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 Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 1  |  Issue : 1  |  Page : 2-5

Outcome of in vitro fertilization procedure at a private fertility center in Nnewi, South-East Nigeria


1 Assisted Reproductive Unit, Life Specialist Hospital Ltd.; Department of Obstetrics and Gynaecology, Nnamdi Azikiwe University, Nnewi Campus, PMB 5025, Nnewi, Anambra State, Nigeria
2 Department of Obstetrics and Gynaecology, Nnamdi Azikiwe University, Nnewi Campus, PMB 5025, Nnewi, Anambra State, Nigeria
3 Assisted Reproductive Unit, University of Benin Teaching Hospital, Benin City, Nigeria
4 Department of Community Medicine, Chukwuemeka Odumegwu Ojukwu University, Awka, Nigeria
5 Assisted Reproductive Unit, Life Specialist Hospital Ltd., Nnewi, Anambra State, Nigeria

Date of Web Publication7-Sep-2016

Correspondence Address:
Joseph Ifeanyichukwu Ikechebelu
Department of Obstetrics and Gynaecology, Nnamdi Azikiwe University, Nnewi Campus, Anambra State
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2468-8452.189960

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  Abstract 

Background: Infertility has grown to be a major health and social challenge in our environment that a childless marriage is regarded as a failed marriage. Couples are therefore ready to do all within their power to achieve pregnancy and have a baby of their own. This is the yawning gap assisted reproductive technology is fulfilling. Objective: To determine the outcome of in vitro fertilization (IVF) procedures 2 years after the commencement of the IVF program in a private hospital setting in Nnewi, Nigeria. Methods: From October 1, 2010 to September 30, 2012, 115 couples had conventional IVF procedures in batches of 10-15 couples. The outcome measures were clinical pregnancy rate, miscarriage rate, live birth rate, and sex ratio following one or two cycles of treatment. The results were analyzed using Epi info software 2013 version 7.0. Results: The mean age of the participants was 43.7 ± 3.5 years. The maximum number of embryos transferred per woman was four and minimum was one. The rates of clinical pregnancy, live births and multiple pregnancies were 30%, 18.3%, and 6.0%, respectively. Of the 31 women who conceived, 21 (67.7%) delivered live infants and 10 (32.3%) aborted in the first trimester. There was no case of ectopic pregnancy. The male:female sex ratio was 2:1. The mean endometrial thickness at embryo transfer (ET) was 8.9 ± 2.3 mm. Conclusion: The success rate of IVF-ET was good even in low resource settings and optimal endometrial thickness prior to ET may be one of the key success factors. The preponderance of male sex infants in our IVF births is acceptable to the couples who ordinarily have a preference for male infant.

Keywords: Assisted conception, infertility, in vitro fertilization, Nnewi, ovarian stimulation


How to cite this article:
Ikechebelu JI, Eleje GU, Ibadin K, Joe-Ikechebelu NN, Nwaefulu K, Okwelogu SI. Outcome of in vitro fertilization procedure at a private fertility center in Nnewi, South-East Nigeria. Afr J Infertil Assist Concept 2016;1:2-5

How to cite this URL:
Ikechebelu JI, Eleje GU, Ibadin K, Joe-Ikechebelu NN, Nwaefulu K, Okwelogu SI. Outcome of in vitro fertilization procedure at a private fertility center in Nnewi, South-East Nigeria. Afr J Infertil Assist Concept [serial online] 2016 [cited 2017 Aug 19];1:2-5. Available from: http://www.afrijiac.org/text.asp?2016/1/1/2/189960


  Introduction Top


Since its introduction in 1978, in vitro fertilization and embryo transfer (IVF-ET) has grown to be the most advanced method of infertility treatment even in developing countries like Nigeria. [1],[2],[3] However, the current practice is largely different from that which was used during the early days of its beginning. Currently, IVF-ET is performed not only for tubal infertility, but also for unexplained and male factor infertility, endometriosis, and ovulatory disorders. [4],[5] In Canada, almost half of all IVF cycles performed in 2001 were for nontubal indications. [5]

