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Effect of lengthening the fallopian tube on fertility in the rabbit.

The effect of surgically lengthening the rabbit oviduct was investigated. In the study group, a lengthened fallopian tube was created by division of the left fallopian tube at the ampullary-isthmic junction and the right fallopian tube at the uterotubal junction. The proximal left tube and the entire right tube were mobilized to the midline, and a microsurgical anastomosis was performed with 10-0 nylon. This formed a tube that was lengthened by approximately 50%, with doubling of the isthmic region. In the control group, both tubes were divided at the ampullary-isthmic junction, and the proximal left and distal right segments were joined to form a tube of normal length. The left ovary and ampulla were resected in both groups. After the animal had been bred, a second laparotomy was performed to assess adhesion formation, document tubal patency, and establish a nidation index. The median nidation index of the control group (N = 11) was 0.89, whereas that of the lengthened group (N = 7) was 0. The nidation indices of the two groups were different, with P less than 0.01.

Animals↗

The effect of training in microsurgery.

One of the most important and fundamental prerequisites for successful microsurgery is serious and adequate training. This article presents the effect of microsurgical training on the functional end result of reanastomosis in the rabbit fallopian tube and evaluates the appropriate duration of laboratory training. In 50 New Zealand White female rabbits a microsurgical reanastomosis of the fallopian tube in its isthmic portion was performed. The rabbits were divided into five groups. In the first group only 30% of the rabbits conceived on the side operated on. The nidation index was only 0.269 as compared to 0.831 for the control side. Improvement in microsurgical skill following 100 isthmic anastomoses resulted in a 100% pregnancy rate for the last group. The nidation indexes in this group were the same on the side operated on and on the control side, 0.774 and 0.702, respectively. Scanning electron microscopic examination of the anastomosis site revealed a progressive increase in patency rate and in the amount of apposed mucosal folds in the three groups. A training program is recommended, which should bring about a nidation index and pregnancy rate that should not differ from the side operated on to the control side.

Animals↗

Endometrial and myometrial effects of progesterone antagonists in pregnant guinea pigs.

Three antiprogestogens of the RU 38.486, ZK 98.734, and ZK 98.299, were studied at different stages of pregnancy in the guinea pig. Treatment starting on postconception day 4 completely prevented nidation; all three compounds had comparable inhibitory potency. Treatment after nidation, starting on postconception day 8, induced decidual collapse and bleeding, but embryonic tissue was retained in nidation sites. In contrast to results in animals in nonfertile cycles, luteolysis was not induced, indicating that antiprogestogens lack the ability to induce uterine prostaglandin synthesis/liberation. On postconception day 43, RU 38.486 showed marginal abortifacient activity. The other compounds induced expulsion more rapidly and at a higher rate. The comparatively pronounced antiglucocorticoid activity of RU 38.486 may account for this difference. With RU 38.486, a high level of uterine prostaglandin sensitivity and a cervical ripening were induced consistently and fast; spontaneous labor, on the other hand, occurred after several days, if at all. Complete uterine evacuation was induced within hours by otherwise inactive doses of sulprostone in various combinations with ZK 98.299 RU 38.486 but surprisingly not with ZK 98.734. A single dose of ZK 98.299 induced an approximately thirtyfold increase in uterine prostaglandin sensitivity within 24 hours, exceeding that present before term, but did not induce spontaneous labor. This is evidence that endogenous prostaglandins were not activated, analogous to perinidation stages. Observation of antiluteolytic activity of antiprogestogens in nonpregnant animals is considered of major theoretical importance in this context. It seems that inhibition of progesterone leads to suppressed uterine prostaglandin liberation. The same effect in pregnancy could explain the inability of the uterus to expel a seriously compromised conceptus. In conclusion, we suggest that progesterone is a stimulator rather than a depressor of uterine prostaglandins in the late luteal phase and pregnancy. The ability of the conceptus to neutralize this stimulatory action of progesterone is considered to be essential for the rescue of the corpus luteum and uterine motor quiescence in the guinea pig. The clinical significance of these findings is that the high frequency of incomplete abortions and protracted, sometimes heavy bleeding in pregnant women treated with RU 38.486 may reflect decidual compromise and simultaneous uterine prostaglandin deficiency, as found in our animal model after progesterone blockage.

