Short-term Reproductive Outcomes of Nulliparous Women with Previous Ectopic Pregnancy.

OBJECTIVE: To determine the characteristics and subsequent pregnancy outcomes in patients with a previous ectopic pregnancy (EP). STUDY DESIGN: Descriptive-cross sectional study. PLACE AND DURATION OF STUDY: Department of Obstetrics-Gynaecology, Etlik Zubeyde Hanim Maternity and Women's Health Teaching and Research Hospital, Ankara, Turkey, between January 2014 and December December 2018. METHODOLOGY: The data of nulliparous patients diagnosed with tubal ectopic pregnancy (EP) was analysed retrospectively. Reproductive outcomes within the first two years after ectopic pregnancy diagnosis were used as "short-term" reproductive outcomes. Their EP treatment and pregnancy outcome were determined. RESULTS: Expectant management was chosen in 5.8% of the patients, while the surgical intervention was 32.3%. Medical therapy involving methotrexate (MTX) was given to the remaining patients (61.9%). The tubal rupture was confirmed in 12% of the cases that received MTX. In the 2-year follow-up period after the ectopic event, the most common outcome of the subsequent pregnancies was a live birth (47.7%). Recurrent EP occurred in 4.6%. CONCLUSION: The subsequent short-term pregnancy outcomes in this study were not related to the chosen treatment modality. KEY WORDS: Ectopic pregnancy, Nulliparity, Reproductive outcomes, Treatment modalities, Expectant management.

TRPV4 is involved in levonorgestrel-induced reduction in oviduct ciliary beating.

Previous studies revealed the increasing risk of tubal pregnancy following failure of levonorgestrel (LNG)-induced emergency contraception, which was attributed to the reduced ciliary motility in response to LNG. However, understanding of the mechanism of LNG-induced reduction in the ciliary beat frequency (CBF) is limited. The transient receptor potential vanilloid (TRPV) 4 channel is located widely in the female reproductive tract and generates an influx of Ca2+ following its activation under normal physiological conditions, which regulates the CBF. The present study aimed to explore whether LNG reduced the CBF in the Fallopian tubes by modulating TRPV4 channels, leading to embryo retention in the Fallopian tubes and subsequent tubal pregnancy. The study provided evidence that the expression of TRPV4 was downregulated in the Fallopian tubes among patients with tubal pregnancy and negatively correlated with the serum level of progesterone. LNG downregulated the expression of TRPV4, limiting the calcium influx to reduce the CBF in mouse oviducts. Furthermore, the distribution of ciliated cells and the morphology of cilia did not change following the administration of LNG. LNG-induced reduction in the CBF and embryo retention in the Fallopian tubes and in mouse oviducts were partially reversed by the progesterone receptor antagonist RU486 or the TRPV4 agonist 4α-phorbol 12,13-didecanoate (4α-PDD). The results indicated that LNG could downregulate the expression of TRPV4 to reduce the CBF in both humans and mice, suggesting the possible mechanism of tubal pregnancy. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Bilateral ampulary pregnancy after clomifen citrate and intrauterine insemination--a unique case report.

We report a case with bilateral tubal ampullary pregnancy after Clomifen Citrate medication. The first conception in the right tube was after intrauterine insemination or intercourse performed before insemination, while the second one was achieved 10 d after insemination, during the intercourse, in the left tube. This life-threatening and routinely unexpected finding must always have in mind all doctors dealing with patients in emergency care, especially those receiving fertility enhancing drugs. According to the literature data available, this is the first and unique such case in the literature.

Simultaneous presentation of tubal and primary abdominal pregnancies following clomiphene citrate treatment.

Abdominal pregnancy is a rare condition that is potentially life-threatening for the mother. We present a case of simultaneous ectopic pregnancies (EPs) in the right fallopian tube and in the vesicouterine pouch. A 26-year-old woman had undergone prior ovulation induction with clomiphene citrate and human chorionic gonadotropin (hCG) at an outside hospital for unexplained infertility. The patient was referred to our hospital for a suspected ectopic pregnancy at 6 weeks gestation. Transvaginal ultrasonography detected a viable fetus at the anterior left side of the uterus; therefore, we suspected a left tubal pregnancy. However, laparoscopic surgery revealed that EPs were located in both the left vesicouterine pouch and in the right fallopian tube. Resection of the right salpinx and abdominal implant were performed. Histopathological examination confirmed the simultaneous presentation of a primary abdominal pregnancy and a right tubal pregnancy. After surgery, the patient's serum hCG level returned to normal. Concurrent EPs and abdominal pregnancy are very rare. However, it should be noted that reproductive technologies sometimes cause unusual clinical situations. A thorough abdominal inspection is needed.

Bilateral simultaneous isthmic ectopic pregnancy after clomiphene induction.

A rare case of a 32-year-old patient with simultaneous bilateral isthmic tubal pregnancy. A 32-year-old woman with a 3-year history of primary infertility was admitted with light vaginal bleeding and mild abdominal pain. She was 41 days after her last menstruation and 23 day after intrauterine insemination with her husband's sperm. Clomiphene citrate (CC) was used for the induction of ovulation. In cases of ectopic pregnancy with ovulation induced by CC, doctors must be aware of the possibility of bilaterality.

Clomiphene citrate causes aberrant tubal apoptosis and estrogen receptor activation in rat fallopian tube: implications for tubal ectopic pregnancy.

