Prostaglandins and cellular reaction in uterine flushings. II. Effect of PG synthesis inhibition in IUD users

The effect of oral administration of indomethacin (100 mg/day), a potent inhibitor of prostaglandin (PG) biosynthesis, on the PG levels and cellular profile in the uterine flushings in response to the use of an IUD (Lippes Loop size C) was studied in sixty women. Indomethacin reduced the cell counts in both follicular and luteal phases of menstrual cycles before and after IUD insertion. The anti-inflammatory drug decreased PGE₂ and PGF_2alpha levels in both phases of the cycle before IUD insertion. After insertion, it inhibited only the formation of PGF_2alpha and its 13,14-dihydro-15-keto metabolite in the luteal phase but not in the follicular phase. In long-term users, however, the drugs reduced the levels of all PGs studied in the luteal phase and only PGF_2alpha and its metabolite in the follicular phase. The implications of these findings in the mechanisms of contraceptive action of IUDs and their side effects are discussed.

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Resumen En sesenta mujeres se estudió el efecto de la administración oral de indometacina (100 mg/día), un potente inhibidor de biosíntesis de prostaglandina (PG), en los niveles de PG y en el perfil celular en lavados uterinos, en respuesta al uso de un DIU (Asa de Lippes, tamaño C). La indometacina redujo el contaje celular en ambas fases, folicular y luteal, de los ciclos menstruales antes y después de la inserción del DIU. La droga antiinflamatoria disminuyó los niveles de PGE₂ y PGF_2alpha en ambas fases del ciclo antes de la inserción del DIU. Después de la inserción solamente inhibió la formación de PGF_2alpha y sus 13,14-dehidro-15-keto metabolites en la fase luteal pero no en la fase folicular. Sin embargo, en las usuarias a largo plazo las drogas redujeron los niveles de todas las PG estudiadas en la fase luteal y solamente la PGF_2alpha y sus metabolites en la fase folicular. Se discutieron las implicaciones de estos hallazgos en el mecanismo de la acción anticonceptiva de los DIU y sus efectos colaterales.

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Resumé On a étudié chez 60 femmes les conséquences de l'administration par voie orale (100 mg/jour) d'indométhacine, puissant inhibiteur de la biosynthèse de la prostaglandine (PG), sur les niveaux de PG et le profil cellulaire dans les flux d'elimination utérine en résponse à l'utilisation d'un DIU (stérilet de Lippe, taille C). L'indométhacine a réduit le nombre des cellules tant pendant la phase folliculinique que pendant la phase lutéinique des cycles menstruels avant et après l'insertion du dispositif. Cet anti-inflammatoire a fait baisser les niveaux de PGE₂ et de PGF_2alpha au cours des deux phases du cycle avant l'insertion du stérilet. Après l'insertion, il n'a inhibé que la formation de la PGF_2alpha et de son métabolite 13,14-dihydro-15-cétone pendant la phase lutéinique mais non pendant la phase folliculinique. Toutefois, chez les utilisatrices de longue date, ces substances ont fait baisser les niveaux de toutes les prostaglandines étudiées pendant la phase lutéinique et de la seule PGF_2alpha et son métabolite pendant la phase folliculinique. Cet article examine les liens entre ces constatations et les mécanismes de l'action contraceptive des DIU ainsi que leurs effects secondaires.

     

Cellular response in the uterine cavity after IUD insertion and structural changes of the IUD

The morphology of the exfoliated endometrial cells has been studied with the objective of elucidating the mode of action of an intrauterine contraceptive device. The loose cellular material accumulated in the uterine cavity and on the surface of the IUD was studied in 50 women. The device had been in use for periods of time varying from 24 hours to 84 months. The presumed biologically inert IUD material seems to provoke an acute inflammatory response which is probably the forerunner of macrophage accumulation. The macrophages appear about the third day after the IUD insertion and progressively increase in number in proportion to the duration of usage. Cytomorphological changes were observed in the endocervical smears. Structural changes in the IUD itself also occur.     

Timing of the IUD insertion.

The relationship between the time in the menstrual cycle when a TCu-200 or Cu-7-200 is inserted and subsequent IUD-related events was evaluated. For women who had either TCus or Cu-7s inserted, the pregnancy, expulsion and medical removal rates were similar for insertions performed at any time of the menstrual cycle.     

Postabortal insertion of IUD

Advances in Contraception - During 1983, 823 first trimester therapeutic abortions were performed at the University Hospital of Trondheim, Norway. Of these patients, 229 had an IUD inserted at the...     