Abortion, Induced↗

Conventional and simplified microsurgical isthmic tubal anastomosis compared in the rabbit.

Because the fallopian tube has potential for spontaneous recanalization, a simplified technique for isthmic anastomosis has been previously proposed. This study compares the simplified technique, which uses only one suture to approximate the tube, with a conventional isthmic anastomosis. The nidation index and patency rate subsequent to these procedures on the rabbit oviduct were evaluated. The conventional anastomosis gave a significantly better nidation index (P less than 0.01) and a patency rate (P less than 0.05). Even when tubal patency was established with the simplified technique, the nidation index may have been less than with conventional anastomosis (P less than 0.07). Gynecologic microsurgeons should continue to strive for the best anatomic repair possible when performing isthmic anastomosis and not rely on the fallopian tube's potential for spontaneous recanalization.

Animals↗

Reproductive toxicity of cabergoline in mice, rats, and rabbits.

Cabergoline, a new dopaminergic ergot derivative with potent long-lasting prolactin (PRL)-lowering properties, was assessed using standard reproductive studies in the mouse, rat, and rabbit with oral administration. Because of the compound's pharmacologic activity, several aspects remain incompletely explored in the rat, in which prolactin is the luteotrophic hormone. A fertility study in female rats was possible only at very low doses (0.5, 1, and 2 micrograms/kg/d) because higher doses completely inhibited implantation. In male rats no adverse effects were seen on male reproductive performance or on the offspring at doses up to 320 micrograms/kg/d given for 10 weeks prior to mating with untreated females. In a developmental toxicity study in rats treated from day 6 to day 15 of gestation at doses (6.25, 12.5, and 25 micrograms/kg/d) not exceeding the active dose for inhibition of egg nidation (ED50 = 25 micrograms/kg), a high incidence of total litter loss occurred as a reflection of inhibition of egg nidation at the highest dose, but embryofetal development was not impaired in litters reaching term. An exploratory study at 30 or 1000 micrograms/kg/d with treatment from day 5 of gestation or later demonstrated that cabergoline did not affect the maintenance of pregnancy at 30 micrograms/kg/d given from day 7 or later, or at 1000 micrograms/kg/d given from day 9. Doses of 500, 2000, and 8000 micrograms/kg/d (treatment from day 6 to day 15 of gestation) did not inhibit egg nidation in mice and showed no adverse effects on intrauterine development. Doses ranging from 5 to 8000 micrograms/kg/d administered from day 6 to day 18 of gestation in the rabbit were associated with maternal effects, including a reduction in body weight gain and food and water intake starting from 500 micrograms/kg/d and increased reactivity at the highest doses (4000 and 8000 micrograms/kg/d). Effects on intrauterine development were restricted to a reduction in mean fetal and placental weights at 4000 and 8000 micrograms/kg/d. In peri- and postnatal studies in rats (treatment from day 15 or 17 of gestation to weaning) cabergoline did not affect fetal development and parturition up to 100 micrograms/kg/d, but strongly inhibited milk secretion starting from 10 micrograms/kg/d, thus leaving unexplored the postnatal phase at higher doses. When neonatal rats (born from untreated dams) were treated directly with cabergoline at 10, 30, and 90 micrograms/kg/d from day 7 to 13 after birth, treatment was well tolerated up to the highest dose tested (90 micrograms/kg/d). It was concluded that cabergoline did not impair fertility in the male rat, was not teratogenic in mice and rabbits, did not affect the latter phase of gestation or parturition in the rat, and was not toxic when administered directly to neonatal rats.

Animals↗

Interceptive activities of STS 557 in rabbits, mice and rats.

STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) is a interceptive agent in rabbits, mice and rats. In rats, it also shows post-implantational pregnancyterminating activity. In rabbits treated orally before mating or after ovulation for three consecutive days, it inhibited pregnancy largely at total doses of 0.08 mg/kg in the former and completely with 8.0 mg/kg in the latter case. A single subcutaneous dose of 40 mg/kg given on day 1 of pregnancy inhibited completely nidation in rats. In inhibition of pregnancy in rats could also be realized when the dose of 40 mg/kg was distributed on several days and given subcutaneously at daily doses of 5.0 mg/kg on days 1--8 of pregnancy, and even only daily doses of 2 mg STS 557/kg were needed in this respect, if animals which showed no living conceptuses were scored as "non-pregnant". STS 557 was effective in terminating pregnancy in rats, too, when given subcutaneously after implantation for 4 days at daily doses of 50 mg/kg, beginning on day 5 or on day 8 of pregnancy. The nidation inhibiting effects of STS 557 in rabbits treated pre-coitally, and in mice as well as in rats treated post-coitally were more marked than those of levonorgestrel. The interceptive and post-implantational inhibiting activity of STS 557 may be based on its antiprogestagenic properties. Luteolysis in the nidation phase can be excluded as shown by radioimmunoassay of progesterone in rats. The antigestagenic effects on the endometrium in rats were evident in the diamine oxidase assay. The acceleration of tubal egg transport, the morphological changes of the endometrium shown by scanning electron microscopy, and the effects on blastocyst transfer, all investigated in rats, suggest peripheral mechanisms of action.

Amine Oxidase (Copper-Containing)↗

[Determining implantation time frame of the trophoblast by hCG level monitoring].

Although the implantation of a human trophoblast cannot be directly observed, in-vitro fertilization permits examination of the factors accompanying the nidation of the trophoblast. Against this background, the question arises: at what point in time does the nidation of the human embryo take place in the endometrium of the uterus? In this study, we investigated 104 pregnancies which had resulted from in-vitro fertilization. The course curves of the HCG serum concentration were drawn up and then set in relation to the course of the pregnancy. By means of a regression analysis, we established the time point at which nidation occurred. In pregnancies carried through to delivery, the implantation happens, on the median, 6.6 days after the follicle puncture. The implantation window lies between 5.9 and 7.5 days (25th to 75th percentile). In the case of abortions, the median is 7,0 days (after follicle puncture), and for extra-uterine pregnancies it is 8.1 days (after follicle puncture). This shows that implantations in pathological pregnancies take place at a larger point in time.

Abortion, Spontaneous↗

[Triple extra-uterine pregnancy following in vitro fertilization and embryo transfer].

The article reports on an ectopic pregnancy after IVF/ET that was characterized by the simultaneous nidation of three of the four transferred pre-implantation embryos in both (heavily damaged) Fallopian tubes. The ectopic nidation not only in one of the Fallopian tubes must be seen as a pointer to the importance of active mechanisms of transport from the cavum into the Fallopian tubes. Therefore it is unlikely that ectopic pregnancies after IVF/ET--even if the technique is satisfactory--can be avoided completely. In view of the fact that several IVF treatments were performed in vain, the nidation of three of the four transferred embryos must be interpreted as supporting the theory that the conditions in the Fallopian tubes are more favourable for the development of the human pre-implantation embryos.

Adult↗

[A study of progestin, glucocorticoid binding and glycogen content in rat endometrium before and after implantation: effect of antiprogesterone RU-38486].

Pregnant rats were injected with 3H RU38486 into the uterine cavity on day 2, 4, 5 and 8 of pregnancy. Before implantation, the saturable RU binding increased significantly (day 2 vs. 4; 30.0 +/- 2.3 vs. 640.0 +/- 17.9 dpm/g, p less than 0.001). After implantation, the binding became higher at the nidation site (implantation vs. non-implantation site; 1156.1 +/- 237.1 vs. 595.0 +/- 24.3, p less than 0.001, day 5). The dexamethasone suppressive RU binding, on the other hand, showed no significant increase during day 4, 5 and 8. Daily administration of RU38486 during day 4 and 8 caused failure to implant or to develop normal conceptus. The endometrium in these RU treated animals was stained for tissue glycogen and studied light microscopically. The tissue glycogen content appeared to be markedly decreased in RU treated animals but only at the site of implantation. The decrease was observed in both decidua and trophoblasts but not in myometrium or decidual epithelium. The present results indicate; (1) In rats, endometrial progesterone binding increases prior to implantation. (2) After implantation, the nidation site further increases its saturable progesterone uptake compared to the non-implantation site. (3) When normal process of implantation is inhibited by RU38486 administration, there occurs a decrease in the glycogen synthesis at the nidation site, including decidua and trophoblasts.

Animals↗

[Is preimplantation diagnosis legal?--on the need for harmonizing legislation].

