Fertility and pregnancy outcome among women undergoing assisted reproductive technology treatment in Windhoek, Namibia

Abstract

Purpose

Infertility has been defined as a couple’s failure to conceive after regular and unprotected coitus for 1 year or six months, depending on the age of the female counterpart. Although infertility can result from both the male and/or the female, often the female partner faces pressure since it is believed in some African cultures that a woman without children is like a tree without leaves. The aim of this study was to determine the prevalence of successful pregnancy outcomes among infertile women undergoing assisted reproductive technology (ART) treatment at the Cape Windhoek Fertility Clinic.

Methods

This was a prospective and descriptive cross-sectional case reference study encompassing 178 infertile women visiting the Cape Windhoek Fertility Clinic for ART treatment.

Results

The vast majority of the participants (81.5%) were married women. From the 178 infertile women, 96 (53.9%) suffered from primary and 82 (46.1%) from secondary infertility. The predominant cause of complications for infertility among the women studied was defective ovulation (28.7%) and the most common ART treatment administered was IVF/ICSI (52.2%). Only a third (33.1%) of the women who received ART treatment eventually fell pregnant.

Conclusion

The outcome of this study may not give a clear indication of the prevalence of infertility among women in the entire Namibian nation due to the costs involved with ART treatment offered mainly at privately owned hospitals and/or clinics, thereby resulting in those who cannot afford treatment to be left out despite being infertile.

Introduction

Infertility is a global burden and requires attention. According to the World Health Organization (WHO), 25% of the couples in developing countries are affected by infertility [1]. A study seeking to establish global trends of infertility conducted by Mascarenhas et al. [2] listed Sub-Saharan Africa and South Asia among the regions with the highest prevalence rates of infertility. Moreover, the study also noted that the prevalence of primary infertility was higher in Central Sub-Saharan Africa compared to Eastern and Southern Africa. Similar studies have further shown that the worldwide prevalence of couples affected by infertility was between 10 and 15%, while 20–60% of couples are affected in Africa alone [3, 4].

In most of the developing world, particularly Africa, having children is highly prized as evidenced by the motives for parenthood among African couples such as carrying the family name, to provide assistance with household chores, to provide for and look after the elderly, as well as, to obey a religious command to reproduce, for joy and companionship, for respect and status in society. Therefore, infertility is not taken lightly in some cultures and may have negative implications on marital and sexual relationship, as well as on the psychological well-being and quality of life [5–7].

Although infertility can result from both the male and/or the female, often the female partner is the one that faces the most pressure since it is believed that the failure to conceive could be due to the inability to fulfill one’s role as a woman and this echoes the Chadian proverb that says: “A woman without children is like a tree without leaves.” [7, 8]. The implications of involuntary childlessness due to infertility in the African context to name but a few range from polygamous relationship and therefore risk of Human immunodeficiency virus (HIV) acquisition, divorce, domestic abuse or maltreatment, loss of social security, lack of domestic support in the home, poverty or high dependency among elderly people, lack of respect and status in society, social isolation and humiliation [5, 6, 9–11].

Although assisted reproductive technology (ART) has given hope to many families across the globe, little is done to give support to men, women, and families affected by infertility in Sub-Saharan Africa. Therefore, the purpose of this study was to determine the effectiveness of ART treatment on pregnancy outcomes and assess possible risk factors that lead to infertility in order to address the challenge of involuntary childlessness that is so common in developing countries such as Namibia where private and/or government funding/support initiatives are not available for patients.

Materials and methods

Research design

This was a prospective and descriptive cross-sectional case reference study encompassing infertile women visiting the Cape Windhoek Fertility Clinic. The study was both a qualitative and quantitative study by design.

Ethical considerations

Ethical clearance was sought and obtained from the Namibia University of Science and Technology (NUST) higher degree and the Ministry of Health and Social Services (MoHSS) ethics committees to carry out the study (Ref: 77 /3/3 AFL). Participation in the study was entirely voluntary with the option of participant’s withdrawing from the study at any point and time without consequences.