Clomiphene citrate (CC) therapy for disorders of anovulatory infertility has been linked to an increased frequency of tubal ectopic pregnancy. Although CC enhances apoptotic processes in the ovaries, villi, and decidual tissues, its effect on apoptosis in the fallopian tube is unknown. Here, we show that chronic treatment with CC induces tubal apoptosis, but not necrosis, through an intrinsic mitochondria-dependent signaling pathway in vivo. The apoptosis was specific to epithelial cells in the isthmus, and the damage was reversed with 17beta-estradiol (E2); however, pretreatment or concomitant treatment with E2 did not protect against tubal apoptosis induced by chronic treatment with CC. Chronic treatment activated estrogen receptors (ESRs), particularly cilia-localized ESR2A (formerly ERbeta2). In contrast to E2, acute treatment of superovulating rats with a high dose of CC or the ESR2-selective agonist 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN) significantly delayed the transport of oocyte-cumulus complexes through the fallopian tube. Our findings suggest that in response to chronic CC therapy, isthmus-specific apoptosis of epithelial cells and activation of cilia-ESR2A act in parallel to block gamete and embryo passage through the fallopian tube, eventually resulting in tubal ectopic pregnancy.

Ectopic pregnancy following levonorgestrel emergency contraception: a case report.

Use of levonorgestrel as emergency contraception is a safe and effective measure to prevent unwanted pregnancy. However, ectopic gestation in case of failure is a known risk. Access to levonorgestrel without a prescription in many countries has made it impossible to estimate the exact incidence of this potential adverse event. Thus, spontaneous reporting of cases serves to alert physicians to this possibility. We present a case of ectopic pregnancy following use of levonorgestrel emergency contraception. To our knowledge, this is the first case report from India following introduction of levonorgestrel emergency contraception in 2001.

[Heterotopic pregnancy following ovulation induction by clomiphene citrate and prednisone. Report of a case]. / Embarazo heterotópico, después de inducción de ovulación con citrato de clomifeno y prednisona. Informe de un caso.

Heterotopic pregnancy (HP) is a very rare pathologic event. The incidence of ectopic pregnancy has increased as the consequence of assisted reproduction and the wider use of ovulation induction agents. The diagnosis of HP is frequently done not as earlier as it should be, and it has serious repercussions. The concept of screening, to find relevant rise factors and the correct diagnosis of HP should be pursued as early as possible. In this report we describe an unusual case of a female patient with therapeutic failure to clomiphene citrate. She was treated with two cycles of combined clomiphene citrate and prednisone, and ovulation induction assent. The after she developed HP. Overall, we conclude that the possible association observed could be an accident. The land of investigation is open, to fill cover. The holes on understanding that we still have.

[Extrauterine pregnancy after hormonal postcoital contraception]. / Extrauteringraviditäten nach hormoneller Postkoitalkontrazeption.

Postcoital contraception with estrogen-gestagen-combinations is a highly effective emergency measure in cases of unprotected sexual intercourse at midcycle. Pregnancies after hormonal postcoital contraception are rare and ectopic pregnancies are said to be an extreme rarity. At the Department of Obstetrics and Gynecology of the Philipps-University Marburg we could observe two women with ectopic pregnancies after administration of a ethinyestradiol-levonorgestrel combination (Tetragynon, Schering, Berlin). Both patients were operated by pelviscopy. We could not found a clear causal relationship between the administration of hormonal postcoital contraception and ectopic pregnancies, because both women had intrauterine operations in her history and therefore a certain level of tubal damage could not ruled out. Nevertheless, in cases of hormonal postcoital contraception a follow-up check after 3 weeks should be done and it should be kept in mind that ectopic pregnancies may occur, especially in patients with risk factors.

[Clomifene -induced bilateral simultaneous tubal pregnancy]. / Clomifeninduzierte bilaterale simultane Tubargravidität.

A case of a clomifen induced bilateral simultaneous tubal pregnancy after micro-surgical tubal operation is reported. Causes, diagnostics, therapy, and possible preventions are discussed on the basis of current literature.

[Ovarian stimulation with clomiphene is not a risk factor for extrauterine pregnancy]. / Die ovarielle Stimulation mit Clomifen stellt keinen Risikofaktor für eine Extrauteringravidität dar.

In a retrospective cohort study of 252 patients with ectopic pregnancies the possible association between use of clomiphene citrate and the occurrence of an ectopic pregnancy was examined. Seventeen out of 252 patients had been treated with clomiphene. Epidemiologic data and animal experiments suggest, that there may be a role of clomiphene in the etiology of ectopic pregnancy. Marchbanks et al. [6] reported that patients who used clomiphene were found to have a relative risk of 10.0 for ectopic pregnancy. The analysis of our own data show an accumulation of classic risk factors as history of pelvic inflammatory disease or of microsurgery for treatment of tubal disease in the clomiphene group. The higher rate of ectopic pregnancies in patients who have been treated with clomiphene is more likely associated with the diagnosis of infertility than with the use of ovulatory-inducing agents. Clomiphene treatment is no independent risk factor in the etiology of ectopic pregnancy.

Simultaneous intra- and extrauterine pregnancy after multiple ovulation induction.

Superovulation was induced by combined treatment with a GnRH analog, hMG and hCG in a 31 years old nulligravida with a diagnosis of unexplained infertility. She developed a mild hyperstimulation syndrome for which she received conservative treatment in hospital, and she was discharged only after we demonstrated a gestation sac in utero with evident fetal heart beat and beta hCG assays were positive. One week later the patient was readmitted urgently with acute abdominal pain. Laparoscopy revealed a left tubal pregnancy with corpus luteum on the right ovary and free blood in the pouch of Douglas. Salpingotomy was therefore performed with dilatation and curettage of the uterine cavity. Histological examination confirmed the presence of contemporary intra- and extrauterine pregnancy. Based on this first communication, a high index of clinical suspicion for an extrauterine pregnancy is warranted in all patients undergoing superovulation even after a pregnancy in utero has been demonstrated.