Reproductive outcome after letrozole versus laparoscopic ovarian drilling for clomiphene-resistant polycystic ovary syndrome

Objective

To compare the clinical outcomes of letrozole and laparoscopic ovarian drilling (LOD) in patients with clomiphene-citrate-resistant polycystic ovary syndrome (PCOS).

Methods

In the present prospective randomized trial, 140 women with clomiphene-citrate-resistant PCOS were randomly allocated to receive 5 mg letrozole from day 3 to day 7 of menses for 6 consecutive cycles, or to undergo LOD. When a leading follicle of at least 18 mm was present, ovulation was triggered with human chorionic gonadotropin (hCG). The 6-month rates of ovulation, pregnancy, abortion, and live births were evaluated.

Results

The groups were similar with regard to baseline clinical characteristics and hormonal profiles. The ovulation rate was significantly higher in the letrozole group than in the LOD group (59.0% versus 47.5%). On the days of the hCG injection, women in the letrozole group had a significantly thicker endometrium than those in the LOD group (P < 0.0001). Women receiving letrozole had a higher pregnancy rate (35.7% versus 28.6%) and a lower rate of spontaneous abortion (8.0% versus 20.0%, respectively), but these differences were not statistically significant.

Conclusion

Letrozole seems to be a suitable second-line ovulation-inducing alternative to LOD in women with PCOS who do not conceive with clomiphene citrate.     

Short-term metformin treatment for clomiphene citrate-resistant women with polycystic ovary syndrome

Objective

To evaluate the effect of a short-course pretreatment with metformin on hyperandrogenism, insulin resistance, cervical scores, and pregnancy rates in women with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS).

Methods

Thirty-seven women with CC-resistant PCOS were randomly assigned to be pretreated with 500 mg of metformin or placebo 3 times per day for 2 cycles, and 100 mg of CC was given on days 5 through 9 of the second cycle in both groups. Luteinizing hormone (LH), follicle stimulating hormone (FSH), dehydroepiandrostendione sulfate (DHEAS), total testosterone (T), glucose, and insulin levels were measured at baseline and after the first cycle, as well as body mass index (BMI), cervical score, and pregnancy rate.

Results

After 1 cycle, BMI, total T level, and percentage of participants with insulin resistance were significantly decreased in the metformin group, without any significant decrease in LH, FSH, and DHEAS levels; and in the second cycle, CC treatment resulted in a higher ovulation rate and a thicker endometrium in the metformin group. The pregnancy rate and cervical scores were also higher in that group.

Conclusion

The short-course pretreatment with metformin decreased hyperandrogenism and insulin resistance and improved cervical sores, ovulation rate, and pregnancy rate among women with CC-resistant PCOS.     

The administration of metformin during pregnancy reduces polycystic ovary syndrome related gestational complications

Objectives

To prospectively evaluate the safety of metformin administration during pregnancy in a group of PCOS patients by assessing its effect on the prevalence of gestational complications and neonatal outcome.

Study design

Our prospective, single centre study included 98 pregnant women with PCOS treated with metformin throughout pregnancy and 110 normal pregnant controls. All PCOS patients were hyperinsulinemic and received metformin (1700-3000 mg/day) before conception and until 37 weeks’ gestation.

Results

Metformin treatment in the pregnant PCOS patients resulted in significant decrease in miscarriage rate (9.1% vs 20%; p < 0.05), gestational diabetes (0 vs 13%; p < 0.005), and gestational hypertension (0 vs 11%; p < 0.005) and a non-significant decrease in pre-eclampsia (0 vs 3%; p = .24), compared to the control group. Mean neonatal Apgar score, weight and length were comparable between the two groups.

Conclusions

Continuing metformin therapy throughout pregnancy resulted in significant reduction in pregnancy complications with concomitant improved neonatal outcome, with no serious deleterious side effects.     

Metformin versus laparoscopic ovarian drilling in clomiphene- and insulin-resistant women with polycystic ovary syndrome

Objective

To compare the hormonal-metabolic profiles and reproductive outcomes in clomiphene-resistant patients with polycystic ovary syndrome and insulin resistance between women receiving metformin and those undergoing laparoscopic ovarian drilling.