Population and setting of the study

The study population consisted of infertile women visiting the Cape Windhoek Fertility Clinic during the period from February to August 2019 and met the characteristics necessary to address the research question were included.

Size of sample

A total of 178 infertile women visiting the Cape Windhoek Fertility Clinic were selected using Cochran’s formula to formulate the sample population for this study, where: Z = 1.96, p = 0.35, e = 0.07. The population for this study was sampled using a purposive non-random sampling procedure to produce a sample that can be logically assumed to be representative of the population and subjective methods was used to decide which elements should be included in the sample based on the subject’s characteristics.

Sampling procedure

Venous blood samples were collected and analyzed for HIV, syphilis, HBsAg, HCV, TSH, AMH, and PRL levels before the commencement of treatment. The kits used were ARCHITECT HIV Ag/Ab combo, ARCHITECT Syphilis TP, ARCHITECT HBsAg Qualitative II, ARCHITECT Anti-HCV, ARCHITECT TSH, and ARCHITECT Total β-Hcg. After treatment, another blood sample was sent to the laboratory for analysis of serum hCG hormone level to determine biochemical pregnancy and whether or not the treatment was successful. All laboratory analysis was done using the Architect ci8200 and Cobas 6000 immunoassay analysers. The principles and protocols of the test were adopted from Abbott Laboratories, 2013, 2014a, 2014b&c 2015 2016b and 2017.

Data collection methods

A questionnaire was administered by the consulting gynecologist as part of taking patient history. The questionnaire served to gather first-hand information (i.e., age, last menstrual period (LMP), race, work industry, marital status, and lifestyle habits) from each participant.

Variables that were collected during pre- and post-treatment

This study entailed both qualitative and quantitative variables such as:

• Qualitative: work industry, race, marital status, lifestyle habits, and treatment option.

• Quantitative: age, number of children, and hormone levels.

Methods of data analysis

All raw data collected was initially sorted and grouped via the aid of Microsoft Excel software. To analyze our data we employed the analytics software, SPSS (Statistical Package for the Social Sciences version 25.0, SPSS Inc., Chicago, IL, USA) and the chi-square test was used. *p <0.05 was considered to be statistically significant.

Descriptive statistics (minimum, maximum, mean, and standard deviation) were applied for continuous variables and simple percentages for categorical variables.

Results

The study consisted of 178 patients classified as “infertile women” visiting the Cape Windhoek Fertility Clinic for ART treatment. Of these 178 women, 96 were infertile, while the remainder 82 were sub-fertile. The gravida-para status of these women determined whether they were classified as infertile (0 children) or sub-fertile (1 or more children).

The enrolled women in the study ranged from 25 to 50 years of age. The vast majority of the participants (n = 145; 81.5%) were married. The majority of women (n = 97; 54.5%) seeking infertility treatment were in the age group 30–39 years. Interestingly enough, this was also the age group that had the highest percentage of non-responders to infertility treatment (n = 67; 69.1%) as shown in Table 1.

Table 1.

Population demographics (n = 178)

Variables	Categories	Human chorionic gonadotropin categories
		Pregnancy negative		Pregnancy positive		Total		Chi-square (p value)
		Count	%	Count	%	Count	%
Age group (years)	20–29	5	55.6	4	44.4	9	5.1	0.077
	30–39	67	69.1	30	30.9	97	54.5
	40–49	47	68.1	22	31.9	69	38.8
	> 49	0	0.0	3	100.0	3	1.7
Marital status	Single	17	51.5	16	48.5	33	18.5	0.038
	Married	102	70.3	43	29.7	145	81.5
Race	Black women	98	68.1	46	31.9	144	80.9	0.646
	White women	6	54.5	5	45.5	11	6.2
	Mixed ancestry women	15	65.2	8	34.8	23	12.9
Work industry	Business/Finance/Admin	51	62.2	31	37.8	82	46.1	0.132
	Construction/Engineering	8	100.0	0	0.0	8	4.5
	Education	23	65.7	12	34.3	35	19.7
	Home-maker	12	85.7	2	14.3	14	7.9
	Law/Police/Military	17	70.8	7	29.2	24	13.5
	Medical/Health	8	57.1	6	42.9	14	7.9
	Unemployed	0	0.0	1	100.0	1	0.6
Gravida-para status	0	68	70.8	28	29.2	96	53.9	0.621
	1	12	60.0	8	40.0	20	11.2
	2	26	65.0	14	35.0	40	22.5
	> 2	13	59.1	9	40.9	22	12.4

