Annals of Tropical Medicine and Public Health
Home About us Ahead Of Print Instructions Submission Subscribe Advertise Contact e-Alerts Editorial Board Login 
Users Online:7415
  Print this page  Email this page Small font sizeDefault font sizeIncrease font size
 


 
Table of Contents   
ORIGINAL ARTICLE  
Year : 2017  |  Volume : 10  |  Issue : 5  |  Page : 1292-1298
Clomiphene resistant polycystic ovarian syndrome: Analysis of outcomes following laparoscopic ovarian drilling in infertile women in Ilorin, North-central, Nigeria


1 Department of Obstetrics and Gynaecology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
2 Department of Obstetrics and Gynaecology, Usmanu Danfodiyo University Teaching Hospital, Sokoto, Nigeria
3 Department of Community Medicine, Federal Teaching Hospital, Ido-Ekiti, Ekiti State, Nigeria
4 Department of Anaesthesia, College of Health Sciences, University of Ilorin, Ilorin, Nigeria

Click here for correspondence address and email

Date of Web Publication6-Nov-2017
 

   Abstract 


Background: Laparoscopic ovarian drilling (LOD) is one-off treatment modality for clomiphene citrate (CC)-resistant polycystic ovarian syndrome (PCOS) avoiding the need of medical therapy and its attendant complications. Aims and Objectives: This study aimed at determining the efficacy of LOD in women with anovulatory infertility secondary to CC-resistant PCOS and factors influencing reproductive outcomes. Materials and Methods: A cross-sectional study of infertile women who underwent LOD on account of CC-resistant PCOS between January 2012 and December 2015 at a tertiary institution. Results: Patients aged 24–38 years (29.7 ± 3.6 years) and their body mass index (BMI) ranges from 20 to 35 (26.3 ± 4.3). The majority (90.5%) were nulliparous. Most (61.3%) had primary infertility. Their duration of infertility ranges from 1 to 13 years (4.3 ± 2.7) and ovarian volume ranges from 10 to 24 cm3 (mean, right ovary = 15.2 ± 3.2; left ovary = 16.3 ± 3.2). The number of drills per ovary ranged from 4 to 14 (mean, right ovary = 7.4 ± 2.1; left ovary = 7.3 ± 2.1) and the luteinizing hormone/follicle stimulating hormone (LH)/FSH ratio ranges from 2 to 6 (3.2 ± 1.4). All achieved spontaneous resumption of menses and ovulation with mean durations of 4.0 ± 1.8 days and 5.3 ± 3.2 weeks, respectively. Eighty-three (60.6%) clinical pregnancies were recorded, of which 68 (49.6%) resulted to live births (61 singletons and 7 twin births) and 14 (10.2%) early first trimester miscarriages. The mean time interval from LOD to pregnancy was 4.4 ± 1.1 months. There was a significant association between BMI, duration of infertility, FSH/LH ratio, and pregnancy outcomes (P < 0.05). Conclusion: LOD is the most preferred treatment modality for CC-resistant PCOS as it resulted in higher pregnancy rate.

Keywords: Clomiphene citrate-resistant, Ilorin, Nigeria, outcomes

How to cite this article:
Omokanye LO, Olatinwo AO, Panti A, Ibrahim S, Durowade KA, Oyedepo OO, Ige O, Adegboye MB. Clomiphene resistant polycystic ovarian syndrome: Analysis of outcomes following laparoscopic ovarian drilling in infertile women in Ilorin, North-central, Nigeria. Ann Trop Med Public Health 2017;10:1292-8

How to cite this URL:
Omokanye LO, Olatinwo AO, Panti A, Ibrahim S, Durowade KA, Oyedepo OO, Ige O, Adegboye MB. Clomiphene resistant polycystic ovarian syndrome: Analysis of outcomes following laparoscopic ovarian drilling in infertile women in Ilorin, North-central, Nigeria. Ann Trop Med Public Health [serial online] 2017 [cited 2019 Dec 11];10:1292-8. Available from: http://www.atmph.org/text.asp?2017/10/5/1292/217544



