Diagnosis and Management of ‘Cornual’ Pregnancies from 2002 to 2015 at a Tertiary Referral Centre in South India: Insights from Introspection

Purpose

Interstitial, angular and rudimentary horn pregnancies have all been referred to as cornual pregnancies despite definite diagnostic criteria. Angular pregnancies can be followed up expectantly under close surveillance while interstitial and rudimentary horn pregnancies are terminated by medical or surgical methods. This study aimed to assess accuracy of ultrasound in the diagnosis of ‘cornual pregnancy’ and evaluate management.

Methods

Data pertaining to clinical features, ultrasound findings and treatment modalities of the aforementioned conditions between January 2002 and December 2015 at a tertiary perinatal centre were retrieved from the medical records. The ultrasound images and surgical videos were reviewed by the authors.

Results

Of 62 cases, 35 were interstitial, 26 were angular/eccentric intrauterine, and 1 was a rudimentary horn pregnancy. The accuracy of ultrasonography in the diagnosis of interstitial and angular pregnancies was 71.0 and 46.8%, respectively. Medical management was successful in 33.3% of interstitial pregnancies. Fifteen women with interstitial pregnancy had subsequent pregnancies and nine (75.0%) were Caesarean deliveries. Rupture and recurrence rates of interstitial pregnancy were 34.2 and 2.9%, respectively. The rudimentary horn pregnancy was managed by laparoscopic excision followed by a subsequent term delivery.

Conclusion

This study identified frequent occurrences of imprecise nomenclature that resulted in mismanagement of a few potentially viable angular pregnancies. It is imperative for clinicians and sonologists to use unambiguous nomenclature and avoid the term ‘cornual pregnancy’ altogether.

     

Effect of intrauterine injection of human chorionic gonadotropin before fresh embryo transfer on IVF and ICSI outcomes: a meta-analysis

Purpose

This analysis was performed to evaluate the effects of intrauterine injection of human chorionic gonadotropin (hCG) before fresh embryo transfer (ET) on the outcomes of in vitro fertilization and intracytoplasmic sperm injection.

Methods

Randomized controlled trials (RCTs) were identified by searching electronic databases. The outcomes of live birth, clinical pregnancy, implantation, biochemical pregnancy, ongoing pregnancy, ectopic pregnancy, and miscarriage between groups with and without hCG injections were analyzed. Summary measures were reported as risk ratios (RR) with 95% confidence intervals.

Results

Six RCTs on fresh embryo transfer (ET) were included in the meta-analysis. A total of 2759 women undergoing fresh ET were enrolled (hCG group n?=?1429; control group n?=?1330). Intrauterine injection of hCG significantly increased rates of biochemical pregnancy (RR 1.61) and ongoing pregnancy (RR 1.58) compared to controls. However, there were no significant differences in clinical pregnancy (RR 1.11), implantation (RR 1.17), miscarriage (RR 0.91), ectopic (RR 1.65) or live birth rates (RR 1.13) between the hCG group and control group.

Conclusion

The current evidence for intrauterine injection of hCG before fresh ET does not support its use in an assisted reproduction cycle.

     

Heterotopic Quadruplet Pregnancy After ICSI Conception

Background

Heterotopic pregnancy (HP) is a condition characterized by the coexistence of multiple fetuses at two or more implantation sites. It occurs in 1% of pregnancies after assisted reproductive techniques (ART). Presence of triplet intrauterine pregnancy with ectopic gestational sac is one of the rarest forms of HP. Ectopic pregnancy is implanted in the ampullary segment of the fallopian tube in 80% of cases. Most of the patients present with acute abdominal symptoms due to rupture of the tube.

Case Presentation

This article reports a case of quadruplet heterotopic pregnancy after intracytoplasmic sperm injection (ICSI) with an ampullary ectopic pregnancy and intrauterine triplet pregnancies. The ruptured ampullary pregnancy was emergently managed by right salpingectomy. This was followed by embryo reduction at 12 + 6 weeks and successful outcome of intrauterine twin pregnancy.