Although advances in laboratory technology and clinical practice have permitted IVF to progress, it still remains expensive and is associated with potential risks to the mother and fetus. [1] Because multiple embryos are transferred in the majority of assisted reproductive technology (ART) procedures, ART has been associated with a substantial risk for multiple gestation and multiple births. [1] Multiple births are associated with greater health problems for mothers and infants, including higher rates of caesarean deliveries, prematurity, low birth weight, infant death, elevated risk for birth defects, and disability. [1] Further, even singleton infants conceived with ART have a higher risk of low birth weight. [1],[2]

Management of IVF-ET pregnancies is often intricate as the couples and consulting obstetricians have extreme apprehension and nervousness about the outcome of such procedures and their resulting pregnancies. The outcomes of IVF procedures in Nigerian private sector have been under investigated. This study was therefore undertaken to determine the outcomes of such IVF procedures in a private fertility center in a low resource setting.


  Methods Top


Population

Couples who had IVF and ET treatment following established diagnosis of infertility at the Life Fertility Centre of Life Specialist Hospital Nnewi, Nigeria, over a 2 year period (October 2010 to September 2012).

Study design

A retrospective review of the case files and treatment protocol of couples that had conventional IVF procedure during the study period.

Patient recruitment

The IVF treatment cycles were performed in batches of 10-15 couples to optimize available resources and manpower. The patients were adequately counselled, written consent obtainedz and then recruited for the procedure before down regulation was commenced.

Down regulation

A baseline serum concentration of luteinizing hormone, follicle-stimulating hormone (FSH), and estradiol on day 2 or 3 of the menstrual cycle preceding the treatment cycle was done to assess the ovarian reserve. A transvaginal scan was also performed before the commencement of GnRH agonist administration on day 21 of the menstrual cycle. The long protocol was used for down regulation with daily injections of 0.5 mg buserelin acetate (Suprefact ® , Hoechst AG, Frankfurt, Germany), self-administered subcutaneously until ovarian suppression is achieved. This was confirmed by obtaining an endometrial thickness <3 mm on pre-FSH transvaginal ultrasound or estradiol level below 50 pg/ml. Ovarian stimulation was commenced when all the women in the batch had down regulated usually by day 14-28 of treatment.

Ovarian stimulation

Stimulation of multiple follicular growth was achieved with human menopausal gonadotrophin (Diclair-HP HMG, or Menogon, Germany R). Women <34 years of age were started on four ampoules (300 IU) daily and those 35 years and above were on 5-6 ampoules (375-450 IU) daily. The ovarian response to stimulation was monitored by transvaginal ultrasound assessment of follicular and endometrial growth on days 6 and 9 of stimulation. A prehuman chorionic gonadotropin (pre-hCG) scan was done on day 11 or 12 and ovulation triggered by a single injection of 10,000 IU of human chorionic gonadotrophin (Diclair-HP HCG, R Germany), when at least 2 or more follicles had reached the diameter of 17 mm or more. Oocyte retrieval was scheduled 36 h after hCG injection.

Oocyte retrieval

This was performed by transvaginal ultrasound-guided aspiration 36 h after hCG administration using a 17-gauge aspiration needle. Follicular fluid was aspirated into sterile falcon round bottom tubes (falcon, 14 ml) placed in digiblock to maintain temperature at 37°C. These were transferred to the embryology unit and poured into the falcon tissue culture dish. Oocytes were isolated under a stereomicroscope, washed, and transferred into already equilibrated culture media and incubated at 37°C, under 5% CO 2 with saturated humidity for 2-4 h before insemination with prepared semen.

