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Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery.We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks).Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGESPrior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization.The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

Pregnancy after conization is associated with a high risk of preterm delivery. However, because risk factors for preterm delivery after conization remain unknown, we conducted a multicenter observational study to investigate risk factors associated with preterm delivery. We selected patients who had previously undergone conization and reviewed medical records from 18 hospitals in cooperation with Keio University School of Medicine between January 2013 and December 2019. Women were classified as nulliparous and primiparous, and a multiple logistic regression analysis was performed to evaluate the relative contributions of the various maternal risk factors for preterm delivery (i.e. delivery before 37 gestational weeks). Among 409 pregnant women after conization, 68 women delivered preterm (17%). The incidence of nulliparity (p = .014) was higher and a history of preterm delivery (p = .0010) was more common in the preterm delivery group than in the term delivery group. Furthermore, the proportion of women diagnosed with adenocarcinoma in situ (AIS) and cervical cancer in the preterm delivery group was higher than that in the term delivery group (p = .0099 and .0004, respectively). In multiple regression models in nulliparous women, cervical cancer or AIS (Odds ratio [OR]: 4.16, 95% CI: 1.26–13.68, p = .019) and a short cervix in the second trimester (OR: 13.41, 95% CI: 3.88–46.42, p < .0001) increased the risk of preterm delivery. Furthermore, a history of preterm delivery (OR: 7.35, 95% CI: 1.55–34.86, p = .012), cervical cancer or AIS (OR: 5.07, 95% CI: 1.24–20.73, p = .024), and a short cervix in the second trimester (OR: 4.29, 95% CI: 1.11–16.62, p = .035) increased the risk of preterm delivery in the multiple regression models in primiparous women. Pregnant women who previously underwent conization are at risk for preterm delivery. The histological type of AIS and cervical cancer was evaluated as a risk factor for preterm delivery. KEY MESSAGESPrior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization.The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group. Prior preterm delivery, presence of a short cervix, and cervical cancer or AIS were predictors of preterm delivery after conization. The depth of conization in cervical cancer or AIS group was significantly larger than that in the CIN group.

In order to determine whether treatment of endocrinologically normal women with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG) led to alternations in follicular fluid inhibin activity and steroids, both inhibin activity and steroid levels were measured in follicular fluid of 10 follicles of 9 women treated with hMG/hCG and in follicular fluid of 15 preovulatory follicles of 15 untreated women. The women were given 150 IU hMG daily from day 3 until the serum estrogen levels were > 300 pg/ml, at which time hMG was discontinued and 10,000 IU hCG was given 50 hours later. Follicular fluid was aspirated from all visible follicles 36 hours after hCG. Women treated with hMG/hCG had multiple (two to five) follicles containing 1.5 to 4.5 ml of follicular fluid and a mature oocyte and elevated serum estrogen (400 to 800 pg/ml) on the day after hCG treatment. At the time of follicular fluid recovery, there was more inhibin activity (204 ± 14 U/10 ml) in the hMG/hCG-stimulated follicles than in unstimulated follicles of a control group of women (65 ± 14, mean ± standard error, P

The ovaries of 25 human infants from 18 to 200 days of age were obtained at autopsy, and their follicular fluid was subjected to measurement of inhibin activity, estrogen, progesterone, androstenedione, and testosterone. Significant inhibin activity was present in all samples of follicular fluid (charcoal-treated) (138 +/- 19 U/10 microliter follicular fluid; 10,545 +/- 2758 U/ovary). There was a tendency for greater inhibin activity, follicular volume, and estrogen in infants from 18 to 59 days than in older infants. There was a significant positive correlation between follicular fluid volume, estrogen, and androstenedione, compared with follicular fluid inhibin content per ovary. It is possible that elevated serum follicle-stimulating hormone and luteinizing hormone observed early in life stimulates follicle growth, inhibin, and estrogen production. As a result of elevated inhibin and estrogen, the gonadotropins may be inhibited, which may cause a decline in follicular activity after 4 to 6 months.

Ovarian tissue obtained from three human infants (60, 120, and 210 days of age) was separated into cell types and cultured. Granulosa cells from two of three subjects were viable and grew in culture. The cells had the potential to secrete low levels of progesterone and responded to luteinizing hormone and follicle-stimulating hormone added in culture with greatly enhanced ability to secrete progesterone. Granulosa cells could also secrete inhibin activity in culture and responded to luteinizing hormone and follicle-stimulating hormone with enhanced inhibin secretion. The granulosa cells also had the potential to secrete estrogen in the presence of testosterone. Serum levels of gonadotropin in the human infant are elevated for a period between 1 and 4 months; yet only follicular growth, not luteinization, occurs. It can be concluded that infant human granulosa cells, like adult human granulosa cells, have the potential of responding in vitro to gonadotropin.