Whether PGD is already legally permitted in Germany today is a moot point. A guidelines draft of the Germany's Federal General Medical Council, the Bundesärztekammer, on pre-implantation genetic diagnostics that--like the earlier findings of the ethics commission of the German federal state of the Rhineland-Palatinate--assumed that the method is admissible, if certain clearly-defined indications are present and a rigorous testing procedure has been established, has given the discussion a new impetus. The discussion is in full swing, with calls by politicians for the legislator to pass a regulation mounting. Of late, though, constitutional objections have been raised against a positive-law regulation. Such a simple legal move to regulate PGD, it is claimed, would violate the constitutionally-guaranteed right to inviolable human dignity. Critics, however, point out that such an absolute inviolability does not exist. According to them, not only the verdicts by the German Federal Constitutional Court, the Bundesverfassungsgericht, on the reform of section 218 of the German Federal Penal Code (StGB)--the paragraph that specifies the conditions under which an abortion is not punished--that relativize (in terms of the indication model) one claim to existence with respect to another, but also the approval in terms of pharmaceutical and medicine-products law of nidation-blocking agents, serve to show this. If the condition of being a human being were made to coincide with the completion of the genetic code upon the completion of the process of fertilisation, then one tended to forget, the critics noted, that this attendant dignity was not properly "infused with life" unless nidation had been successful. Without nidation everything were fragmentary, the total protection of human dignity according to Article 1 Section 1 of the Federal Republic's Basic Law, Germany's constitution, notwithstanding. During every in vitro fertilisation embryo transfer is conditional upon a variety of factors the presence of which is not noted until after fertilisation has taken place. On the part of the embryos, too, certain conditions have to be met whose presence at the moment of fertilisation is not assured. Thus an embryo with, for instance, defects that can be visually detected will not be transferred. With regard to these facts too the opponents of pre-implantation genetic diagnostics must be challenged to answer the question of why an embryo with visually-detectable defects should undoubtedly be allowed to be discarded, but the act of searching for "internal" defects be banned. Thus the fact remains that the mere acceptance of the loss of created embryos does not make artificial insemination a punishable offense, as long as the motive for the act is to bring about pregnancy. To achieve legal security for the couples and the physicians involved the law on the protection of embryos should be changed. The new regulations should determine under which conditions PGD is permissible. As is already the case for other norms that apply to reproductive medicine, but also for the practice of abortion, these regulations should contain an analogous right of refusal for the professionals involved. The laws relating to the healing professions, to the professional chambers, as well as the regulations of the various German federal states (which together constitute the Federal Republic of Germany) that apply to the professions should be amended accordingly.

Abortion, Induced↗

Scanning electron microscopy in gallstone research.

Nidation of gallstones by inorganic or organic Ca salts was studied in 336 consecutive cases by SEM/EDXA and additional methods (X-radiography, X-diffraction, IR spectroscopy). SEM/EDXA proved to be a useful method in studying very small radio-dense nuclei, since common means of phase analysis are limited because of the small amounts of material to be analyzed. In 20.3% stones had radio-dense nuclei composed of either Ca-phosphate- and/or Ca-carbonate microcalculi. Ca-palmitate and/or pigments were at the centre of stones showing a less dense X-shadow. Nidation of cholesterol stones by defined pigment microcalculi was observed in 10 cases. Microstructures, for instance Ca-carbonate- and pigment microcalculi of identical structure to the central nidi, were found in corresponding bile sediments, confirming the role of such structures in gallstone nidation. Two structural features were identified in pigment stones: small, irregular granules, and glassy, poorly structured masses. Ca-bilirubinate calculi were built up from granules while the so called 'black' stones were composed entirely of the glassy masses or contained both structural elements, indicating that bilirubinate may be involved in the formation of some black stones, too. As revealed by EDXA and EPMA Ca was predominant in both subtypes while the black stones additionally contained Cu, Fe and, above all, considerable amounts of S. the latter was found to be in a low, non-SO4-valence state.

Bile↗

Composition of pigmented centers of cholesterol gallstones.