宫血宁胶囊预防放置宫内节育器后子宫异常出血的效果

目的:分析宫血宁胶囊预防放置IUD致子宫异常出血的效果。方法:应用meta分析方法的固定效应模型,对国内1990～2010年采用宫血宁胶囊预防放置IUD致出血副反应,并以空白或安慰剂对照的随机分组研究进行定量合并分析。结果:治疗组1168例患者中87例经量增多或经期延长,对照组1168例患者中392例经量增多或经期延长。合并优势比(OR)=6.79,95%置信区间(CI)为5.25～8.78,两者间差异有统计学意义(合并效果检验统计量Z=14.58,P<0.001)。结论:宫血宁胶囊预防放置IUD出血副反应的效果肯定,可以显著减少经量增多和经期延长的发生。     

重复放置宫内节育器并节育器异位4例临床分析

目的 探讨重复放置宫内节育器（ IUD）并IUD异位的原因及处理。方法 回顾分析陕西省妇幼保健院4例重复放置宫内IUD并IUD异位患者的临床资料。结果 3例患者经腹腔镜取出异位的IUD,其中1例患者因IUD与周围组织粘连分离困难而中转开腹,患者均手术过程顺利,无术中及术后并发症。另1例患者因无明显不适而拒绝手术。结论 对于放置IUD患者应定期随访观察IUD位置,可疑IUD异位者应进一步确诊检查,以避免重复放置IUD或IUD异位危害患者健康。     

The cellular composition of uterine fluid in IUD users — A quantitative study

The cellular composition of uterine fluid was studied quantitatively in 75 IUD users and 48 non-users. In the IUD group the number of granulocytes was increased about 300 times above that of the non-IUD group, whereas the numbers of mononuclear phagocytic cells and lymphocytes were increased by a factor of 30. Endometrial glandular cells were not quantitatively affected by the presence of an IUD. Granulocytes constituted nearly two-thirds and mononuclear phagocytic cells nearly one-third of the total cell count in the IUD group. Mast cells were found more frequently and eosinophilia occurred more often in the uterine fluid of IUD users.     

Effect of IUD on urokinase-like immunoreactivity and plasminogen activators in human uterine fluid

The coexistence of two types of plasminogen activators in human uterine fluid was demonstrated. Immunologically, one was urokinase-like and the other tissue activator-like. Both activators contributed to the fibrinolytic activity of uterine fluid. Urokinase-like immunoreactivity decreased from the proliferative phase to the luteal phase and increased premenstrually. The increase in fibrinolytic activity premenstrually was ascribed mainly to an increase in concentration of the urokinase-like plasminogen activator.A much higher urokinase-like immunoreactivity was found in the uterine fluid from IUD-users than from non-users. The fibrinolytic activity of the uterine fluid, which in contrast to that of the endometrium is known to be depressed in IUD-users, was inhibited by an antiserum against the tissue activator but only weakly influenced by an antiserum against urokinase. This indicates the presence of urokinase inhibitors in the uterine fluid of IUD-users with a capacity to inhibit the enzymatic activity of the urokinase-like plasminogen activator.     

Comparison of intramenstrual IUD insertion with insertion following menstrual regulation

To evaluate the use-effectiveness and safety of IUD insertion immediately after menstrual regulation (MR) for delayed menses, a Lippes Loop D (LLD) intrauterine device was inserted in each of 100 consecutive clients at the University College Hospital, Ibadan, immediately after menstrual regulation. Pertinent event rates after 12 months of use were compared with those of 100 consecutive women who had the LLD inserted during menstruation. The cumulative net expulsion rate after 12 months of use was 8% for the study group and 4% for the controls. The overall rate of removals was 15% for the study group and 16% for the control group. None of the observed differences was statistically significant. The continuation rates at 12 months were comparable for both groups (78% and 80%, respectively). There were no accidental pregnancies during the study period. The authors suggest that IUD insertion immediately after menstrual regulation is as effective and safe as intramenstrual insertion, provided prophylactic antibiotics are given.