     

Tubal restorative surgery for hydrosalpinges in women due to in vitro fertilization

Objective

The study was carried out to clarify the IVF outcome after laparoscopic neosalpingostomy for infertile patients affected by hydrosalpinx stage III. Materials and Methods: From January 2010 to June 2015, 91 subjects of hydrosalpinx stage III were treated in out center by laparoscopic surgery before IVF cycle. 43 underwent neosalpingostomy (group 1) and the remaining 48 underwent salpingestomy (group 2). We compared these patients and their IVF outcomes after two different surgical techniques.

Results

There were no significant differences between the two groups, except a higher number of patients with bilaterial hydrosalpinges was noted in the neosalpingostomy group (79.1% vs. 56.3%, respectively). 25 patients with neosalpingostomy and 29 with salpingectomy achieved pregnancy by IVF. The ongoing pregnancy rate per cycle in group 1 and group 2 was 51.1 and 47.2%, respectively. Two cases of ampullary ectopic pregnancies were noted in group 1 and one case of right tube interstitial pregnancy in group 2. No significant difference was observed in live birth rate between the groups (48.9% vs. 45.3%, respectively).

Conclusions

The outcomes of IVF after neosalpingostomy were matchable with salpingectomy. For patients desire to preserve fallopian tubes, we recommend laparoscopic neosalpingostomy as an alternative choice to manage moderate hydrosalpinx before IVF.

     

G-CSF and stem cell therapy for the treatment of refractory thin lining in assisted reproductive technology

Purpose

The study aims to describe two promising therapeutic options for resistant “thin” endometrium in fertility treatment: granulocyte colony-stimulating factor (G-CSF) and stem cell therapy.

Methods

A review of the scientific literature related to patients with thin endometrium undergoing fertility treatment.

Results

Sufficient endometrial growth is fundamental for embryo implantation. Whether idiopathic or resulting from an underlying pathology, a thin endometrium of <7 mm is associated with lower probability of pregnancy; however, no specific thickness excludes the occurrence of pregnancy. We specifically reviewed two relatively new treatment options for resistant thin lining: intrauterine G-CSF and stem cell therapy. The majority of the reviewed trials showed a significant benefit for intrauterine G-CSF infusion in improving endometrial thickness and pregnancy rates. Early results of stem cell therapy trials seem promising.

Conclusions

EMT <7 mm is linked to lower probability of pregnancy in assisted reproductive technology. Intrauterine G-CSF infusion appears to be a potentially successful treatment option for resistant cases, while stem cell therapy seems to be a promising new treatment modality in severely refractory cases.

     

Laparoscopic management of ectopic pregnancies: a comparison between interstitial and “more distal” tubal pregnancies

Background/aims

Laparoscopy is an established, safe, and feasible management option for tubal pregnancies, even in women with significant hemoperitoneum. In case of interstitial pregnancy, however, a laparoscopic surgical approach is still a matter of debate. The objective of this study is to evaluate the safety and feasibility of a laparoscopic approach to interstitial pregnancies.

Methods

A total of 92 women with ectopic pregnancy who underwent a surgical management from April 2009 to August 2015 were reviewed. Clinical and surgical outcomes of confirmed interstitial pregnancies (n = 10) (IP group) were compared with those of “more distal” tubal pregnancies (n = 79) (TP group).

Results

Although there were no differences between the two groups in gestational age, ß-hCG values were significantly higher in the IP group (p = 0.005). All patients with IP were treated by laparoscopic wedge resection. The rate of surgical complications (p = 0.413) and subsequent MTX treatment (p = 0.531) were not significantly different between groups. Operating room (OR) time (p = 0.007) was higher in the IP than in the TP group. After stratification for the presence of hemoperitoneum this difference remained, with patients in the IP group having longer OR time (p = 0.034) and additionally higher intra-operative blood loss (EBL) (p = 0.013). On the other hand, in the absence of hemoperitoneum no differences between the two groups were observed.

Conclusions

In experienced hands, the laparoscopic management of interstitial pregnancies seems to be as safe and feasible as that of other tubal pregnancies. However, it could be technically more challenging, especially in case of hemoperitoneum.