To examine inhibin-F activity (FSH-suppressing activity) in human follicular fluid of polycystic ovary (PCO) patients, 13 follicles from 5 documented PCO patients and an additional 31 follicles from normal women in the follicular phase of the menstrual cycle were sampled, and inhibin-F activity was measured in rat anterior pituitary cell cultures. Inhibin-F activity was measured in follicular fluid after stripping steroids from the fluids using treatment with dextran and activated charcoal. Estrogen, progesterone, and delta 4-androstenedione in the follicular fluid were also determined by RIA. Estrogen and progesterone levels in follicular fluid from PCO follicles 3.9 +/- 0.34 mm in diameter were comparable with those in follicular fluid obtained from viable follicles (which had a delta 4-androstenedione to estrogen ratio of 10 or less) from normal women. delta 4-Androstenedione levels in PCO follicles were higher (P less than 0.01) than those in viable and atretic follicles of normal women. Inhibin-F levels in PCO follicles were comparable to those in viable follicles, but significantly greater (P less than 0.01) than levels in atretic follicles of normal women. If inhibin-F levels in both atretic and viable follicles of normal women were pooled, the levels were less (P less than 0.05) compared to the level in PCO follicular fluid. As an additional control, follicular fluid was collected from 90 follicles of normal women throughout the menstrual cycle, and follicular size was determined as well as inhibin-F and steroid content. Small follicles less than 8 mm; (comparable in size to the PCO follicles examined) obtained at each stage represented 79%, 24%, 0%, and 94% of the total follicles obtained in the early to midfollicular, late follicular, preovulatory, and luteal phases of the cycle, respectively. Inhibin-F activity in the fluids of these follicles was less than that in PCO follicular fluid. The average inhibin content of all of the small normal follicles was 197 +/- 34 U/10 microliter, which was significantly less (P less than 0.05) than the level in PCO follicles (332 +/- 13 U/10 microliters). These data represent the first observation of inhibin-F activity in PCO follicular fluid and suggest the possibility of involvement of inhibin-F in bringing about low or normal basal levels of FSH in the presence of elevated basal LH levels often observed in PCO patients.

Ovarian vein serum from 3 subjects during the late follicular phase of the menstrual cycle had detectable inhibin activity, whereas ovarian vein serum of 12 other subjects during the early follicular phase and luteal phase had no detectable inhibin activity in a rat anterior pituitary cell culture assay. Subjects having detectable inhibin activity (102 +/- 47 U/100 microliters) had 1257 +/- 582 U/100 microliters inhibin activity in FF, whereas subjects having no detectable inhibin activity had FF levels of 711 +/- 203 U/100 microliters of inhibin activity. Estrogen levels of FF and ovarian vein serum of the group having detectable inhibin activity in ovarian vein serum were 282 +/- 239 ng/ml and 4.8 +/- 1.77 ng/ml, respectively. The estrogen content of FF and ovarian vein blood of the group having nondetectable inhibin activity in ovarian vein blood was 127 +/0 45 ng/ml and 3.03 +/- 0.6 ng/ml, respectively.

Repetitious administration of charcoal-stripped porcine follicular fluid (pFF) to four intact cycling females and six long term castrate rhesus monkeys was associated with a gradual onset of resistence to the FSH-suppressing effects of pFF. After a treatment hiatus of 6 or more months, the pFFinduced selective suppression of FSH in circulation was again demonstrable, but only transiently; that is, within 10–14 weeks after the resumption of therapy, even large doses of pFF were no longer effective in reducing serum FSH in these monkeys. One monkey was studied through seven regimens over 4 yr. Accordingly, our series of investigations was divided into three parts. First, we observed that these changing FSH patterns were apparently due to cyclic fluctuations of pFF antibodies in conjunction with the intermittent schedule of pFF administration. The amnestic response to booster injections occurred within 7–14 days, followed by a gradual decline in the anti-pFF titer during succeeding months. Second, we tested ...

Publisher Summary This chapter discusses the role of nonsteroidal regulators in control of oocyte and follicular maturation. The ovarian follicle is bathed in a fluid rich in steroid hormones as well as nonsteroidal regulators which interact to serve to control its maturation, responsiveness to gonadotropins, as well as to lead to control of the maturation of its oocyte. The orderly maturation of an ovarian follicle and its oocyte is controlled by pituitary LH and FSH in concert with local intrafollicular regulators. The principal nonsteroidal follicular regulators are an oocyte maturation inhibitor, a luteinization inhibitor, a luteinization stimulator, FSH receptor binding inhibitor, and inhibin-F. OMI is a polypeptide

Inhibin activity, follicle-stimulating hormone (FSH)-suppressing substance, estrogen, progesterone, and androstenedione were measured in charcoal-treated ovarian tissue and ovarian venous and peripheral blood of eight rhesus monkeys ranging from 12 to 48 months of age. All of the monkeys demonstrated inhibin activity in ovarian tissue, which, if expressed per milligram protein, was relatively constant throughout development. However, if the activity was expressed per ovary, the amount of ovarian FSH-suppressing substance increased between 26 and 48 months; it was present in detectable amounts in ovarian venous blood only in one 26-month-old monkey. Detectable levels of estrogen were present in ovarian venous blood of the 26-month-old and the 48-month-old monkeys but not in the younger monkeys. It is possible that the secretion of inhibin activity may be in part responsible for low levels of serum FSH observed prior to puberty, because it has been observed by others that bilateral ovariectomy in the prepubertal monkey can result in a rise in FSH and that administration of charcoal-treated ovarian follicular fluid can suppress serum FSH in castrated prepubertal and adult rhesus monkeys.

To examine what relationships exist between human follicular fluid inhibin activity and steroid content, follicular fluid was aspirated from 72 follicles at various stages of follicular development. Twenty samples were collected from cystic ovarian follicles, and 50 samples came from normal ovarian follicles. Estrogen, Δ4-androstenedione, testosterone, and progesterone levels in follicular fluid were measured by RIA. Apparent inhibin activity was estimated in follicular fluid samples after charcoal treatment to remove steroids. Each charcoal-treated sample was assayed in triplicate using rat anterior pituitary cultures. Follicular fluid was added at a dose of 2% in the pituitary culture medium, and the ability of the fluid to inhibit basal FSH secretion in the cultures was estimated after a 24-h incubation. The degree of FSH-suppressing activity in the fluid was estimated and expressed in terms of nanoliters of standard porcine follicular fluid inhibin activity per 10 μ follicular fluid. Charcoal-treated ...