From the 178 infertile women, 96 cases (53.9%) suffered from primary infertility and 82 (46.1%) women suffered from secondary infertility as shown in Table 2. Of those who presented with secondary infertility, most (40; 22.5%) already had 2 children.

Table 2.

Type of infertility and lifestyle habits

Variables	Categories	Human chorionic gonadotropin categories
		Pregnancy negative		Pregnancy positive		Total		Chi-square (p value)
		Count	%	Count	%	Count	%
Type of infertility	Primary infertility	68	70.8	28	29.2	96	53.9	0.222
	Secondary infertility	51	62.2	31	37.8	82	46.1
Smoking	No	118	66.7	59	33.3	177	99.4	0.480
	Yes	1	100.0	0	0.0	1	0.6
Alcohol drinking	No	95	66.4	48	33.6	143	80.3	0.810
	Yes	24	68.6	11	31.4	35	19.7

Most of the female participants were of Black African decent (144; 80.9%) and a large number of participants (82; representing 46.1%) indicated that they work in the Business/Finance/Admin sector.

In this study, the predominant cause of complications for infertility among the 178 women was defective ovulation 51 (28.7%) and the most common ART treatment administered was split In Vitro Fertilization/Intracytoplasmic Sperm Injection (IVF/ICSI) (93; 52.2%) (Table 3). In split IVF/ICSI, sibling oocytes are fertilized by two different methods using the same sperm sample in order to minimize fertilization failure and ascertain the probability of successful fertilization by IVF particularly in cases of unexplained infertility [12, 13]. ART cycles performed: 247, oocytes retrieved: 1353, oocytes fertilized: 1060, embryos implanted: 480, biochemical pregnancies achieved: 59, and embryos transferred (fresh: 424, thawed: 53).

Table 3.

ART treatment and treatment cycle

Variables	Categories	Human chorionic gonadotropin categories
		Pregnancy negative		Pregnancy positive		Total		Chi-square (p value)
		Count	%	Count	%	Count	%
ART treatment	FET	13	81.3	3	18.8	16	9.0	< 0.001
	IUI	2	28.6	5	71.4	7	3.9
	IVF/ED (donor eggs)	30	55.6	24	44.4	54	30.3
	IVF/ET (own eggs)	2	25.0	6	75.0	8	4.5
	IVF/ICSI (split)	72	77.4	21	22.6	93	52.2
Treatment cycle	1	89	68.5	41	31.5	130	73.0	0.315
	2	22	57.9	16	42.1	38	21.3
	> 2	8	80.0	2	20.0	10	5.6

Of the 178 patients 10.1% tested positive for HIV, 7.3% for HBsAg, 1.1% for syphilis, while all patients tested negative for HCV (Table 4). The majority indicated to be non-smokers (177; 99.4%) and did not consume alcohol (143; 80.3%).

Table 4.

HIV, HBsAg, HCV, and syphilis

Variables	Categories	Human chorionic gonadotropin categories
		Pregnancy negative		Pregnancy positive		Total		Chi-square (p value)
		Count	%	Count	%	Count	%
HIV	Negative	107	66.9	53	33.1	160	89.9	0.986
	Positive	12	66.7	6	33.3	18	10.1
HBsAg	Negative	114	69.1	51	30.9	165	92.7	0.024
	Positive	5	38.5	8	61.5	13	7.3
HCV	Negative	119	66.9	59	33.1	178	100.0	a
	Positive	0	0.0	0	0.0	0	0.0
Syphilis	Negative	118	67.0	58	33.0	176	98.9	0.611
	Positive	1	50.0	1	50.0	2	1.1

a: The chi-square test was not performed because there was no HCV  positive patients

Most of the women 130 (73.1%) received only one ART treatment cycle. Only 33.1% of the women undergoing ART treatment (59/178) eventually conceived, while the majority (66.9%; 119/178) did not respond favorably to treatment.