     

An Updated Review of Ectopic Pregnancies Resulting from Assisted Reproduction

Purpose of Review

The purpose of this study was to review the most recent data regarding clinical risk factors for ectopic pregnancy (EP) among patients pursuing assisted reproduction, and the diagnosis and management of EP in this specific population.

Recent Findings

EP rates following assisted reproduction have fallen over time to 1–2%, identical to the general population. Clinical risk factors for EP following assisted reproduction include the transfer of autologous, fresh and cleavage-stage embryos. Use of a GnRH agonist trigger alone for fresh cycles is associated with a greater risk of EP than hCG trigger. Serial hCG measurements and transvaginal ultrasound remain the mainstay of EP diagnosis. The addition of endometrial sampling to exclude failing intrauterine pregnancy spares a majority of patients unnecessary methotrexate. Two recent meta-analyses confirm that methotrexate for EP does not diminish subsequent response to controlled ovarian hyperstimulation (COH), while data conflict regarding the effects of salpingectomy on subsequent ovarian response. A recent randomized controlled trial, primarily in a non-infertility population, showed similar rates of subsequent intrauterine pregnancy following salpingectomy or salpingostomy in the presence of normal contralateral fallopian tubes. A large population-based study confirmed this finding, but reported higher ongoing pregnancy rates following tubal preservation in patients with infertility or tubal disease attempting natural conception.

Summary

The risk of EP following IVF appears largely mediated by altered endometrial receptivity, shown to result from COH and GnRH agonist-only triggers. Transfer of frozen-thawed blastocysts confers the lowest rate of EP following IVF. Methotrexate does not impact subsequent ovarian response to stimulation, though the effects of salpingectomy remain to be determined. Salpingectomy and salpingostomy confer equitable subsequent ongoing pregnancy rates, though tubal preservation may confer an advantage in women with tubal disease or infertility planning natural conception.

     

Cumulative pregnancy and live birth rates through assisted reproduction in women 44–45 years of age: is there any hope?

Purpose

The purpose of the study is to calculate the cumulative pregnancy rate and cumulative live birth rate in women undergoing in vitro fertilization (IVF) at ages 44–45.

Methods

The study calculated cumulative live pregnancy rate and cumulative live birth rate of 124 women aged 44 to 45 years old who commenced IVF treatment.

Main outcome measures

The main outcome measures are cumulative live pregnancy rate and cumulative live birth rate.

Results

Cumulative live pregnancy rates following 1, 2, 3, and 4 cycles were 5.6, 11, 17, and 20%, respectively, with no additional pregnancies in further cycles. Cumulative live birth rates following 1, 2, and 3 cycles were 1.6, 3, and 7%, respectively, with no additional live births in further cycles.

Conclusions

The cumulative pregnancy rate rises during the first 4 cycles and cumulative live birth rate rises during the first 3 cycles, with no additional rise in pregnancies or deliveries thereafter, suggesting that it is futile to offer more than 3 cycles of treatment to 44–45-year-old women.

     

Impact of surgery for endometriomas on pregnancy outcomes following in vitro fertilization-intracytoplasmic sperm injection. Who should be the preferred laparoscopists: gynecologists or reproductive surgeons?

Objective

To investigate whether laparoscopic excision of ovarian endometriomas pretreated with operation by gynecologists or reproductive surgeons exerts different effects on in vitro fertilization-intracytoplasmic sperm injection results.

Materials and methods

Retrospective case control study. Relevant information was collected from the electronic records of women who underwent IVF/ICSI from 01/01/2013 to 30/12/2015 in our unit. The study group consisted of 35 women who previously had laparoscopic endometrioma excision by reproductive surgeons in our unit; the control group included 36 patients who underwent surgery for endometriomas by gynecologists in our hospital.

Result(s)

There were slightly higher numbers of AFC and higher pregnancy rate in the study group, although differences did not reach statistical significance. For patients over 35 years old, there were more oocyte retrieved, mature oocytes and two pronucei (2PN) in the study group than the control group although observed differences did not reach statistical significance.

Conclusion(s)

Electrocautery is more deleterious on ovarian reserve than hemostatic suture. In procedure of patients who wish to conceive, surgeons should use hemostatic suturing technique preferentially.