Methods

A total of 110 eligible participants were randomly allocated to diagnostic laparoscopy plus metformin therapy (group 1, n = 55) or laparoscopic ovarian drilling (group 2, n = 55). The t test was used for mean comparisons of hormonal-metabolic parameters and OGTT values before and after treatment. The χ² test was used for comparisons of ovulation, pregnancy, and abortion rates.

Results

Groups 1 and 2 showed a significant decline in testosterone, insulin-like growth factor-1 (P < 0.001 vs P < 0.001), and luteinizing hormone (P < 0.05 vs P < 0.001), while the glucose to insulin ratio was significantly increased (P < 0.001 vs P < 0.05) compared with baseline. Group 2 patients had more regular cycles and higher rates of ovulation and pregnancy compared with group 1: 76.4% [42/55] vs 58.2% [32/55], P < 0.04; 50.8% [131/258] vs 33.5% [94/281], P < 0.001; and 38.2% [21/55] vs 20.0% [11/55], P < 0.03, respectively. The difference in the early abortion rate between the groups was not statistically significant.

Conclusion

Although metformin results in a better attenuation of insulin resistance, laparoscopic ovarian drilling is associated with higher rates of ovulation and pregnancy.     

Use of traditional Chinese medicine among pregnant women in Taiwan

Objective

To investigate the patterns of traditional Chinese medicine (TCM) use among pregnant women in the National Health Insurance program in Taiwan.

Methods

Women who gave birth in Taiwan in 2006 were identified from the National Health Insurance Research Database. Claims for reimbursement following TCM ambulatory visits by these women were analyzed.

Results

In total, 20.9% of women in the study who gave birth in 2006 used TCM during pregnancy, with older women more likely to utilize this form of care (23.9% of women > 35 years of age vs 16.2% of women < 20 years of age). There was an increase in the use of TCM for pregnancy-related problems such as hypertension (194 women before pregnancy vs 2163 during) and nausea/vomiting (220 women before vs 1648 during). The predominant modality (88.4%) of TCM treatment during pregnancy was herbal preparation.

Conclusion

Traditional Chinese medicine, with the exception of acupuncture, is popular among pregnant women in Taiwan. In addition to its efficacy, the safety of TCM during pregnancy requires future investigation.     

Effect of laparoscopic ovarian drilling on vascular endothelial growth factor and ovarian stromal blood flow using 3-dimensional power Doppler

Objective

To determine, by using 3-dimensional power Doppler ultrasonography, the effect of laparoscopic ovarian drilling (LOD) on the serum level of vascular endothelial growth factor (VEGF) and ovarian stromal blood flow changes in polycystic ovary syndrome (PCOS).

Methods

A prospective controlled clinical study was conducted on 26 clomiphene-resistant women with PCOS who were scheduled for LOD and a control group of 22 fertile regularly menstruating women. VEGF and 3 ovarian Doppler indices—vascularization index, flow index, and vascularization flow index—were measured and compared between the 2 groups, and before and after LOD in the PCOS group.

Results

Serum VEGF and the Doppler indices of ovarian stromal blood flow were significantly higher in the PCOS group than in the control group. Serum VEGF and the ovarian stromal blood flow Doppler indices were significantly reduced in the PCOS group after LOD.

Conclusion

Increased vascularity in PCOS demonstrated by Doppler blood flow measurements might be explained by the high level of VEGF. LOD reduced ovarian vascularization and serum VEGF.     

Management guidelines for obstetric patients and neonates born to mothers with suspected or probable severe acute respiratory syndrome (SARS) : No. 225, April 2009

Objective

This document summarizes the limited experience of SARS in pregnancy and suggests guidelines for management.

Outcomes

Cases reported from Asia suggest that maternal and fetal outcomes are worsened by SARS during pregnancy.

Evidence

Medline was searched for relevant articles published in English from 2000 to 2007. Case reports were reviewed and expert opinion sought.

Values

Recommendations were made according to the guidelines developed by the Canadian Task Force on Preventive Health Care.     

Sexuality and psychological wellbeing in women with polycystic ovary syndrome compared with healthy controls

Objectives

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of fertile age. The aim was to study whether PCOS has an effect on sexual functioning.