Discussion

ART remains inaccessible in many parts of the world, particularly in Sub-Saharan Africa, where IVF clinics are still not common or available in most countries [14]. Of the 178 women that received ART treatment at the Cape Windhoek Fertility Clinic, the majority 119 (66.9%) did not fall pregnant as compared to 59 (33.1%) that conceived. The pregnancy success rate from this study was comparable to the global success rate as reported in an editorial of Reproductive Biomedicine online [15], and this is owing to the ART treatment method employed in each case despite the fact that most participants only had 1 treatment cycle (Table 3) due to cost barriers.

Moreover, the findings of this study are relevant since fecundity rate has been on the decline in Namibia for the past 20 years as more women have become aware of the use of contraceptives and are seeking career advancement through further education, hence delaying marriage and childbearing altogether [16, 17]. Although infertility has been understudied in Namibia, the prevalence of infertility (66.9%) obtained from the participants in this study is alarmingly high and this confirms the widely known high prevalence of infertility in the developing world as indicated by other studies [2, 4, 18–20].

The data obtained in this study showed that the majority (94.9%) of women seeking ART treatment, with the hope of conceiving were > 30 years of age. Several studies [21–23] have well established that age plays a crucial role in one’s fertility status, particularly among women, and that with increasing age (> 35 years) so does pregnancy success rates decrease due to aging and decreased ovarian reserve [24]. This is evident from our results as 64% of the women that did not fall pregnant after ART treatment were > 30 years of age. Contrary to common knowledge about the relationship that exists between female age and fecundity rates [24, 25], it is worth noting that the highest (100%) successful pregnancy outcome after ART treatment was seen among women in the age group > 49 years, even though the study showed that there was no correlation between the age of the patient and the pregnancy outcome (chi-square; p value = 0.077). The high pregnancy success rates among this group (> 49 years) could be attributed to the effectiveness of the ART treatment administered to these women since our statistics showed that there was a correlation between the pregnancy outcome and the ART treatment (chi-square; p value = < 0.001) received and the fact that they all had 2 or more cycles of treatment. However, the younger women (20–29 years) had the second-highest (44.4%) pregnancy success rates instead. This could be attributed to a viable ovarian reserve given their age since female fertility has a “best-before date” of 35 years and age remains a paramount determinant in a female’s ability to conceive either naturally or by ART [24].

Of the risk factors assessed such as infections (e.g., HIV, HBsAg, HCV, and syphilis) and lifestyle habits (e.g., smoking and alcohol consumption) in this study, it was found that they contributed little to nothing in the predisposition of the women being infertile, since most women were STI negative and the majority did not smoke or drink alcohol as seen in Tables 4 and 2, respectively. This, however, is contrary to the findings of studies [5, 26, 27] previously conducted in developing countries that indicate the impact of STIs and lifestyle habits as contributing causative agents of infertility. Again, these variations could be due to each individual’s level of education and socio-economic status, whereby uneducated individuals coupled with low socio-economic background are more likely to participate in risky lifestyle behavior thus being exposed to STIs and smoking/drinking habits when compared to those who are educated and have a better financial standing.

Of the patients that tested positive, HBsAg positive women had the highest (61.5%) rate of successful pregnancy outcome compared to HIV (50.0%) and Syphilis (33.3%) positive women. Furthermore no correlation were found  between pregnancy outcome and HIV (p = 0.986) or Syphilis (p = 0.611) status. However, there was a correlation between pregnancy outcome and the HBsAg status (p = 0.024).

