How Long Till Infertile Again After a Late Pill

• Journal List
• Contracept Reprod Med
• 5.3; 2018
• PMC6055351

Contracept Reprod Med. 2018; three: 9.

Return of fertility after discontinuation of contraception: a systematic review and meta-analysis

Tadele Girum

Department of Public Health, Higher of Medicine and Health Sciences, Wolkite Academy, Wolkite City, Federal democratic republic of ethiopia

Abebaw Wasie

Section of Public Wellness, Higher of Medicine and Wellness Sciences, Wolkite University, Wolkite Metropolis, Ethiopia

Received 2022 November 20; Accepted 2022 May 2.

Abstruse

Introduction

Along with increasing availability and utilization of contraception, It is also of import to confirm that the effects of contraception utilise on resumption of fertility afterwards discontinuation However currently evidences on resumption of fertility later on contraception employ are inconclusive and practically fertility after termination of contraception remains a big business concern for women who are using contraception. This fear poses a negative affect on utilization and continuation of contraception. Therefore, Estimating the charge per unit of pregnancy resumption after contraceptive use from the available reports and identifying the associating factors are important for designing a strategy to overcome the problem.

Methods

The review was conducted through a systematic literature search of articles published betwixt 1985 and 2017. Five bibliographic databases and libraries: PubMed/Medline, Global Health Database, Embase, the Cochrane Library, and African Index Medicus were used. After cleaning and sorting, analysis was performed using STATA version 11. The pooled rate of conception was estimated with a random-effects model. Heterogeneity was assessed by the I² and publication bias through funnel plot.

Results

Twenty two studies that enrolled a full of 14,884 women who discontinued contraception were retained for final analysis. The pooled rate of pregnancy was 83.1% (95% CI = 78.2-88%) within the start 12 months of contraceptive discontinuation. It was not significantly different for hormonal methods and IUD users. Similarly the blazon of progesterone in specific contraception choice and elapsing of oral-contraceptive use do not significantly influence the return of fertility following cessation of contraception. Yet the consequence of parity in the resumption of pregnancy following cessation of contraception was inconclusive.

Conclusion and recommendation

Contraceptive use regardless of its duration and blazon does not have a negative result on the ability of women to conceive following termination of use and it doesn't significantly delay fertility. Therefore, advisable counseling is important to clinch the women to apply the methods every bit to their interest.

Keywords: Return of fertility, Contraceptives, Intrauterine device, Implants, Pills

Background

Wide ranges of effective and safe reversible modern contraceptives are bachelor in the contemporary earth. Despite the advancement in contraceptive technologies and organized international effort over the final few decades; the concern of women who employ reversible contraception related to time to return of fertility still remained unanswered [one–iii]. Nearly contraceptives have been modified to improve their prophylactic and tolerability without compromising efficacy. Information technology is also of import to know the effect of contraception use on the subsequent fertility [1, 3].

However, currently evidences regarding resumption of pregnancy later contraceptive discontinuation are inconclusive. Delay of fertility subsequently termination of contraception remains a big concern for women who are using contraception. Specially women who ever experienced post pill amenorrhea or fail to become significant within expected date of fertility after termination of contraception have speculated contraceptive options crusade delayed return of fertility.

Decision-making unwanted fertility with highly constructive reversible contraception allowed couples to accept the number of children they desire at the time they want to accept. On the other hand fertility delay or damage as a result of prior contraception utilise may atomic number 82 to dissatisfaction and lower contraception use irrespective of actual desire [iii–7].

Approximately 15% of couples experience infertility (fail to get pregnant within ane year) [half dozen], women who use hormonal contraception take considerable concern of delayed or dumb fertility upon discontinuation. Delayed return of fertility or infertility amidst previous contraceptive users is ordinarily linked to their contraceptive use. Therefore, this premise that leads to misconception amongst family planning users need to be synthesized and tested using the bachelor evidences beyond the globe.

These concerns were also raised past scholars from early reports that Oral Contraceptive apply may cause secondary amenorrhea, which is associated with anovulation and reduced reproductive fecundity. IUD may also cause infertility secondary to pelvic inflammatory illness (PID) [7]. It was believed that exogenous hormonal therapy causes delayed return of normal function of hypothalamic/pituitary/ovarian axis [8–xi] and temporary infertility [12]. However these concerns were disproved from more recent studies partly from development of depression dose hormonal contraception, prevention of PID and implementation of scientific technique [xiii–sixteen].