Sperm collection and preparation

The semen was collected preferable by masturbation (or coitus interruptus with spermicide-free condoms where masturbation is not possible) on the day of oocyte retrieval and processed. Sperm wash technique with origin sperm preparation medium is used and the final sample is incubated at 37°C. [6]

In vitro fertilization

Oocytes were inseminated with prepared sperm specimen (about 200,000 spermatozoa per well) and returned to the incubator. They were considered as normally fertilized if two pronuclei and two polar bodies were observed 18-20 h after insemination. [7] Early cleavage was checked at 24 h after fertilization. On day 2, normal embryos were observed to have 2-4 blastomeres and embryo morphology was evaluated by microscopic observation of morphological criteria, such as size, number and regularity of blastomeres, fragmentation percentages, and zona pelluicida thickness.

Embryo transfer

On Day 2, ET was performed with the embryos at 2-4 cell stage. One to four embryos were transferred (depending on the age of the patient and available embryos), into the endometrial cavity (>1 cm away from the fundus) under ultrasound guidance. The 23 cm soft embryo replacement catheter with or without stylet (Wallace Smith Medical international Ltd., Mexico, USA) was used.

Luteal support

The luteal phase support was commenced on the day of oocyte retrieval and continued up to 14 weeks of gestation in successful cycles. Daily progesterone pessary (cyclogest ® 400 mg, Actavis, Barnstaple, EX32 8NS, UK) inserted rectally before ET and vaginally after ET at doses of 400 mg in self cycles and 800 mg in recipient cycles was used. Biochemical pregnancy was determined by maternal serum HCG level on day 14 post-ET, while clinical pregnancy was confirmed by ultrasound detection of a gestation sac at 4 weeks post-ET.

Outcome measures

Our primary end-point was the live birth rate (per cycle and per transfer), and the secondary end-points were chemical and clinical pregnancy rates, spontaneous abortion rate, multiple pregnancy rate, and sex distribution rate. The data regarding pregnancy follow-up and delivery were also extracted.

Statistical analysis

The results were analyzed by Epi info software 2013 version 7.0 (Centers for Disease Control and Prevention-CDC, Atlanta, USA), and presented as mean ± standard deviation. The statistical significance of differences between groups for continuous variables was assessed and differences in proportions were assessed using Mantel-Henszel's test or Fisher exact test, where appropriate. P < 0.05 was considered statistically significant.


  Results Top


Between October 2010 and September 2012, 115 procedures were done in the IVF section. The mean age of the participants was 43.7 ± 3.5 years. As a result, 31/115 (27.0%) pregnancies were recorded of which 10/31 (32.3%) clients lost their pregnancy between 5 th and 13 th week, whereas 21/31 (67.7%) were carried to age of viability and delivered. Eighty-four of the 115 (73.0%) clients did not achieve pregnancy. This is shown in [Table 1]. The mean endometrial thickness at ET was 8.1 ± 2.3 mm.
Table 1: Pregnancy rate following one treatment cycle of in vitro fertilization and embryo transfer

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[Table 2] shows the type of live births following one or two treatment cycles of IVF. Twin pregnancies accounted for 8/21 (38.1%) deliveries, whereas higher order multiple pregnancies accounted for 3/21 (14.3%) deliveries. Thus, of the 33 infants delivered, multiple pregnancies gave rise to 20 (60.6%) infants.
Table 2: Type of live births following one or two treatment cycles of in vitro fertilization

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The sex distribution of the infants was 21/33 (63.6%) boys and 13/33 (36.4%) girls, giving a male:female ratio of 2:1. The relationship between the maternal age and pregnancy rates is shown in [Table 3]. Older people give in to IVF more than women of younger age. Optimal pregnancy rate was significantly higher in the age group 35-39 years (P < 0.05).
Table 3: The relationship between the maternal age and pregnancy rates

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  Discussion Top


Indeed, the use of IVF has increased substantially in Nigeria since the beginning of its practice in Nigeria. The impact of IVF on rates of multiple-birth is also substantial because more than half of IVF infants (60.6%) in our series were born in multiple births. On average, three embryos were transferred among women recruited. In a previous study on the outcomes of IVF in Nigeria by Orhue et al., [4] the rate of clinical pregnancy was 30%. This was similar to our findings of 27.0%.