Study design

Women meeting the Rotterdam criteria for PCOS (n = 49), and 49 age-matched controls identified from the population registry, were recruited. Sexual functioning was assessed by means of (i) an in-person, structured interview covering various aspects of sexuality, and (ii) the nine-item McCoy questionnaire of female sexual satisfaction. Participants also completed the Psychological General Well-Being Index.

Results

Almost half the women with PCOS reported that the disorder had a great impact on their sex life. Despite having the same number of partners and about the same frequency of sexual intercourse, women with PCOS were generally less satisfied with their sex lives compared to the population-based controls. Within the group of women with PCOS, high body mass index had only a minor effect on sexual functioning, while the total serum level of testosterone correlated positively to sexual satisfaction. PCOS women scored numerically lower than controls on the McCoy total score, but this difference was not statistically significant.

Conclusion

Women with PCOS reported decreased satisfaction with their sex life. Sexual function should be taken into account in treatment trials of PCOS, which traditionally target only symptoms related to insulin resistance, overweight, and hirsutism.     

Ovulation Induction in Polycystic Ovary Syndrome : No. 242, May 2010

Objective

To review current non-pharmacologic and pharmacologic options for ovulation induction in women with polycystic ovary syndrome (PCOS).

Options

This guideline reviews the evidence for the various options for ovulation induction in PCOS.

Outcomes

Ovulation, pregnancy and live birth rates, risks, and side effects are the outcomes of interest.

Evidence

Published literature was retrieved through searches of Medline using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Grey (unpublished) literature was identified through searching the websites of health technology assessment and of health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

Values

The evidence gathered was reviewed and evaluated by the Reproductive Endocrinology and Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada. The quality of evidence was quantified using the Canadian Task Force on Preventive Health Care.

Benefits, Harms, and Costs

Benefits include weight reduction and improvements in ovulation, pregnancy, and live birth rates. Potential harms include medication side effects and multiple pregnancies.

Validation

These guidelines have been reviewed and approved by the Reproductive Endocrinology and Infertility Committee of the SOGC.

Sponsor

The Society of Obstetricians and Gynaecologists of Canada.     

Clomiphene citrate versus tamoxifen for ovulation induction in women with PCOS: a prospective randomized trial

Objective

To reevaluate the efficacy of induction of ovulation with CC versus TMX in a group of anovulatory subfertile women with PCOS in a randomized controlled trial.

Study design

A prospective randomized controlled study in which 371 PCOS patients were randomly allocated into two treatment groups: group A (187 patients) where women received CC and group B (184 patients) where they received Tamoxifen for one treatment cycle. The outcome measures were number of growing and mature follicles, serum E₂ (pg/ml), serum progesterone (ng/ml) and endometrial thickness, the occurrence of pregnancy and miscarriage.

Results

The number of stimulated follicles reaching ≥16 mm diameter was significantly more in the CC group compared to Tamoxifen stimulated group (2.1 SD ± 0.1 vs. 1.1 SD ± 0.7, p < 0.0001). The endometrium at the time of hCG administration was significantly thicker in the TMX group (10.1 ± 0.1 mm vs. 9.3 ± 0.4 mm, p < 0.0001). Ovulation occurred in 120/187 cycles (64%) in the CC group and 95/184 cycles (51.6%) in the TMX group with a significant difference between two groups in favors of clomiphene (p = 0.01). Serum E₂, on the day of hCG administration, was significantly higher in the clomiphene group (p < 0.0001). Pregnancy occurred in 35/187 cycles in group A (18.7%) and 20/184 cycles (10.8%) in group B and the difference was statistically significant (p = 0.04).

Conclusions

Clomiphene citrate is more successful than tamoxifen as a first line therapy for ovulation induction in women with PCOS.     

Twelve-year experience with laparoscopic radical hysterectomy and pelvic lymphadenectomy in cervical cancer

Objectives

This study aims to evaluate the morbidity, oncological outcome, and prognostic factors of cervical cancer patients treated with laparoscopic radical hysterectomy and pelvic lymphadenectomy (LRH).

Methods

Patients with cervical cancer undergoing LRH at the First People's Hospital of Foshan between August 1998 and March 2010 were enrolled in this study. The medical records were reviewed.