There are a number of studies and few specific reviews conducted to appraise the effect of unlike forms of contraceptives on subsequent pregnancies. The findings were inconclusive, in some studies contraception shown to have only an initial (temporary) filibuster in conception for the first few months after discontinuation [13–16]. While in recent studies no clan was observed between contraceptive employ and secondary amenorrhea [17–nineteen] except with higher doses of oestrogen [20]. On the other paw many studies have reported that, the type of intrauterine device besides equally duration of use has not been found to exist related to fertility render [21].

Therefore, we aimed to conduct a comprehensive systematic review and meta-analysis through reviewing globally published observational studies on the effect of fertility return after discontinuation of different contraception amongst married and in union. Return of fertility is measured in terms of pooled rate of fertility return within i twelvemonth in order to bring conclusive evidence. So that policy makers and other stakeholder could have synthesized testify to rely on in decision making on prospect of the problem.

Methods and material

Literature search strategy

This systematic review and meta analyses is conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline [22]. Systematic literature search of articles was made. Articles published between 1985 and 2022 containing information on rate of pregnancy post-obit abeyance of reversible contraception were retained for systematic review and meta-analysis. Electronic bibliographic databases and libraries including PubMed/Medline, Global Health Database, Embase, the Cochrane Library, and African Index Medicus were used to call back published articles. Combination of search terms were used with (AND, OR, Not) Boolean (Search) Operators. (1: contraception discontinuation; ii: IUD discontinuation; iii: Implant discontinuation; 4: Hormonal contraception discontinuation; v: 1 or 2 or 3 or 4; 6: return to fertility; 7: rate of fertility; 8: time to pregnancy; 9: planned pregnancy; 10: fecundity; 11: filibuster in conception; 12: time to conception; xiii: pregnancy delay; xiv: time to ovulation, xv: 6 or seven or 8 or 9 or ten or eleven or 12 or 13 or 14; 16: five and 15). In improver the reference lists of principal and pertinent review articles were too uploaded into an EndNote Eleven library (EndNote, Carlsbad, CA, USA) to identify cited studies not captured past the electronic search and later all checked for duplications.

Study selection process and eligibility criteria

Studies published in English language anywhere in the globe that reported a 12 month pregnancy rates following discontinuation of a reversible contraceptive method with the intention to get pregnant, with sample size of 100 women and above, and prospective clinical/observational study designs were the inclusion criteria for this systematic review and meta-analysis. 1-year pregnancy rate was used to exclude women who developed secondary infertility. Unable to conceive despite of unprotected sexual intercourse with optimum frequency for one yr and to a higher place is called infertility, but the telescopic of this review is delayed return of fertility later cessation of contraceptive use. Therefore, 1 year rate of pregnancy is more informative to appraise delayed resumption to fertility than other time scales. The outcome of interest was the charge per unit of pregnancy among modern reversible ex-contraception users. However studies reporting rate of delivery as the only upshot, Studies published before 1985, studies assessing fertility after abortion or post ballgame contraception were excluded. Also Studies conducted in the aforementioned location during the same time period were considered as potential duplicates and therefore excluded from the analysis. 3 experts reviewed each article and decided based on the inclusion and exclusion criteria.

Information extraction and abstraction

Titles and abstracts derived through principal electronic search were thoroughly assessed for possibility of reporting pregnancy rates within 1 year period and filtered for potential eligibility. If needed, and whenever possible, the authors were contacted for clarifications. From each eligible research, the following information was extracted based on the preformed database (Excel, Microsoft, 2010) format: about author, study participants, studies (report design, sample size, study setting), Type of contraception, length of use, year of publication, year of study start and end, eligibility criteria, rate of pregnancy, etc. All data were extracted independently and in indistinguishable using a standardized extraction form. Returned abstracts were reviewed and total texts retrieved if they contained relevant information. At the aforementioned time, each selected research was assessed for methodological quality and possibility of bias. The effect variable (rate of pregnancy) was divers as the proportion of women who were pregnant inside i year of contraception discontinuation. The upshot size is measured in rates/proportion.