Most cholesterol gallstones have visually pigmented centers, but it is unclear whether this represents simple co-precipitation of pigment with cholesterol during stone nidation or nidation on a true pigment stone center. To clarify this issue, we selected from among 67 sets of cholesterol gallstones, 12 sets with the most conspicuously pigmented centers. The composition of the centers and the peripheries of these 12 stones was analyzed using infrared spectroscopy and compared with that of 10 black pigment gallstones. The pigmented centers of cholesterol stones contained 80.1 +/- 7.9% (mean +/- S.E.) cholesterol, 6.2 +/- 3.4% calcium bilirubinate (only 4 of the 12 centers had measurable calcium bilirubinate), trace amounts of calcium phosphate and no calcium carbonate or calcium palmitate. The peripheral areas of the cholesterol stones contained 91.6 +/- 2.3% cholesterol and no detectable calcium salts. For comparison, the composition of the centers of 10 black pigment gallstones was 13.5 +/- 2.2% cholesterol, 28.2 +/- 5.3% calcium bilirubinate, 5.5 +/- 2.4% calcium phosphate and 10.6 +/- 5.8% calcium carbonate. The composition of only one cholesterol stone center (15.8% cholesterol, 26.8% calcium bilirubinate) resembled that of a pigment stone, but even this center differed from that of a typical pigment stone in that it contained only a trace amount of calcium phosphate and no calcium carbonate. Thus, the chemical composition of pigmented centers of cholesterol gallstones is quantitatively different from that of black pigment stones, suggesting that cholesterol gallstones do not form on a pigment stone nidus.

Bilirubin↗

Fertility and histology after rabbit ovarian wedge resection with CO2 laser or electrocautery using posterior reconstruction with nylon or polyglactin sutures.

In an experimental study in rabbits, the CO2 laser and electrocautery were compared in performing microsurgical ovarian wedge resection; polyglactin and nylon sutures were compared for ovarian reconstruction. Histologic reaction, adhesion formation, and functional parameters (number of corpora lutea, number of pregnancies, nidation index) were evaluated 30 and 90 days postoperatively. Thirty days after surgery, the tissue inflammatory response was very similar in the four groups; fibrosis was not detected. Significant reductions (P less than 0.01) were found for the experimental (operated right ovary) vs. the control (unoperated left ovary) groups when comparing the number of corpora lutea and the number of pregnancies. No significant differences in the nidation index were demonstrated. Adhesion formation was not different between any of the experimental procedures; adhesions were not detected in the control ovaries. At 90 days, the polyglactin suture was entirely absorbed and no inflammatory reaction persisted. Minimal giant cell infiltration was found around the nylon suture. The histologic differences between the two sutures were statistically significant (P less than 0.02). No fibrosis was observed. The functional parameters did not reveal statistically significant differences between the two sutures.

Animals↗

The status of the corpus luteum during pregnancy in Miniopterus schreibersii (Chiroptera: Vespertilionidae) with emphasis on its role in developmental delay.

Developmental delay is correlated with torpor in the temperate zone bent-winged bat, Miniopterus schreibersii (latitude 37 degrees S) as a period of pre-implantation delay (delayed implantation) followed by a short post-implantation delay (delayed development). During this time, the number of steroidogenic organelles in luteal cytoplasm is greatly reduced compared with normal embryogenesis, and granular endoplasmic reticulum is prominent. Nidation, which occurs while the animals are hibernating, is not accompanied by marked changes in luteal ultrastructure, although the number of lipid droplets decreases somewhat. Progesterone rises slightly but not significantly; however, a pre-nidation decrease in high 17 beta-estradiol levels may play a role in implantation. Following implantation, the conceptus remains delayed at the blastocyst stage for several weeks. During this time the bats remain torpid and the only change in luteal cell ultrastructure is an increase in smooth endoplasmic reticulum as differentiation begins toward the trilaminar stage. At the end of developmental delay hypertrophy of the luteal cell begins and mitochondria and lipid droplets increase, markedly. By this time arousal from hibernation has occurred, placentation takes place and normal development is underway. At placentation, smooth endoplasmic reticulum reaches its maximum in luteal cytoplasm; estrogen and progesterone levels peak about 6 weeks later. For the remaining 2 months of gestation, signs of luteolysis appear. These observations suggest that the corpus luteum of developmental delay, though sub-optimally functional, is prolonged in its luteinization by the arrival of winter when the bats enter torpor. The capacity for maximal steroidogenesis is acquired at the end of winter, some weeks after implantation, when arousal occurs and normal development ensues.

Analysis of Variance↗

Experimental study of transductal dissemination of cancer of the pancreas.