     

Comparison of alternative βhCG follow-up protocols after single-dose methotrexate therapy for tubal ectopic pregnancy

Purpose

To evaluate the performances of five different βhCG follow-up protocols after single-dose methotrexate therapy for tubal ectopic pregnancy (EP).

Methods

Data of patients who received single-dose methotrexate therapy for tubal EP at a university hospital between January 2011 and July 2016 were reviewed. A ‘successful methotrexate treatment’ was defined if the EP treated with no need for surgery. The performances of different protocols were tested by comparing with the currently used ‘15% βhCG decrease between days 4 and 7’ protocol. The tested follow-up protocols were ‘20, 25%, and any βhCG decrease between days 0/1 and 7’ and ‘20% and any βhCG decrease between days 0/1 and 4’.

Results

Among the 96 patients evaluated, 12 (12.5%) required second dose. Totally, 91 (94.8%) patients treated successfully with no need for surgery. Four patients were operated within 4 days following the second dose. One patient who did not need second dose according to the standard follow-up protocol was operated on the 10th day due to rupture (specificity = 80%). Two protocols, namely ‘20% βhCG decrease between days 0/1 and 7’ and ‘any βhCG decrease between days 0/1 and 7’ did not show statistically significant differences from the index protocol regarding the number of patients who should be assigned to 2nd dose.

Conclusions

‘Any βhCG decrease between days 0/1 and 7’ protocol may substitute the currently used one to decide second dose methotrexate in tubal EP management. Omitting 4th day measurement seems to be more convenient and cost effective.

     

Progestin-Only Contraception and Bone Health

Purpose of Review

Progestin-only contraceptive methods are important and effective options for women trying to prevent unintended pregnancy. There is concern about progestin-only methods and bone health, particularly for depot medroxyprogesterone acetate (DMPA), because progestin-only methods can lower estradiol levels through ovarian suppression. This is of particular concern for adolescents building bone and perimenopausal women heading towards menopause.

Recent Findings

DMPA does cause temporary bone loss, but this is reversible after discontinuation. Evidence is limited as to whether the decreased bone density and subsequent reversal that is seen with DMPA use leads to an increased risk of fracture in the future. Two observational studies indicate a weak association between DMPA use and fracture risk. Progestin-only implants, pills, and the intrauterine device do not have an impact on bone mineral density or fracture risk.

Summary

Use of DMPA or any other progestin-only method should not be restricted due to a theoretical risk of fractures when reproductive-age women face the very real risk of pregnancy.

     

Clinical predictors of failing one dose of methotrexate for ectopic pregnancy after in vitro fertilization

Purpose

The aim of this study is to investigate the clinical predictors of failure of a single dose of methotrexate (MTX) for management of ectopic pregnancy after in vitro fertilization (IVF).

Methods

A retrospective cohort study was performed of women who conceived ectopic pregnancies following fresh or frozen IVF cycles at an academic infertility clinic between 2007 and 2014, and received intramuscular MTX (50 mg/m²). Successful single-dose MTX treatment was defined as a serum beta-human chorionic gonadotropin (hCG) decline ≥15% between days 4 and 7 post-treatment. Logistic regression models adjusted for oocyte age, number of embryos transferred, and prior ectopic pregnancy were used to estimate the adjusted odds ratio (OR) (95% confidence interval [CI]) of failing one dose of MTX.

Results

Sixty-four patients with ectopic pregnancies after IVF were included. Forty required only one dose of MTX (62.5%), while 15 required additional MTX alone (up to four total doses, 23.4%), and 9 required surgery (14.1%). By multivariable logistic regression, the highest tertiles of serum hCG at peak (≥499 IU/L, OR?=?9.73, CI 1.88–50.25) and at first MTX administration (≥342 IU/L, OR?=?4.74, CI 1.11–20.26), fewer embryos transferred (OR?=?0.37 per each additional embryo transferred, CI 0.19–0.74), and adnexal mass by ultrasound (OR?=?3.65, CI 1.10–12.11) were each correlated with greater odds of requiring additional MTX and/or surgery.