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Resumen Para evaluar el uso, efectividad e inocuidad del DIU insertado inmediatamente después de la regulación menstrual (RM) por atraso en menstruar, se insertó un dispositivo intrauterino, el Asa de Lippes (LLD) en cada una de 100 clientas consecutivas del University College Hospital en Ibadan, inmediatamente después de la regulación de la menstruación. Luego de 12 meses de uso, las tasas de eventos pertinentes fueron comparadas con aquellas de 100 mujeres consecutivas a las que les fuera insertado el LLD durante la menstruación. La tasa acumulativa neta de expulsión después de 12 meses de uso fué de 8% para el grupo estudiado y de 4% para el grupo control. La tasa general de remociones fué de 15% para el grupo estudiado y de 16% para el grupo contro. Ninguna delas diferencias observadas fué estadísticamente significativa. La tasa de continuidad a 12 meses fué comparable en ambos grupos (78% y 80% respectivamente). No hubo embarazos accidentales durante el período del estudio. Los autores sugieren que la inserción de los DIU inmediatamente después de la regulación menstrual es tan efectiva e inocua como la inserción intramenstrual siempre que se administren antibióticos profilácticamente.

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Resumé Pour évaluer l'efficacité et l'innocuité de la mise en place d'un DIU immédiatement après les règles, on a mis en place un DIU Lippes Loop D (LLD) chez 100 patientes consécutives, immédiatement après les règles, à l'University College Hospital d'Ibadan. On a comparé le taux d'événements pertinents au bout de 12 mois d'utilisation au taux enregistré chez 100 femmes consécutives, chez lesquelles le DIU avait été mis en place pendant les règles. Le taux cumulé net d'explusion après un an d'utilisation a été de 8% dans le groupe étudié contre 4% dans le groupe témoin. Le taux global de retrait a été de 15% dans le groupe étudié contre 16% dans le groupe témoin. Aucune des différences observées n'était statistiquement significative. Le taux de poursuite au bout de 12 mois était comparable dans les 2 groupes (78% et 80%, respectivement). Il n'y a eu aucune grossesse non désirée pendant la période d'étude. Les auteurs estiment que l'insertion d'un DIU immédiatement après les règles est aussi efficace et sûre que l'insertion pendant les règles, à condition de prescrire une antibiothérapie préventive.

     

Evaluation of postabortion IUD insertion in Egyptian women

This study was carried out at Alhussein University Hospital and Elmonera General Hospital to assess the safety and efficacy of intrauterine device (IUD) insertion immediately after spontaneous abortion compared with insertion 2 weeks after abortion. One hundred women between ages 18 and 40 years were recruited from those admitted via the emergency room with first trimester spontaneous abortion. All women were counseled about a method of contraception, particularly copper T-380, and divided into two groups: Group I, which included 69 women who preferred immediate IUD insertion, and Group II, which included 31 women who asked for late IUD insertion 2 weeks after an abortion. All women were followed at 2, 6, and 10 weeks after insertion of IUDs. Bleeding patterns were comparable in both groups. Mild bleeding occurred in 9.2% and 16% in Groups I and II, respectively; moderate bleeding occurred in 80% and 64%, respectively, and severe bleeding was observed in 10.8% and 20%, respectively. This was not significant. Expulsion rate was 4.5% and 3.4% in Groups I and II, respectively, which was also not significant. There were no cases of perforation or pelvic infections. This study showed that insertion of an IUD immediately after a spontaneous abortion is safe and could be offered to those who have had an abortion and who ask for a method of contraception.     

Immediate postabortal insertion of a levonorgestrel-releasing IUD

Experimental IUDs releasing only 10 μg levonorgestrel per day and established copper-releasing IUDs (Nova-T) were inserted in 60 women in connection with legal first-trimester abortion. Bleeding and spotting and other events were recorded during the first year. Restoration of the menstrual cycle was studied. Blood samples were collected twice a week over a three-month period from five women receiving a levonorgestrel-releasing IUD to determine plasma levels of estradiol, progesterone, levonorgestrel, LH and FSH. FSH showed an increase approximately ten days (range 4–19) after abortion. LH/hCG concentrations reached a plateau approximately 24 days (range 9–42) after abortion. Initially, levonorgestrel concentrations were two-fold compared with concentrations of 90 pg/ml after four weeks. After four weeks the plasma levonorgestrel concentrations were stable. All five women had an ovulatory menstrual cycle. The first periods occurred 35 days after operation in the levonorgestrel-IUD group and 30 days after operation in the Nova-T group. The median duration of bleeding and spotting after the insertion was 12 days (range 3–26) in the Nova-T group and 12.5 days (range 3–93) in the levonorgestrel-IUD group. The difference was not statistically significant. From the second month on, menses-like bleeding was more common in the copper-releasing IUD group than in the levonorgestrel-IUD group. The difference was statistically significant (p < 0.001). After one year 75 percent of the patients continued with their IUDs in both groups. One pregnancy occurred in the experimental levonorgestrel-IUD group. One total expulsion was noticed in both groups, and one partial expulsion in the levonorgestrel-IUD group. Two levonorgestrel-IUDs and four Nova-Ts were removed because of bleeding and/or pain. One infection was noticed in the whole group six days after the operation. In the levonorgestrel-IUD group 74 percent of the women had a regular cycle after one year, while all Nova-T patients had a regular cycle. Twelve percent (7 women) were lost to follow-up at one year. The results of this study suggest that a levonorgestrel-releasing IUD can be inserted after legal first-trimester abortion and the results are comparable with those of previous studies that have been made using copper-releasing IUDs.     