A number of factors may be responsible for the success recorded in our study. It could be the level of endometrial thickness at the time of ET, which was 8.9 ± 2.3 mm. In a previous work by Okohue et al. [8] in Nigeria and Zhao et al. [9] in China, a triple-line pattern combined with an optimal endometrial thickness (7-14 mm) was associated with a positive pregnancy outcome compared with those with a thickness of <7 mm or >14 mm.

In the present study, the multiple pregnancy rate was 40%, which was higher than the multiple pregnancy rate of 6.0% documented by Orhue et al. [4] in a public hospital in Benin city, Nigeria. Improvements in implantation rates removed the pressure to transfer multiple embryos. In a study in Sweden by Finnström et al., [10] the rate of multiple births and preterm births decreased dramatically, with a better neonatal outcome, including reduced neonatal mortality. In another published Swedish study till 1992, the twinning rate increased to a maximum of about 30% and then declined to 5% toward the end of the period, whereas higher order multiples nearly disappeared. [11] Similarly, a Finnish study by Källén et al. compared outcomes of IVF-ET for the 1991-1993 and 1998-1999 periods and found a decline in the multiple birth rates. [11] In our case, three women had high order multiple pregnancies. This possibility, as well as recognition of complications associated with multiple pregnancies, has led to the promotion of an elective single ET policy [12] that became widely adopted in many European countries. [13]

In Orhue et al. study, the rates of abortion were 6.6% which was lower than our findings of 8.7%. This finding was lower than 21.9% reported by Ben-Rafael et al. in Philadelphia, USA. [14] In our findings, all the abortions occurred in the first trimester. The explanation for the high rate and timing of miscarriage in the first trimester remain unclear. However, previous study by Shoham et al. in Israel concluded that the abortion rate in pregnancies achieved after IVF-ET procedures does not appear to be higher than that of the general population, particularly when early pregnancy loss, advanced maternal age, the infertility status, and the increased incidence of multiple pregnancies occurring in these patients are taken into consideration. [15]

Although only conventional IVF was the procedure used in the study, no difference in outcome existed between IVF and intracytoplasmic sperm injection or between the use of fresh and cryopreserved embryos in a study in Sweden by Finnström et al. [10] However, Finnström et al. [10] study documented that children born after blastocyst transfer had a slightly higher risk for preterm birth and congenital malformations than children born after cleavage stage transfer.

It was not clear why optimal pregnancy rate was significantly higher in the age group 35-39 years. Optimal pregnancy rate is expected to be higher in lower age groups when the women are <35 years. Could it be due to higher dose of human menopausal gonadotrophin used for ovarian stimulation or higher number of embryos transferred in this age group relative in women <35 years? This then calls for further studies to explore this peculiar finding.

This study has a number of clinical implications. Conventional IVF was much less effective when semen parameters were below the reference values for concentration (oligozoospermia), motility (asthenozoospermia), and morphology (teratozoopermia), resulting in significantly lower fertilization rates and fewer embryos available for transfer. [16] This is important because, only conventional IVF (not intra cytoplasmic sperm injection) was the practice in the hospital as at the time of study.


  Conclusion Top


The present study showed that IVF-ET had a good success rate even in low resource settings of Nnewi, Nigeria, and optimal endometrial thickness prior to ET may be one of the key success factors. The preponderance of male sex in our IVF cycle and life birth rate is encouraging as many couples ordinarily prefer this trend.