The relationship between HBsAg status and pregnancy outcome in women undergoing ART treatment remains a controversial subject [28]. Some studies [29, 30] have reported that HBsAg seropositive status of women tends to have negative implications on ART treatment outcomes and therefore reduced pregnancy outcome, while other studies [31, 32] found that there was no significant difference in pregnancy outcome between HBsAg seropositive and seronegative women. Po Mui Lam et al [33] showed that higher pregnancies and implantation rates were demonstrated among couples with wives being HBsAg seropositive but not among those with husbands being HBsAg seropositive. Because HBV can be found in cervical and vaginal secretion, the vertical transmission may occur from the HBsAg seropositive mother due to intrauterine exposure or transplacental transmission. Interestingly, HBV infection has been detected in newborns of HBsAg seronegative mother. Because HBsAg had been detected in semen and spermatozoa DNA [34, 35], proving father to fetus transmission and confirmed by direct sequencing [36].

African cultures place a high premium on children and therefore marriage is seen as an ideal platform for women to showcase their ability to reproduce, as evidenced by the fact that married women were the majority compared to single women in this study (Table 1). It is as though the marriage is not complete without children. Therefore failure to reproduce is often implicated by several consequences as evidenced by several studies conducted in Sub-Saharan Africa [5, 6, 9–11], in which women are often the victims of polygamous relationships and therefore risk of acquiring HIV, divorce, domestic abuse or maltreatment, loss of social security, lack of domestic support in the home, poverty or high dependency among elderly people, lack of respect and status in society, social isolation and humiliation. The outcome of this study showed that there was a correlation between the marital status and the pregnancy outcome (chi-square; p value = 0.038) and that single women had a higher (48.5%) successful pregnancy outcome as compared to married women (29.5%) (Table 1). This difference in pregnancy outcome between the married and single women could be attributed to the fact that single women choose to use donor sperm as part of their ART treatment, thus increasing their chance of a successful pregnancy outcome, while married women’s husbands might also suffer from male factor infertility, thereby leading to the lower pregnancy rates.

Moreover, the growing number of single women 33 (18.5%) seeking ART treatment could be because more single women are now willing to seek motherhood without the need of a male partner and it is becoming more socially acceptable or maybe due to same-sex relationships.

The study found that of the 178 women who underwent ART treatment, the majority 130 (73%) only received 1 treatment cycle, and this could be due to psychological, emotional and financial burden that comes with ART treatment and procedures, hence discontinuing seeking subsequent treatment cycles after failure to conceive on the first cycle [37]. Contrary to previous studies [38–40]  which confirmed that 2 or more treatment cycles result in higher pregnancy success rates, this study found that women who had undergone more than 2 ART treatment cycles had the lowest success rate (20%). Interestingly, women undergoing a single cycle of ART treatment had a 31.5% success rate, with those undergoing 2 treatment cycles having the highest success rate (42.1%). The contributing factor of high unsuccessful pregnancy rates among the women that had more than 2 treatment cycles could be the effectiveness of the ART treatment administered to these patients in response to the individual characteristics of these patients (i.e., age, coital frequency, type of infertility, lifestyle habits, and anovulatory disorders) as they may differ from woman to woman [25, 41].

For women to fall pregnant, they need to have functional ovaries, oviducts, and uterus. Therefore, any condition that affects any of these organs may lead to infertility. However, the problem of infertility may also be caused by male factor due to one or a combination of low sperm concentration, poor sperm motility, or abnormal morphology [42]. The data of this study showed that the predominant cause of complications that led to infertility among these women was defective ovulation (28.7%) and as per the Centers for Disease Control and Prevention (CDC), defective ovulation may be due to the following causes: endocrine disorders, physical disorders, ovarian disorders, and endometriosis [43]. These findings were similar to several other previous studies conducted [44, 45]. However, our findings differed from other studies [4, 5, 20] that attributed tubal factor as the most common cause of infertility due to STIs, infections and postpartum infections, particularly in Africa. Educated people could be less at risk of acquiring STIs as they are knowledgeable about the methods of transmission and its consequences, hence leading a more responsible lifestyle (e.g., do not part take in risky behavior or have multiple sex partners).