Cess of gamble of bias in individual studies and across studies

Adventure of bias in private studies and across studies was assessed through evaluating reliability and validity of data for each important outcome variables. Methods used to assess the outcome variable in each written report were also used to appraise hazard of bias. For all studies; the study blueprint, written report participants, the outcome, presence of loss to follow up were assessed based on the eligibility criteria and quality assessment check listing. Moreover all studies were prospective studies which employed the aforementioned participants and outcome was measured in the same standard. The chance of publication bias and heterogeneity was assessed through the standard statistical approaches. Nevertheless there are still uncontrolled biases at the selection of study participants, assay of the result and presentation/publication of the report.

Data analysis

After cleaning and sorting the final database was exported into STATA eleven.0 for analysis (STATA, College Station, TX, USA). An result of interest was rate of pregnancy later on discontinuation of contraception before or at 12th month. Estimate of pregnancy rate was assessed for each report and standardized mean with 95% confidence interval was used. These were calculated with a random effects model according to the DerSimonian and Laird method [23]. Heterogeneity was assessed by the I² and values greater than fifty% considered representing significant heterogeneity. When heterogeneity between studies was plant to be significant, pooled estimates were based on random-effect models and the Hedges method of pooling. Results were displayed visually in forest plots. Bias was investigated past structure of funnel plots and Analysis was performed using the 'metan' and related functions in STATA version 11 (College Station, TX).

Results

Studies included

From 114 studies initially identified, 22 [24–44] were retained for final assay based on the inclusion and exclusion criteria and quality assessment. From the initial search, literatures were identified as abstruse, bibliography and full text enquiry from the selected electronic data bases. Later on reviewing the abstracts, 62 possible researches were transferred to preformed format of endnote, searched for total text research and cleaned for duplications and 32 abstracts of articles were identified for full text review. Of these reviewed in full text, 30 were removed prior to analysis for unlike reasons: five studies overlapped with larger studies, iii studies were out of time purlieus and for 2 studies the pattern was ambidirectional (retrospective & prospective) cohort written report (Fig.one).

Flow nautical chart for written report search, choice and screening for the review

Description of findings

The studies enrolled a total of 14,884 women who discontinued contraception for the sake of pregnancy. Of them 735 discontinued implants, 139 discontinued injectable contraception, 2374 women discontinued IUD and 11,636 discontinued oral contraception. The primary consequence of the studies was rate of pregnancy after discontinuation of contraception at 12 calendar month. Some studies likewise assessed the possible reasons for delay in resumption of pregnancy. With duplicates, 5 studied implants [24–29], two injectables [xxx, 31], 5 oral contraception [32–36] and the rest 12 assessed return of fertility after discontinuation of IUD [37–43]. All included studies were prospective cohort and prospective observational designs conducted in dissimilar parts of the world and published between 1985 and 2022 with English language.

The mean exposure time (duration of use) of implant users extend from 29.1-55.8 months, injectable users have exposure fourth dimension of 21.three-35.7 months, while oral contraception users were exposed for 24-84 months and IUD users retained for 19-28 months. Survey characteristics are described in (Tablei).