Experimental studies on the mechanims of transductal dissemination of the pancreas carcinoma was made in rabbit by injection of VX2 carcinoma suspension into the pancreatic duct. Ductal occlusion was conductive to nidation and growth in the pancreas of intraductal floating cancer cells, but tumor growth also occured in 40% of animals in which the duct was not occluded. The mechanisms of nidation in the pancreas of intraductal floating cancer cells were direct embedding into the ductal wall, and leakage of cancer cells from the duct in the process of pancreatic fibrosis due to ductal obstruction. Expansive tumor growth in the pancreas was more vigorous the smaller the degree of fibrosis of the pancreas, and was most active where associated acute pancreatitis was seen or where the pancreas was X-irradiated one week before injection of carcinoma suspension.

Animals↗

Daily administration of the progesterone antagonist RU 486 prevents implantation in the cycling guinea pig.

Since progesterone is required to prepare the endometrium for implantation of an embryo, a progesterone antagonist may inhibit nidation and thus prevent pregnancy. We addressed this possibility in the guinea pig, the small laboratory animal whose reproductive physiology most resembles that of women. Daily administration of the antiprogestin RU 486 (0, 1, 2, or 3 mg/kg, subcutaneously) for 9 days after mating inhibited implantation in a dose-dependent fashion. When this compound was given daily throughout the estrous cycle, cyclic vaginal changes, ovulation, and mating were suppressed in up to 17%, 28%, and 55% of animals, respectively. Two of seven mated female animals receiving RU 486, 1 mg/kg/day, had implantation sites. Nidation was completely blocked at higher doses. Thus daily antiprogestin administration prevented pregnancy in sexually active, normally cycling guinea pigs. A similar strategy using a daily antinidatory dose of an antiprogestin may offer a novel approach to human fertility control.

Animals↗

Laparoscopy versus laparotomy for ovarian conservative surgery: a randomized trial in the rabbit model.

OBJECTIVE: Our purpose was to compare postoperative adhesion formation and reproductive outcome after the same ovarian surgical procedure performed by laparoscopy or laparotomy by means of microsurgical techniques. STUDY DESIGN: Twenty-eight New Zealand White female rabbits were randomly assigned to laparotomy or laparoscopy for the same standardized surgical procedure: both ovaries were grasped with atraumatic forceps and longitudinally incised on the antimesenteric side from the cortex to the hilum with a microelectrode delivering a tissue power density of 66,666 W/cm. The rabbits were then mated, and 2 weeks later a second-look laparotomy was performed by a blinded observer for the evaluation of postoperative adhesions, number of corpora lutea in each ovary, number of embryos in the ipsilateral uterine horn, and nidation index for each side. RESULTS: At second look no statistically significant differences were found in postoperative adhesion formation, number of corpora lutea, number of embryos, and nidation index between the laparoscopy and the laparotomy groups. CONCLUSION: Laparoscopy or laparotomy for ovarian conservative surgery do not appear significantly different in postoperative adhesion formation and reproductive outcome in the rabbit model.

Animals↗

Studies on the mechanisms of action of progesterone antagonists.

Antigestagens of RU-38.486-type were investigated in different pregnancy models reflecting either "endometrial" or "myometrial" effects. All antigestagens were found effective inhibitors of nidation in guinea pigs. This was evidence for a role of embryonic progesterone in the earliest events of nidation. No comparable inhibition could be obtained by ovariectomy. A more complex pharmacology was found around day 43 p.c. when the abortion was brought about by expulsion. RU-38.486 had marginal activity only. Antigestagens with reduced anti-glucocorticoid activity tended to induce abortions more effectively and faster. Some antigestagen-prostaglandin combinations were found of extreme abortifacient activity. Surprisingly it seemed that anti-glucocorticoid properties in addition to (or rather than) antigestagenic activities bring about this synergism with prostaglandin. The employed guinea pig model for pregnancy termination thus characterized two types of antigestagens: ideal ones for monotherapy or combined use with prostaglandin, respectively. Antigestagens induced a highly sensitive myometrium to prostaglandin-stimulation (Sulprostone) and a marked softening and dilatation of the cervix. Antigestagens perfectly prime the genital tract for oxytocic stimuli, they do not overcome the arrested uterine prostaglandin-secretion of the pregnant uterus at the same time.

Abortifacient Agents, Steroidal↗