IUD insertion practices in the United States and Puerto Rico, 1973.

Retrospective reports on IUD insertions during the first 6 months of 1973 were provided by 16,893 physicians residing in the U.S. and Puerto Rico. This was 48.9% of the physicians listed in the master files of the American Medical Association and the American Osteopathic Association as having an interest in obstetrics and gynecology, public health, general preventive medicine, or family practice. Information elicited by interviews with 1% of the nonrespondents mirrored that of the respondents. It is estimated that in the 6-month period there were 810,000 IUD insertions. Regional rates varied from a high of 27.3/1000 in parts of the West to 11.8-12.4/1000 in the Midwest. The rate for the nation was 18/1000. The percentage of nonprivate patients receiving IUDs varied substantially by region, too. 85% of all insertions were do ne by physicians; 6% by paramedical personnel. 90% of the physician-inserted IUDs were by doctors whose primary specialty was obstetrics-gynecology and more than 75% were by doctors engaged in direct patient care. Rates of insertion by individual physicians varied greatly. 1% of the obstetricians-gynecologists averaged more than 8 insertions a week.     

Post-partum bleeding and infection after post-placental IUD insertion

The incidence of excessive bleeding and endometritis in 145 women who accepted post-placental insertion of a copper T380A intrauterine device (IUD) was compared with that of 157 subjects who did not accept the insertion of the IUD. The subjects delivered at the Maternidade da Encruzilhada, Recife, Brazil in the period from March 30, 1994, to December 15, 1995. A blood sample for hemoglobin was collected before placental expulsion and 10 days after labor. The IUD was inserted up to 10 min after the expulsion of the placenta. There was no difference between the groups in the incidence of excessive bleeding, neither regarding mean hemoglobin concentration before placental expulsion (t = 0.039; p = 0.83) nor at day 10 postpartum (t = 1.04; p = 0.29). There were 5 cases of clinically diagnosed endometritis among the 145 subjects with placental-IUD (3.4%) and 7 cases among the 157 women without IUD (4.6%) (p = 0.40). Post-placental insertion appears to be a convenient approach to IUD initiation, with no observed increase in the incidence of excessive bleeding or endometritis.     

Composition of uterine flushings from Large White and prolific Chinese Meishan gilts

This study examined differences in selected components of uterine secretions from Large White and prolific Chinese Meishan gilts during the oestrous cycle or early pregnancy. Total recoverable protein, uteroferrin (measured as acid phosphatase activity), acyl aminopeptidase, calcium, sodium, potassium, immunoglobulins A and G, glucose, fructose, oestradiol-17 beta, and prostaglandins F2 alpha (PGF2 alpha) and E2 (PGE2) in uterine flushings were measured. During the oestrous cycle, breed effects were detected only for total protein (P = 0.07), which tended to be higher for Large White gilts. However, for pregnant gilts, total recoverable glucose (P less than 0.05), fructose (P less than 0.05) sodium (P less than 0.05), immunoglobulin A (P less than 0.01), PGF (P less than 0.01), PGE (P less than 0.01), and acyl aminopeptidase (P less than 0.05) were greater in uterine flushings from Meishan gilts. Only uteroferrin was higher (P = 0.06) in uterine flushings from Large White gilts. Concentrations of prolactin were higher (P less than 0.05) in plasma from cyclic or pregnant Meishan gilts, but concentrations of total oestrogens and progesterone were not affected by pregnancy status or breed. These results suggest that Meishan conceptuses, individually or collectively, are more stimulatory to endometrial secretion and/or transport of the components of histotroph into the uterine lumen, or that the endometrium of Meishan gilts is more sensitive to conceptus signals responsible for the accumulation of histotroph in the uterine lumen.     

Perforation of the uterus following IUD insertion in the puerperium

Perforation of the uterus by an IUD is very rare. However, during the puerperium when the uterus is small and the uterine wall is thin the risk of perforation increases. We present three patients treated within a rather short period of time at our institution for perforation of the uterus caused by IUD insertion 3–4 months after delivery. Although perforation is by no means always associated with pain, our patients did present with abdominal pain caused by this rare IUD-associated complication. One patient underwent laparotomy, and in two, laparoscopy sufficed to treat this complication.