Table ane

Characteristics of studies included in the review

Authors & FP method	Publication year	Type of contraception	Sample size	Duration of use	Pregnancy rate	Pattern of the study	Setting
Implants
[24] Affandi et al.	1999	Implanon	fourscore	hateful 35.iii month	48.lxxx	Prospective	Indonesia
[24] Affandi et al.	1999	Norplant	fourscore	mean 55.8 calendar month	37.fifty	Prospective	Republic of indonesia
[25] Buckshee et al.	1995	Norplant II	159	thirty.0 ± 11.five months	80.30	Prospective	India
[26] Sivin et al.	1992	Norplant 2	116	Mean 29.1 month	84.00	Prospective obs.	Not specified
[26] Sivin et al.	1992	Norplant VI	62	Mean 33.half dozen ± ane.nine	83.00	Prospective obs.	Not specified
[27] Singh et al	1989	Norplant	100		90.00	prospective	Singapore
[28] Affandi et al	1987	Norplant Half-dozen	51	32.4 ± 8.viii months	76.50	Prospective	Indonesia
[29] Diaz et al	1987	Norplant Six	87	1–8 years	85.half-dozen	Prospective	Chile
waited mean (12 month Render charge per unit of pregnancy among ex-users of implants)					74.70
Injectable
[30] Bahamondes et al.	1997	Cyclofem-monthly	70	seven.1 ± 4.6 cycle	82.ninety	Prospective	4 countriesa
[31] ICMR task Force	1986	Norethisterone	69	11.9 ± 4.9 months	72.50	Prospective	India
Waited mean (12 month Return rate of pregnancy amongst ex-users of injectable)					77.74
Oral contraceptives
[32] Barnhart et al.	2009	Oralcontraceptives	21		81.00	Prospective	multicenter
[33] Cronin et al.	2009	Oralcontraceptives	2064	7.ii yrs	79.40	Prospective obs.	7 countriesb
[34] Wiegratz et al.	2006	30 mcg EE/2 mgDNG	706	21.5 ± 16.8 wheel	94.00	Prospective obs.	Germany
[35] Farrow et al	2002	Oralcontraceptives	8497		88.00	Prospective	England
[36] Zimmermann	1999	31 mcg EE/2 mgDNG	348	med. four-6 cycle	95.00	Prospective obs.	Federal republic of germany
Waited mean (12 month Return rate of pregnancy amid OC ex-users)					87.04
Intra uterine device (IUD)
[37] Delbarge et al	2002	GyneFix	128	mean104.six ± 93wk	88.00	Prospective	Belgium
[38] Tadesse et al	1996	Copper T-200	780	med. three.5 years	86.00	Prospective obs.	Ethiopia
[39] Anderson et al	1992	Nova-T	71	Median 21 month	71.20	Prospective	five countriesc
[39] Andersson et al	1992	LNG-20 IUS	138	Median 19 months	79.10	Prospective	5 countries
[26] Sivin et al.	1992	TCu380Ag	103	mean 38.nine months	77.00	Prospective obs.	Non specified
[26] Sivin et al.	1992	LNG-20 IUS	91	mean 30.2 months	84.00	Prospective obs.	Not specified
[xl] Gupta et al.	1989	Copper plus Prog.	91	56% b2 years	92.thirty	prospective	Not specified
[28] Affandi et al	1987	Lippes C IUDs	75	31.8 ± 8.6 month	74.70	Prospective	Indonesia
[41] Skjeldestad et al	1987	Copper IUDs	101	56% b24 months	81.00	Prospective obs.	Norway
[42] Belhadji et al.	1986	TCu380Ag	50	23.96 months	91.10	Prospective	Non specified
[31] ICMR Chore Force	1986	Copper T-200	110	28.ii ± xiv.vii months	83.sixty	Prospective	Republic of india
[42] Belhadji et al.	1986	LNG-20 IUS	60	22.72 months	96.xl	Prospective	Not specified
[43] Randic et al	1985	all forms of IUD	576	59% b3 years	86.10	Prospective	Yugoslavia
Waited mean (12 month Return rate of pregnancy among IUD ex-users)					84.75

The 12 calendar month pregnancy charge per unit post-obit discontinuation of different forms of implant with the intension to have pregnancy was measured in eight studies (with duplicates). Based on this estimates, 74.7% of ex-implant users get pregnant within 12 months. Moreover a study reporting exceptionally lower rate of pregnancy (48.8% amid Implanon and 37.5% amidst Implant II-6) [24] is removed, the mean weighted pregnancy rate increases to 83.45%. With the same hormonal composition ex-injectable contraception users have a pregnancy rate of 77.74% which is estimated only with two studies and ex-oral contraception users have a pregnancy rate of 87.04.

I twelvemonth pregnancy rate following abeyance of unlike types of Intrauterine device (IUD) was 84.75%, which is weighted among 13 studies (with duplicates). The studies as well noted that there is no significant difference between unlike types of IUD in terms or fertility resumption. As well in this case pregnancy was resumed with in a cursory period of time following cessation of use or removal of the device.

The highest rate of pregnancy among implant users of xc% was reported by Singh et al. [27] in Singapore, while the highest resumption rate of 95% post-obit cessation of oral contraception was reported past Zimmermann et al. [36] among German language women and as high as 96.4% of ex-IUD users in Belhadji et al. [42] report were conceived within 1 yr. There is a wide overlap in the reported 1-year pregnancy rates afterwards discontinuation of dissimilar forms of contraception. The rate of pregnancy was unexpectedly higher amongst ex-oral contraception users, followed by IUD users. However this difference was not statistically pregnant.