Study limitations

A limitation of our study is the retrospective design. Although our sample size is relatively small, our study provides an important findings/evidence that there is good success rate of IVF-ET procedures in Nigeria. We did not assess cycle cancelation rate or ovarian hyper stimulation syndrome rate. Further studies with larger series of women are needed to confirm these useful and successful findings in our low resource settings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Ramalingam M, Durgadevi P, Mahmood T. In vitro fertilization. Obstet Gynaecol Reprod Med 2016;26:200-9.  Back to cited text no. 1
    
2.
Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet 1978;2:366.  Back to cited text no. 2
    
3.
Obioha JA, Ikechebelu JI, Eleje GU, Joe-Ikechebelu NN. Knowledge and attitude of nurses towards in-vitro fertilization: A prospective cohort study. Obstet Gynecol Cases Rev 2014;1:006.  Back to cited text no. 3
    
4.
Orhue AA, Aziken ME, Osemwenkha AP, Ibadin KO, Odoma G. In vitro fertilization at a public hospital in Nigeria. Int J Gynaecol Obstet 2012;118:56-60.  Back to cited text no. 4
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Gunby J, Daya S. Assisted reproductive technologies (ART) in Canada: 2001 results from the Canadian ART Register. Fertil Steril 2005;84:590-9.  Back to cited text no. 5
    
6.
WHO. WHO Laboratory Manual for the Examination and Processing of Human Semen. 5 th ed. Geneva: World Health Organization; 2010. p. 224.  Back to cited text no. 6
    
7.
Lim JH, Yang SH, Xu Y, Yoon SH, Chian RC. Selection of patients for natural cycle in vitro fertilization combined with in vitro maturation of immature oocytes. Fertil Steril 2009;91:1050-5.  Back to cited text no. 7
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8.
Okohue JE, Onuh SO, Ebeigbe P, Shaibu I, Wada I, Ikimalo JI, et al. The effect of endometrial thickness on in vitro fertilization (IVF)-embryo transfer/intracytoplasmic sperm injection (ICSI) outcome. Afr J Reprod Health 2009;13:113-21.  Back to cited text no. 8
    
9.
Zhao J, Zhang Q, Li Y. The effect of endometrial thickness and pattern measured by ultrasonography on pregnancy outcomes during IVF-ET cycles. Reprod Biol Endocrinol 2012;10:100.  Back to cited text no. 9
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10.
Finnström O, Källén B, Lindam A, Nilsson E, Nygren KG, Olausson PO. Maternal and child outcome after in vitro fertilization--a review of 25 years of population-based data from Sweden. Acta Obstet Gynecol Scand 2011;90:494-500.  Back to cited text no. 10
    
11.
Källén B, Finnström O, Lindam A, Nilsson E, Nygren KG, Otterblad Olausson P. Trends in delivery and neonatal outcome after in vitro fertilization in Sweden: Data for 25 years. Hum Reprod 2010;25:1026-34.  Back to cited text no. 11
    
12.
Klemetti R, Gissler M, Hemminki E. Comparison of perinatal health of children born from IVF in Finland in the early and late 1990s. Hum Reprod 2002;17:2192-8.  Back to cited text no. 12
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Ombelet W, De Sutter P, Van der Elst J, Martens G. Multiple gestation and infertility treatment: Registration, reflection and reaction-the Belgian project. Hum Reprod Update 2005;11:3-14.  Back to cited text no. 13
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14.
Ben-Rafael Z, Fateh M, Flickinger GL, Tureck R, Blasco L, Mastroianni L Jr. Incidence of abortion in pregnancies after in vitro fertilization and embryo transfer. Obstet Gynecol 1988;71:297-300.  Back to cited text no. 14
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15.
Shoham Z, Zosmer A, Insler V. Early miscarriage and fetal malformations after induction of ovulation (by clomiphene citrate and/or human menotropins), in vitro fertilization, and gamete intrafallopian transfer. Fertil Steril 1991;55:1-11.  Back to cited text no. 15
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16.
Källén B, Finnström O, Nygren KG, Olausson PO. In vitro fertilization (IVF) in Sweden: Infant outcome after different IVF fertilization methods. Fertil Steril 2005;84:611-7.  Back to cited text no. 16
    



 
 
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  [Table 1], [Table 2], [Table 3]



 

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