Results

A total of 240 patients were identified. According to FIGO stage, the number of patients with stage Ia2, Ib1, Ib2, IIa, and IIb was 2, 163, 34, 35, and 6, respectively. The conversion rate was 1.25%. Intraoperative and postoperative complications occurred in 7.08% and 9.16% patients, respectively. Other medical problems included 74 cases (30%) of bladder dysfunction. Excluding the lost cases, the median follow-up of 221 cases was 35 months, and 5-year survival rate for Ia2, Ib1, Ib2, IIa was 100%, 82%, 66%, 60%, respectively. Univariate analysis showed factors impacting the survival rate were FIGO stage > Ib1, non-squamous histologic type, deep cervical stromal invasion, and lymph node metastasis (P = 0.027, 0.023, 0.007, 0.000). The Cox-proportional hazards regression analysis indicated that only lymph node metastasis (OR = 3.827, P = 0.000) was independent of poor prognostic factor. The 5-year survival rates in Ib1 were 88% with negative lymph nodes and 59% with positive lymph nodes (P = 0.000).

Conclusions

Our data demonstrate that LRH can be performed in stage Ia2-Ib1 or less advanced node negative cervical cancer patients without compromising survival. The feasibility of LRH for more advanced patients needs further investigations.     

The rapid biophysical profile for early intrapartum fetal well-being assessment

Objective

To determine the efficacy of the rapid biophysical profile (rBPP), which uses sound-provoked, ultrasonographically detected fetal movement and amniotic fluid index, for early intrapartum fetal well-being assessment and prediction of adverse perinatal outcomes.

Methods

Rapid BPP was performed in 330 women admitted to the labor unit of Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand, from January 2005 to July 2005. Those who were delivered later than 24 h after the rBPP, or who required emergency cesarean section because of placenta previa, abruptio placentae or prolapsed cord were to be excluded. Perinatal outcomes were prospectively assessed and recorded for subsequent analysis. The predicting accuracy of rBPP was calculated according to poor outcomes, which included fetal distress, low Apgar score, admission to the neonatal intensive care unit and perinatal death.

Results

Among the 330 pregnancies, there were 6 adverse perinatal outcomes (1.8%). The rBPP had a sensitivity of 50.0%, a specificity of 99.07%, a positive predictive value of 50.0%, a negative predictive value of 99.07% and an accuracy of 98.18%.

Conclusion

With its simplicity, low cost and high specificity but its low sensitivity and low negative predictive value, the rBPP may be used as a back-up test to confirm fetal well-being during the early intrapartum period in developing countries.     

Three-dimensional power Doppler imaging in the diagnosis of polycystic ovary syndrome

Objective

To determine the role of three-dimensional (3D) power Doppler imaging in the diagnosis of polycystic ovary syndrome (PCOS).

Methods

Pulsatility index (PI) and resistance index (RI) of the uterine artery and ovary were measured by two-dimensional (2D) Doppler imaging, while vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured by 3D power Doppler in 25 patients with PCOS and 25 women with normal menstrual cycles used as a control group.

Results

Uterine artery PI and RI were significantly higher (P < 0.001) and ovarian PI and RI were significantly lower (P < 0.001) in women with PCOS compared with controls. Ovarian VI and VFI were significantly higher in women with PCOS compared with the control group (P < 0.001).

Conclusion

3D power Doppler indices were higher in women with PCOS than in the control group and were positively correlated with 2D color Doppler indices, and clinical and hormonal parameters. High 3D power Doppler indices may be useful as one of the diagnostic criteria for PCOS.     

A phase II evaluation of trabectedin in the treatment of advanced, persistent, or recurrent uterine leiomyosarcoma: a gynecologic oncology group study

Objective

To estimate activity and safety of trabectedin 1.5 mg/m2 IV over 24 hours every 3 weeks (1 cycle) in uterine leiomyosarcoma.

Methods

Patients with chemotherapy naive, advanced, persistent or recurrent uterine leiomyosarcoma, acceptable organ function and PS ≤ 2 were eligible. A two-stage design was utilized. Three responses were required in the first stage to initiate the second stage; the target sample size was 40 for the combined stages. If the true response rate was 10%, the study design provided a 95% chance of correctly classifying the treatment as “inactive.” Conversely, if the true response rate was 30%, then the average probability of correctly classifying the treatment as active would be 90%.