   Introduction Top


Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women of reproductive age.[1] It is associated with chronic anovulation and infertility. The diagnosis is made by clinical and ancillary investigations revealing the presence of irregular menstrual cycles, an ovulation, elevated total, and free testosterone levels (hyperandrgenemia), and the presence of polycystic ovaries (ovarian morphology as the presence of 12 or more follicles measuring 2–9 mm in diameter and an increased ovarian volume >10 cm 3).[2]

In most cases, ovulation can be induced with clomiphene citrate (CC), a selective estrogen receptor modulator; however, 25% of patients fail to ovulate/conceive after 3–6 cycles of treatment with CC (CC-resistant/failure) and require alternative treatments.[3] The reason may be a high intraovarian androgen environment affecting the oocyte quality as well as ovulation, tenacious cervical mucus and unfavorable endometrium.[4] Other treatment modalities for clomiphene resistant PCOS included gonadotrophins and/or metformin as well as surgical interventions.[2]

Surgical wedge resection was the first established treatment offered to infertile women with anovulatory PCOS but was largely abandoned due to a significant risk of postoperative pelvic adhesions which could account for low pregnancy rate.[2] Laparoscopic ovarian drilling (LOD) was introduced by Gjonnaess in 1984 as an alternative surgical method with the aim of minimizing postsurgical adhesions and improved pregnancy rate.[5] Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception or that subsequent medical ovulation induction becomes easier.[2] The most plausible mechanisms of action are the destruction of ovarian follicles and a part of the ovarian stroma, inducing a reduction of serum androgens and inhibin levels, which results in an increase of follicle stimulating hormone (FSH) and restore the ovulation function.[5] Laparoscopic ovarian drilling may also increase ovarian blood flow, allowing a high delivery of gonadotrophins and postsurgical local growth factors.[5]

Currently, LOD is a second-line treatment in PCOS patients, especially those with CC resistance.[1],[5] The potential benefits of LOD include spontaneous mono-follicular ovulation thereby minimizing the need for intensive monitoring and eliminating the risk of ovarian hyper stimulation and lower cost.[2],[5] These have made LOD an attractive option of ovulation induction for CC-resistant in resource-limited countries as the cost of gonadotrophins is beyond the reach of majority of infertile couples. Hence, the study aimed at a determining the efficacy of laparoscopic ovarian drilling (LOD) in women with anovulatory infertility secondary to CC-resistant PCOS and factors influencing reproductive outcomes.


   Materials and Methods Top


This is a cross-sectional prospective study of infertile women with CC-resistant PCOS (diagnosed using Rotterdam criteria) who underwent LOD at the Assisted Reproductive Technology Unit of University of Ilorin Teaching Hospital, Ilorin between January 1, 2012 and December 31, 2015. Infertile women who were found to have inadequate coital exposure in the past 1 year, with the bilateral tubal blockade, grade III-IV endometriosis and whose spouse has male factor infertility were excluded from the study. All patients with abnormal hormone profiles, prolactin, hypo- and hyper-thyroidism were treated before enrolled into the study. Patients' information obtained included sociodemographic variables, intra-operative findings, and reproductive outcomes.

Informed consent was obtained from 137 eligible patients for the study. All patients were evaluated and confirmed fit for surgery. A complete blood counts, urinalysis, electrolyte, urea, and creatinine estimation were requested preoperatively. Patients also had bowel preparation with Dulcolax and enema saponis. All procedures were performed under general anesthesia. Pneumoperitoneum was created with Veress needles using the inferior crease of the umbilicus in the midline. The 10 mm infra- umbilical port was placed on the infra umbilical crease through a transverse incision and two 5 mm lateral ports were placed in the lower abdomen just above the anterior superior illac spine lateral to inferior epigastric vessels using baseball diamond concept.