The AMH levels of the 178 women evaluated for ART treatment were grouped into 4 categories: negligible (11.2%), reduced (30.3%), normal (33.1%), and excessive (25.3%) response. AMH levels are useful in fertility assessment, as it provides guidance to ovarian reserve status and identifies women that may need to consider either egg freezing or trying for a pregnancy sooner rather than later if their long-term future fertility is poor. This study found that the highest rate of unsuccessful pregnancy outcome was among the patients that had a reduced ovarian response, followed by those with a negligible ovarian response, and excessive ovarian response as compared to those women who had a normal ovarian response (Table 5). These findings confirm what other studies [46, 47] have concluded, that AMH could be the most sensitive marker of ovarian reserve and therefore serve to guide both doctors and patients on the likelihood of pregnancy success depending on the ART treatment modality implemented. Although there is no correlation between the AMH levels and the pregnancy outcome (chi-square; p value = 0.173), one cannot overlook the usefulness of AMH in determining ovarian response when considering women for ART treatment.

Table 5.

Hormonal screening

Variables	Numeric values	Human chorionic gonadotropin categories
		Pregnancy negative		Pregnancy positive		Total		Chi-square (p value)
		Count	%	Count	%	Count	%
TSH	< 0.35 mIU/L	1	100.0	0	0.0	1	0.6	0.480
	0.35–4.94 mIU/L	118	66.7	59	33.3	177	99.4
PRL	< 5.18 ng/mL	6	66.7	3	33.3	9	5.1	0.913
	5.18–26.53 ng/mL	105	66.5	53	33.5	158	88.8
	> 26.53 ng/mL	8	72.7	3	27.3	11	6.2
AMH	< 0.15 ng/mL (negligible)	15	75.0	5	25.0	20	11.2	0.173
	0.15–1.14 ng/mL (reduced)	41	75.9	13	24.1	54	30.3
	1.15–2.56 ng/mL (normal)	34	57.6	25	42.4	59	33.1
	> 2.56 ng/mL (excessive)	29	64.4	16	35.6	45	25.3

Conclusion

The severity of infertility in the developing world is worrisome in comparison to the developed world. Involuntary childlessness continues to have serious social and economic impacts on the lives of those implicated, particularly women in the developing world. It is the silent cry of many African women and for some, it has reached as far as a sense of loss of one’s dignity and worth as a woman. Access to affordable ART treatment remains a challenge in low-resource settings (i.e., Africa) seen that for the most part they are only offered by privately owned hospitals and/or clinics at costly fees.

As suggested by Ombelet and Onofre [20], the successful implementation of low-cost infertility care in developing countries, particularly in public health facilities, would include the simplification of diagnostic and ART procedures, minimizing the complication rate of interventions, providing training-courses for healthcare workers and incorporating infertility treatment into sexual and reproductive healthcare programs.

Moreover, preventative measures to curb the challenge of involuntary childlessness such as dealing with underlying causes that may eventually lead to fertility, i.e., untreated infections, STIs, could also be adopted and implemented. Lastly, educating the public about infertility would alleviate the stigma faced by women in their communities and make man aware that they could eventually be the cause of infertility thereby not shifting the entire blame on their female partners.

Limitations of study

The outcome of this study may not give a clear indication of the prevalence of infertility among women in the entire Namibian nation due to the costs involved with ART treatment offered mainly at privately owned hospitals and/or clinics, thereby resulting in those who cannot afford treatment to be left out despite being infertile.

This study cannot conclusively determine the affordability of the entire Namibian women who may want to seek ART treatment since no data was collected on the average income earned by these women or the household, they are a part of. Besides, the data was not classified according to regions.

The cost of ART procedures may have limited most participants in this study to one treatment cycle and thus, we could not conclusively infer whether more than one treatment cycle would have increased the prospects of a successful pregnancy.

The risk factors (i.e., STIs) mostly attributed to the cause of infertility among women in developing countries could not be verified seeing that most women in the study were negative when screened for STIs.

Funding

This study was supported by Stellenbosch University.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict(s) of interest.