Results

Twenty patients were eligible and evaluable. The median number of cycles was 10 (123 total cycles, range 2-29). The number of patients with partial responses was 2 (10%; 95% confidence interval of 1.2%-31.7%). Response durations were 3.3 and 5.7 months. Ten patients had stable disease (50%). The median progression-free survival (PFS) and overall survival were 5.8 months and greater than 26.1 months (median not reached), respectively. Observed grade 3/4 toxicity included: neutropenia 16/20 (1 infection); thrombocytopenia 3/20; metabolic 3/20; anemia, gastrointestinal and vascular 1/20 each. There were no treatment related deaths nor cases of liver failure.

Conclusions

Although a second stage of accrual was not indicated based on the overall response rate, the drug was well tolerated.     

Fertility sparing surgery for treatment of early-stage cervical cancer: open vs. robotic radical trachelectomy

Objective

To compare the open versus robotic surgical approaches and provide surgical outcome data on patients who have undergone radical trachelectomy (RT).

Methods

We identified patients who underwent open (ORT) or robotic radical trachelectomy (RRT) between September 2005 and June 2011. Tumor characteristics, perioperative, operative and obstetrical outcomes were analyzed.

Results

Thirty-seven patients with early stage cervical cancer that desired future fertility underwent attempted radical trachelectomy, and 32 patients (20 with 1B1, 11 with 1A2, and 5 with 1A1 with LVSI/poorly differentiated histology) had successful completion of RT. Five (1 open/4 robotic) underwent conversion to radical hysterectomy secondary to close (< 5 mm) endocervical margin (p = 0.08). The median age at diagnosis was 28.9 years (range; 21.4-37.2), 70% were nulliparous, and 9 had a visible lesion. Twenty-five patients (68%) underwent ORT and 12 (32%) underwent RRT. RRT was associated with less blood loss (62.5 mL vs. 300 mL, p = 0.0001) and decreased length of postoperative stay (1 vs. 4 days, p < 0.001), with no difference in operative time or histopathologic outcomes. Twenty-three patients (62%) had no residual cervical disease on final pathology. Common long-term morbidities were irregular menstrual bleeding or amenorrhea (25%), cerclage erosion (13%), or cervical stenosis (9%). Although there was a higher rate of conversion to hysterectomy in the robotic surgery cohort, rates of serious morbidities among the cohorts were comparable (robotic: 33% vs. open: 24%, p = 0.70). Eleven (36%) patients are actively attempting pregnancy and three have achieved pregnancy. The median time of follow up is 17.0 months (range 0.30-64.9 months). There are no documented recurrences.

Conclusions

RRT results in less blood loss and decreased length of hospital stay with no compromise in histopathologic outcomes.     

Association of biochemical hyperandrogenism with type 2 diabetes and obesity in Chinese women with polycystic ovary syndrome

Objective

To evaluate the effect of hyperandrogenism on metabolic disorders among patients with polycystic ovary syndrome (PCOS) diagnosed using the Rotterdam criteria.

Methods

A retrospective analysis of the clinical records of 883 women with PCOS and 717 premenopausal controls identified from the general population.

Results

A total of 686 (77.7%) patients were classified with PCOS based on National Institutes of Health (NIH) criteria, and 164 out of 197 (83.2%) additional patients had no hyperandrogenism. Women with normal androgen levels exhibited lower frequencies of obesity, type 2 diabetes, acanthosis nigricans, genetic history of diabetes, and elevated Matsuda index compared with hyperandrogenic patients. Hyperandrogenemia, but not hirsutism, was independently associated with the risk for type 2 diabetes (odds ratio [OR] 5.7; P = 0.028) and obesity (OR 1.7; P = 0.005) among Chinese patients with PCOS.

Conclusions

Hyperandrogenemia is associated with type 2 diabetes and obesity in Chinese women with PCOS and should be considered at first-line management of hyperandrogenism and infertility due to PCOS.     

Air in the transfer catheter does not affect the success of embryo transfer

Objective

To investigate the effect on embryo transfer (ET) success of air loaded into the transfer catheter to bracket the embryo-containing medium.