The laparoscope was then introduced through the infra-umbilical port. A general inspection of the pelvis was performed looking for other infertility factors. The tubes are examined, and chromotubation for tubal patency was carried out.

A monopolar hook was introduced at right angle to the ovary avoiding injury to the hilum. Forty (40) watts of cutting current was used making 4 to 15 holes each lasting 4 s at a depth of 3–4 mm to the ovaries. A thorough suction irrigation of the ovaries and peritoneal lavage with normal saline was done after the drill to cool the ovaries and clear the pelvis of any blood clots and debris. The port wound was closed by subcuticular suturing using Vicryl 2/0.

Patients were followed up during subsequent visits and also with the aid of mobile telephone to obtain information as regards resumption of menstruation and ovulation. Ovulation was confirmed using ovulation test kit (predict ®), day 12-14 follicular transvaginal ultrasound study and any pregnancy after the procedure. However, if natural conception fails after 3 months of the procedure, they were subjected to ovulation induction with an incremental dose of 50 mg of CC on days 2–6 to a maximum of 150 mg daily per cycle and timed intercourse for three consecutive cycles.

Statistical analysis

Data were collected using a pro forma designed for that purpose, and descriptive statistical analysis was performed using a commercial statistical package (SPSS/PC version 16.0, SPSS Inc., Chicago, III, USA). The value of P < 0.05 was considered to be statistically significant.


   Results Top


One hundred and thirty-seven infertile women underwent successful LOD during the study period with a mean duration of follow-up time of 9.3 ± 6.5 months (range: 3–24 months). The patients aged 24–38 years with a mean age of 29.7 ± 3.6 years and their body mass index (BMI) ranges from 20 to 35 (26.3 ± 4.3). Majority (90.5%) were nulliparous. One hundred and ten (80.3%) belong to the middle social class. Most (61.3%) had primary infertility. The mean age of their husband was 35.7 ± 5.3 years (range 26–50 years). Their duration of infertility ranges from 1 to 13 years (4.3 ± 2.7) and the ovarian volume ranges from 10 to 24 cm 3 (mean, right ovary = 15.2 ± 3.2; left ovary = 16.3 ± 3.2). The number of drills per ovary ranged from 4 to 14 (mean, right ovary = 7.4 ± 2.1; left ovary = 7.3 ± 2.1) and the luteinizing hormone (LH)/FSH ratio ranges from 2 to 6 (3.2 ± 1.4). Most 65 (47.4%) CC following failure of achieving natural conception after 3 months of LOD [Table 1].
Table 1: Sociodemographic characteristics of patients (n=137)

Click here to view


All achieved spontaneous resumption of menses and ovulation following ovarian drilling with mean durations of 4.0 ± 1.8 days and 5.3 ± 3.2 weeks, respectively. Eighty-three (60.6%) clinical pregnancies were recorded, of which 68 (49.6%) resulted to live birth (61 singletons and 7 twin births) and 14 (10.2%) early first trimester miscarriages. The mean time interval from LOD to pregnancy was 4.4 ± 1.1 months [Table 2].
Table 2: Outcomes following laparoscopic ovarian drilling (n=137)

Click here to view


There was a significant association between BMI, duration of infertility, FSH/LH ratio and pregnancy outcomes (P < 0.05). However, patients' age, parity, husband's age, social class, types of infertility, ovarian volume, the number of drills per ovary did not significantly affect the outcome [Table 3].
Table 3: Relationships between the sociodemographic characteristics of patients and their pregnancy outcomes

Click here to view



   Discussion Top


The LOD procedure has been widely used to induce ovulation in PCOS women after failure of CC treatment and the spontaneous ovulation and pregnancy rates achieved in the current study was comparable to those reported in the literature.[4],[5],[6],[7],[8],[9],[10] The study analyzed the efficacy of LOD in women with anovulatory Infertility due to CC-resistant PCOS as well as factors influencing the reproductive outcome.