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Resumen La perforación del útero por un DIU ocurre muy rara vez. Sin embargo, el riesgo de perforación aumenta durante el puerperio, cuando el útero es pequeño y la pared uterina delgada. El artículo presenta tres casos de pacientes tratadas en nuestro establecimiento por una perforación de útero tras la inserción de un DIU 3 ó 4 meses después del parto y que se produjeron con poco intervalo. Si bien una perforación no va siempre acompañada de dolores, nuestras pacientes experimentaban dolores abdominales causados por esta rara complicación asociada con los dispositivos intrauterinos. Una paciente debió ser sometida a una laparotomía y, en el caso de las otras dos, fue suficiente una laparoscopia para tratar esta complicación.

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Resumé La perforation de l'utérus par un DIU se produit très rarement. Toutefois, le risque de perforation augmente pendant la période de puerpéralité, lorsque l'utérus est petit et que sa paroi est mince. L'article présente trois cas de patientes traitées dans notre établissement pour une perforation de l'utérus après insertion d'un DIU 3 à 4 mois après l'accouchement et qui se sont produits à peu de temps d'intervalle. Bien qu'une perforation ne soit pas forcément toujours accompagnée de douleurs, nos patientes étaient affligées de douleurs abdominales dues à cette rare complication liée aux dispositifs intra-utérins. L'une d'elles a dû être laparotomisée et pour les deux autres, la laparoscopie a suffi pour traiter cette complication.

     

IUD insertion forces: effects of recent childbirth and lactation

This investigation compared the force required to insert an IUD in women who were breastfeeding and who had recently delivered a child with that required in control women who were not breastfeeding and who had not recently delivered. Twenty-eight women who had recently delivered and who were breastfeeding were compared with twenty-eight controls. The women were matched for age and parity and for the type of IUD used. The mean IUD insertion force in the breastfeeding, recently-delivered women was 1.75 newtons (N) as compared to 2.80 N in the controls. The difference was statistically highly significant (pairedt-test,p<0.01). Recent childbirth and lactation are associated with a reduction in IUD-related insertion pain, probably due to a reduction in the force required for insertion. This reduction in IUD insertion force is not necessarily related to lower uterine perforation rates in IUD insertion in this group. A number of physiological mechanisms may be responsible for this finding.

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Resumen Esta investigacion comparó la fuerza requerida para insertar un DIU en mujeres amamantando y que habían parido recientemente, con mujeres de control que no amamantaban ni habían parido recientemente. Veintiocho mujeres que habían parido recientemente y amamantando fueron comparadas con veintiocho controles. Las mujeres fueron apareadas por edad y paridad y por el tipo de DIU usado. La fuerza media de inserción de un DIU en la mujer que había parido recientemente y estaba amamantando, fué de 1.75 newtons (N) comparada con 2.80 N en los controles. La diferencia fué estadísticamente altamente significativa (t-test apareado,p<0.01). Lactancia y reciente paridad están asociadas con la reducción en el dolor relacionado a la inserción del DIU. Esta reducción en la fuerza de inserción no está necesariamente relacionada con las tasas de perforación uterina baja en la inserción de un DIU en este grupo. Un número de mecanismos fisiológicos podrían ser responsables de este hallazgo.

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Résumé On a cherché à comparer la force nécessaire pour insérer un DIU chez des femmes qui allaitaient et avaient récemment mis au monde un enfant et chez des femmes qui n'allaitaient pas et qui n'avaient pas récemment accouché. La comparaison portait sur vingt-huit femmes dans un cas comme dans l'autre. On a veillé à faire corresponde les deux séries du point de vue de l'âe, du nombre de grossesses antérieures et du type de DIU utilisé. Chez les femmes allaitant et ayant récemment accouché, la force nécessaire pour insérer un stérilet était en moyenne de 1,75 newton (N), au lieu de 2,80 N chez les sujets témoins. Cette différence est très significative du point de vue statistique (t test sur séries appariées, p<0,0.1). Un accouchement récent et l'allaitement sont associés à une réduction des douleurs causées par l'insertion d'un DIU, probablement du fait que la force nécessaire pour pratiquer cette opération est moindre. Cette réduction de la force d'insersion n'est pas forcément liée à des taux inférieurs de perforation utérine lors de l'insersion d'un DIU dans ce groupe. Il est possible qu'un certain nombre de mécanismes physiologiques soient responsables des faits ainsi constatés.