Design

Prospective, randomized study.

Setting

University teaching hospital.

Patient(s)

One hundred two consecutive patients undergoing ET after IVF.

Intervention(s)

In group 1 (n = 52), embryos were loaded as follows: 200 μL of air in the syringe, 100-125 μL of air in the proximal part of the catheter, 20-25 μL of medium containing the embryos to be transferred, and 10 μL of air at the tip of the catheter. In group 2 (n = 50), the syringe and the entire catheter were filled with medium and the embryo-containing medium (20-25 μL) was aspirated without being bracketed by air spaces.

Main outcome measure(s)

Implantation and pregnancy rates.

Result(s)

No differences were found between groups 1 and 2 with respect to implantation and pregnancy rates.

Conclusion(s)

The air loaded into the transfer catheter to bracket the embryo-containing medium has no negative effect on ET success.     

Polycystic ovary syndrome and abnormalities in glucose tolerance

Objectives

To compare the prevalence of abnormal glucose tolerance (AGT) among women with polycystic ovary syndrome (PCOS) and controls, and assess risk factors associated with PCOS.

Method

A fasting oral glucose tolerance test after ingestion of 75 g of glucose was administered to 264 women with and 116 without PCOS. Moreover, fasting glucose, insulin, and testosterone levels were measured in the women with PCOS. Body mass index (BMI), waist-to-hip ratio (WHR), and homeostasis model assessment-insulin resistance (HOMA-IR) were calculated for each woman with PCOS.

Results

The AGT prevalence was 14.4% in the PCOS group and 11.2% in the control group (P = 0.17). The women with both PCOS and AGT had significantly higher BMIs, WHRs, testosterone levels, and HOMA-IR values than those with normal glucose tolerance.

Conclusion

While AGT was not associated with PCOS, the women with both PCOS and AGT were significantly more obese, hyperandrogenic, and insulin resistant than those with PCOS and normal glucose tolerance.     

Laparoscopic ovarian cystectomy of endometriomas: surgeons' experience may affect ovarian reserve and live-born rate in infertile patients with in vitro fertilization-intracytoplasmic sperm injection

Objective

To assess whether the laparoscopist's experience can affect ovarian reserve and pregnancy outcome in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) patients who previously underwent laparoscopic conservative treatment for ovarian endometriomas.

Study design

One hundred and forty-nine IVF-ICSI cycles with infertile patients who previously underwent laparoscopic conservative treatment for ovarian endometriomas were enrolled. There were 76 cycles with an inexperienced surgeon and 73 cycles with an experienced surgeon.

Results

The number of antral follicle count (7.5 ± 3.8 vs. 9.6 ± 6.6; p = 0.011), and live-born rate per cycle (9.3% vs. 32.9%; p < 0.001) were significantly lower in the inexperienced group comparing with the experienced group. However, the mean number of oocytes, fertilization rate, mean number of embryos transferred, rate of good-quality embryos transferred, implantation rate and clinical pregnancy were similar between both groups.

Conclusions

The experience of the laparoscopist may affect ovarian reserve and live-born rate after treating ovarian endometrioma in infertile women with IVF-ICSI.     

Maternal and perinatal outcomes of visceral leishmaniasis (kala-azar) treated with sodium stibogluconate in eastern Sudan

Objective

To investigate maternal and perinatal outcomes when pregnant women with visceral leishmaniasis (VL, also known as kala-azar) are treated with the antimonial sodium stibogluconate.

Method

Forty-two pregnant women with VL were treated with sodium stibogluconate at Gadarif Hospital, Gadarif, Sudan, and mother and child were followed up for 1 year.

Results

The treatment began at a mean ± SD of 24.4 ± 9.2 weeks of pregnancy. None of the patients had malaria or HIV. Two (4.7%) who received the treatment in the first trimester had miscarriages; 4 (4.9%) died from hepatic encephalopathy during the second week of treatment; and 2 (4.7%) had preterm deliveries. One of the newborns had a myelomeningocele and died at 2 hours, and the other died from VL at 2 months.

Conclusion

Preventive measures against VL should be employed in the region, and more research on VL and its treatment during pregnancy is needed.