All the patients that had LOD in the study resumed normal menses and ovulation with the mean duration of 4.0 ± 1.8 days and 5.3 ± 3.2 weeks, respectively. This is higher than previous studies that recorded 67.3% and 58.8%, respectively [6] and also 73.3% and 82%[7] perhaps the difference may be attributed to the fact that in the current study the number of drills, i.e., thermal energy on the ovaries was adjusted based on the size of the ovary. Adjusting the dose of thermal energy depending on the ovarian volume was found to give better outcomes.[4] However there was no significant difference between ovarian volume, the number of drills per ovary and reproductive outcome.

The cumulative conception rate of the study was 60% with a live birth rate of 49.6%. A similar study recorded a pregnancy rate of 61%.[8] This is higher than 46.9% conception rate recorded in another study [6] but lower than 84.5% pregnancy rate recorded in a similar study.[9] It was reported that the beneficial effect of LOD is of limited duration. In most studies, the effect last up to 1 year,[8] but pregnancies have been known to occur after 12 months in some studies.[8] However in the current study, most of the patients conceived in the first 4–6 month after LOD. The mean interval of conception and LOD was 4.4 ± 1.1 month. This result is comparable to 3.95 ± 4.1 recorded in another study.[8]

In this study, 10.2% of pregnancies recorded ended as spontaneous abortions within the first trimester and 7 twin pregnancies were recorded. In a previous study in India, 6% of pregnancies ended in spontaneous abortions.[10] However, in most previous studies multiple pregnancy was not recorded following LOD [6],[7],[10] probably it was recorded in this study because the study was conducted in an area where there is high rate of twining [11],[12] and could have been as a result of CC [13] that was administered to some patients 3 months after LOD because multiple pregnancy rarely occurred in infertile women who conceive following LOD.[7]

All our patients had anovulatory infertility ranging from 1 to more than 10 years duration and had been unsuccessfully treated with CC to a maximum of 150 mg/day before LOD. Patients with CC-resistant PCOS have the choice of gonadotropins therapy or LOD. However, LOD is more cost effective than gonadotropins as single treatment result in several mono ovulatory cycle thus allowing multiple attempts at conception, whereas one course of gonadotropin therapy yields a single ovulatory cycle with the inherent need for intensive monitoring.[1] The gonadotropins are also very costly and may not be readily affordable by most patients', they are also temperature regulated and issues of potency is at risk because some pharmaceutical stores in our environment cannot stock it properly because of infrequent electricity supply.

In this study, the evaluation of influence on reproductive outcome of LOD was also done. Three main factors were shown to have significant impact on efficacy of LOD, i.e., the duration of infertility, BMI and LH/FSH ratio. LOD had a successful pregnancy outcome in patients with normal BMI (84.4%) and in those whose BMI is <30 kg/m 2 ( 72.6%) but not successful in those with BMI of >30 kg/m 2, this finding is similar to that observed in previous studies;[7],[8],[9],[10] hence, alternative methods of treatment may need to be employed for this group of patients such as weight reduction, metformin treatment, gonadotropin therapy or IVF to achieve conception.[10]

The duration of infertility of 5 years and below had the strongest impact as a predictor of success. This result is in agreement with previous study.[6] A possible explanation for the role of the duration of infertility may be the emergence of other subfertility factors as duration of infertility increases.[6]

In this study, all patients who had LH/FSH ratio of 2 got pregnant following LOD. In few studies it was observed that LOD responders who had lower pretreatment LH level or a lower LH/FSH ratio were more likely to continue to benefit from treatment for a longer period compared with those who had higher pretreatment LH or LH/FSH ratio are more likely to experience a recurrence of their anovulatory status after several month of treatment.[10] In a similar study LOD responder with pretreatment serum LH concentration of 12 IU/L achieved higher pregnancy rate.[6] LOD reduces serum concentration of LH or LH/FSH ratio to follow up period, as LH levels fall spontaneous ovulation and conception rate increases.[7]