Conclusion

This is the first study to report that in women with ectopic pregnancies after IVF, higher hCG—though well below treatment failure thresholds previously described in spontaneous pregnancies—fewer embryos transferred, and adnexal masses are associated with greater odds of failing one dose of MTX. These findings can be used to counsel IVF patients regarding the likelihood of success with single-dose MTX.

     

Pregnancy after endometrial scratching in infertile couples undergoing ovulation induction and intrauterine insemination cycles—a randomized controlled trial

Purpose

To study the effect of endometrial scratching in infertile couples undergoing ovulation induction and intrauterine insemination (IUI) cycles.

Methods

A prospective randomized controlled trial was conducted in the Department of Obstetrics and Gynaecology, AIIMS, New Delhi, India. One hundred forty-four women with primary/secondary infertility were recruited. Couples were either unexplained or male factor infertility. Subjects were randomized into intervention (scratching) and control group. All patients received ovulation induction with clomiphene citrate (day 2–6) 50 mg/day +75 IU HMG on days 6 and 7. In addition, endometrial scratching was done on day 8 of ovulation induction cycle in intervention group. All couples were planned for three cycles of ovulation induction and IUI over 6 months. After each failed cycle, couple was advised to try for natural conception for one cycle. Those who conceived were excluded from further analysis. Primary outcome was clinical pregnancy rate. Secondary outcome measures included conception rate, ongoing pregnancy, abortion and ectopic rate.

Results

Baseline characteristics were comparable in both groups. Clinical pregnancy rate was significantly higher in intervention group (31.9%; 23/72) as compared to control group (16.7%; 12/72) (p value 0.030). On per cycle analysis, first IUI cycle had significantly high pregnancy rate (18.1%; 13/72) as compared to control group (5.6%; 4/72). Three patients in intervention group and one in control group conceived in wash out cycle. Ongoing pregnancy rate was significantly higher in scratching group (30.0%; 21/70) as compared to control group (15.7%; 11/70) (p value0.044).

Conclusions

Endometrial scratching can be used as a low cost-effective tool to improve clinical pregnancy and ongoing pregnancy rate in IUI cycles. Further large number studies are required to document its role in improving live birth rate.

Trial registration number

CTRI/2015/12/006419

     

Methotrexate does not affect ovarian reserve or subsequent assisted reproductive technology outcomes

Purpose

The purpose of this research was to study whether methotrexate (MTX) as treatment for ectopic pregnancy (EP) impacts the future fertility of women undergoing assisted reproductive technology (ART)

Methods

In a systematic review and multi-center retrospective cohort from four academic and private fertility centers, 214 women underwent an ART cycle before and after receiving MTX as treatment for an EP. Measures of ovarian reserve and responsiveness and rates of clinical pregnancy (CP) and live birth (LB) were compared in the ART cycles prior and subsequent to MTX.

Results

Seven studies were identified in the systematic review, and primary data from four institutions was included in the final analysis. Women were significantly older in post-MTX cycles (35.3 vs 34.7 years). There were no differences in follicle stimulating hormone, antral follicle count, duration of stimulation, oocytes retrieved, or fertilization rate between pre- and post-MTX cycles. However, post-MTX cycles received a significantly higher total dose of gonadotropins (4206 vs 3961 IU). Overall, 42 % of women achieved a CP and 35 % achieved a LB in the post-MTX ART cycle, which is similar to national statistics. Although no factors were identified that were predictive of LB in young women, the number of oocytes retrieved in the previous ART cycle and current AFC were predictive of LB (AUC 0.76, 0.75) for the older women.

Conclusions

MTX does not influence ovarian reserve, response to gonadotropin stimulation, and CP or LB rate after ART. MTX remains a safe and effective treatment option for women with asymptomatic EPs.

     

Fertility outcome after treatment of retained products of conception: a systematic review

Background

Treatment of retained products of conception (RPOC) can be expectant, medical or operative. Surgical removal of RPOC may lead to intrauterine adhesions (IUA) and Asherman’s syndrome.

Objective

To evaluate how treatment options for RPOC affect future fertility by means of a systematic review.

