity to the organ of interest and higher insonating frequency, resolution is dramatically improved. Problems previously encountered during transabdominal scanning, such as obesity, bowel gas, and a retroverted uterus, no longer preclude accurate diagnosis. Patient acceptance is nearly universal. Physiologic information concerning the endometrium and ovarian follicles has improved infertility diagnosis and treatment. Hormonal and vascular Doppler changes can be correlated with cyclic endometrial patterns and follicle size. Oocyte retrieval, management of pre-existing inflammatory disease, and treatment of complications of pregnancy are easier and safer with a transvaginal approach. Uterine malformations, leiomyomas, and cancers are more easily detected in premenopausal and postmenopausal women. The documentation of early intrauterine or ectopic pregnancy has decreased maternal morbidity and mortality. Tube-sparing procedures with preservation of reproductive potential are now more commonly employed due to earlier recognition of unruptured tubal pregnancy. Interventional TVS has led to improved recognition and treatment of pelvic cysts and abscesses and multiple pregnancy. Chorionic villous sampling can be performed more easily without the need for anesthesia, with adequate tissue obtained.


Last revision: April 17, 1998

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