   Conclusion Top


LOD is an effective treatment modality in CC-resistant PCOS. It results in high rate of regularization of menses, ovulation, and conception rate without major complications. It is more effective in infertility duration of 5 years and below, pretreatment LH/FHS ratio of 2 and in those patients with normal BMI and BMI <30 kg/m 2. LOD is therefore recommended in our environment for the treatment of CC-resistant PCOS.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Mitra S, Nayak PK, Agrawal S. Laparoscopic ovarian drilling: An alternative but not the ultimate in the management of polycystic ovary syndrome. J Nat Sci Biol Med 2015;6:40-8.  Back to cited text no. 1
[PUBMED]    
2.
Omokanye LO, Olatinwo AW, Durowade KA, Panti AA, Salaudeen AG, Adewara EO. A review of pregnancy outcomes following laparoscopic ovarian drilling for infertile women with clomiphene resistant polycystic ovarian syndrome (PCOS) at a public health institution in Ilorin, Nigeria. Trop J Obstet Gynaecol 2014;31:74-81.  Back to cited text no. 2
    
3.
Seyedoshohadaei F, Zandvakily F, Shahgeibi S. Comparison of the effectiveness of clomiphene citrare, tamoxifen and letrozole in ovulation induction in infertility due to isolated unovulation. Iran J Reprod Med 2012;10:531-6.  Back to cited text no. 3
[PUBMED]    
4.
Dasari P. Laparoscopic ovarian drilling for infertile PCOS women who are resistant to oral ovulation-inducing drugs. Fertil Sci Res 2015;2:15-8.  Back to cited text no. 4
  [Full text]  
5.
Lebbi I, Ben Temime R, Fadhlaoui A, Feki A. Ovarian drilling in PCOS: Is it really useful? Front Surg 2015;2:30.  Back to cited text no. 5
[PUBMED]    
6.
Safia SM, Dawoud A, Misbah S, Tania S. Ovulation induction using ovarian drilling in women with polycystic ovarian syndrome: Predictors of success. Biomedica 2010;26:130-4.  Back to cited text no. 6
    
7.
Butt F. Laparoscopic ovarian drilling by diathermy for ovulation in infertile women with polycystic ovarian syndrome. Annals 2011;7:150-6.  Back to cited text no. 7
    
8.
Cleemann L, Lauszusand BP, Trolle B. Laparoscopic ovarian drilling as first line of treatment in infertile women with polycystic ovary syndrome. Gynaecol Endocrinol 2004;18:138-43.  Back to cited text no. 8
    
9.
Rao SI, Kokeb H, Sadiq R. Polycystic ovarian disease: The diagnosis and management. Prof Med J 2006;13:186-91.  Back to cited text no. 9
    
10.
Deepti S, Bhule S, Satorupa M. Role of laparoscopic ovarian drilling as a first line management in Infertility with polycystic ovarian disease. JSAFOG 2010;2:123-6.  Back to cited text no. 10
    
11.
Iyiola OA, Oyeyemi FB, Raheem UA, Mark FO. Frequency of twinning in Kwara State, North central, Nigeria. EJMHG 2013;14:29-35.  Back to cited text no. 11
    
12.
Isiaka-Lawal S, Adeshina KT, Saidu R, Ijaiya MA, Jimoh AA, Aderibigbe SA. A review of twin gestation in a tertiary health institution in North central, Nigeria. Res J Med Sci 2009;3:198-201.  Back to cited text no. 12
    
13.
Waheed SS, Siddique T, Farzand S. Evaluation of complications associated with twin pregnancy. PJMHS 2013;7:414-6.  Back to cited text no. 13
    

Top
Correspondence Address:
Lukman Omotayo Omokanye
Department of Obstetrics and Gynaecology, College of Health Sciences, University of Ilorin, Ilorin, Nigeria
Nigeria
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ATMPH.ATMPH_774_16

Rights and Permissions



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *


    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusion
    References
    Article Tables

 Article Access Statistics
    Viewed1802    
    Printed25    
    Emailed0    
    PDF Downloaded19    
    Comments [Add]    

Recommend this journal