Search strategy

MEDLINE, EMBASE, The Cochrane Library, and clinical trial registers were searched, and reference lists were scanned.

Selection criteria

Randomised controlled trials (RCT) comparing different treatment options for RPOC (conservative, medical or surgical treatment, including curettage and/or hysteroscopic techniques, with or without application of anti-adhesion therapy), in women of reproductive age, were eligible for inclusion.

Data collection and analysis

Reviewers independently performed data extraction and quality of evidence assessment. For dichotomous variables, results were presented as risk ratio (RR) with 95% CI.

Main results

Two studies were included. Nonsignificant differences were observed between the use of an anti-adhesion barrier gel versus no treatment after operative hysteroscopy in IUAs (RR 0.32, 95% CI 0.04 to 2.80, P value?=?0.30) and clinical pregnancy (RR 2.22, 95% CI 0.67 to 7.42, P value?=?0.19), and between hysteroscopic morcellation versus loop resection in IUAs (RR 0.86, 95% CI 0.06 to 13.12, P value?=?0.91).

Conclusion

There is insufficient evidence on how different treatment options for RPOC affect future reproductive outcomes. Results from ongoing RCTs are needed to guide clinicians towards choosing the best treatment.

     

Expectant management may reduce overtreatment in women affected by unexplained infertility confirmed by diagnostic laparoscopy

Purpose

To determine whether the mini-invasive surgery still play a role in the diagnostic workup and in the management of the couples affected by unexplained infertility.

Methods

170 infertile women (age range 25–38 years) with documented normal ovarian, tubal and uterine function underwent combined hysteroscopic and laparoscopic surgery; 100 women refused surgery or ART treatment (control group) choosing expectant management. A retrospective assessment questionnaire was proposed to enrolled women to collect the rate of spontaneous or ART-induced pregnancies.

Results

The combined surgery revealed pelvic pathologies in 49.4% of patients, confirming the diagnosis of unexplained infertility only in 86 of studied patients. In this group of 86 selected women, 28 of them achieved a spontaneous pregnancy and 23 women obtained pregnancy after ART. The Chi-square analysis shows that the pregnancy rate was not influenced by the employment of ART. In the group of 100 control women, only 14 (14%) achieved a spontaneous pregnancy after 18 months of expectant management.

Conclusions

Combined laparoscopy and hysteroscopy in women with unexplained infertility may reveal previously undiagnosed pathologies that could require ART, and in those without abnormal surgical finding, ART does not improve pregnancy rate.

     

Chronic Endometritis and Recurrent Pregnancy Loss

Purpose of Review

Chronic endometritis is generally an asymptomatic condition typically diagnosed by the histopathological presence of plasma cell infiltration in the endometrial stromal compartment. Emerging data suggests that chronic endometritis may be a cause of recurrent pregnancy loss (RPL).

Recent Findings

Chronic endometritis is prevalent in cases of otherwise unexplained recurrent pregnancy loss. Treatment appears to lead to improved pregnancy outcomes in subsequent pregnancies. The use of CD138 immunohistochemistry as a supplement to traditional hematoxylin and eosin staining of plasma cells increases the detection rate of chronic endometritis.

Summary

Chronic endometritis is emerging as a treatable cause of RPL.

     

Ovarian hyperstimulation syndrome following GnRH agonist trigger—think ectopic

Purpose

This study aims to report a case of ovarian hyperstimulation syndrome (OHSS) following GnRH agonist trigger for final follicular maturation.

Methods

This study is a retrospective chart review.

Results

We report the first case of OHSS following GnRH agonist trigger for final follicular maturation and freeze-all, masking extrauterine pregnancy (EUP). The present case report elucidates the feasibility of stimulating and recruiting ovarian follicles yielding mature oocytes during early pregnancy and the ability of GnRH agonist to trigger final follicular maturation during pregnancy, in the presence of high progesterone and hCG levels.

Conclusions

Since OHSS almost always develops after hCG administration or in early pregnancy, its occurrence following GnRH agonist trigger should alert physician to search for either an inadvertent administration of exogenous hCG, or the endogenous secretion of hCG by pregnancy, e.g. EUP, or as part of a paraneoplastic syndrome.