Pooled estimates and tests

Heterogeneity tests showed significant variations between studies (Q = 611.5, P = 0.000), where Q-value, the weighed sum of squares on a standardized scale was significantly different compared with expected weighed sum of squares and I-squared showed that 95.3% of the observed dispersions are attributed to real rather than spurious variations. Also the funnel plot showed evidence of bias with some of the studies missing at the bottom rather than effectually the master effect. Accordingly, the Duval and Tweedie's trim and fill up test was practical to arrange for the publication bias.

The presence of heterogeneity and publication bias resulted in adjustment of the point estimate of the rate of pregnancy following cessation of different types of contraception nether a random upshot model from 84.36 to 83.1%. In a fixed effect model the pooled estimate of pregnancy charge per unit was 84.36% (95% CI = 83.3-85.iv%) and in a random effect model the pooled estimate of pregnancy rate became 83.i% (95% CI = 78.2-88%), while estimates of each study are unchanged. In all cases pooled guess from random effect model was used for study and give-and-take (Fig.two).

Forest plot showing the rate of one twelvemonth pregnancy following discontinuation of contraception, weighted according to random-effects model

The event of some demographic characteristics, like age at contraceptive discontinuation and parity on resumption of pregnancy were inconclusive from these findings. Some studies reported a decrease in resumption of pregnancy rates with increasing age [25, 26, 33, 37, 38, 41, 43] and others showing no such subtract with increased age [thirty, 34, twoscore, 42]. In addition, the effect of parity on pregnancy rates was inconsistent, with some studies suggesting that age-adjusted pregnancy rates were significantly college in multiparous women [33], while in another report it was lower among nulliparous women [41], unaffected by parity [26] and significantly lower among multiparous women in Delbarge et al. [37] report. The possible outcome of hormonal contraception and prolonged use of oral contraception on impaired fertility was not supported in these findings [25–31]. Higher level of fertility was observed amidst not-hormonal contraception users in many studies [37–43] nonetheless the departure was not statistically significant.

Discussion

Co-ordinate to this review 83.1% (95% CI = 78.2-88%) of women who discontinued contraception became meaning within the kickoff 12 months. Render of fertility at the offset year was not significantly unlike for hormonal methods and IUD users. Similarly type of progesterone in contraception and duration of oral-contraceptive use do not significantly influence return of fertility following cessation of contraception. Still effect of parity in resumption of pregnancy post-obit cessation of contraception was inconclusive.

The rate of fertility return in this review was comparable to other reports of reviews and articles which assessed specific types of contraception [45–48]. The rate of pregnancy for oral contraceptives, copper IUDs and the LNG-IUS ex-users was also overlap with each other and comparable to previous findings. Even so the finding was slightly lower than reports of women who discontinued barrier methods or using no contraceptive method of 85.2– 94% [49, l]. This difference may be due to the fact that hormonal contraceptives commonly take months to clear from the body which results in temporary delay in resumption of pregnancy for months [44, 47, 48].

One year pregnancy charge per unit of (37.5-90%) following abeyance of Implant also overlaps across different studies [45, 46]. In that location are studies which study uncommonly low charge per unit of pregnancy within 1 yr later cessation of contraception as evidenced past Affandi et al. [24] which reports (37.5 and 48.8% for Norplant and Implanon ex-users respectively). However when the report with low rate of pregnancy after cessation of contraception is removed the rate of fertility return is comparable to other methods. Moreover, no significant difference was reported between unlike forms of Implants. This may be explained by the fact that implants are impregnated with similar hormone which doesn't create a deviation.

Render of fertility following termination of IUD was not compromised at all and resumption ranges between (71-96%) with a mean of 84.75%. Moreover, type of IUD and duration of utilize as well every bit add-on of hormones to the device practice not compromise pregnancy [37–43]. In line with this finding Mansour et al. [45] reported pregnancy rate of 86.ane to 92.3% post-obit termination of IUD which is comparable to natural method users and not-users. This finding besides witnesses that prompt resumption of fertility after termination of IUD. Every bit explained by other findings type and duration of IUD utilise doesn't affair the rate of pregnancy later on abeyance [46, 47].

Information technology is commonly believed that oral contraception may compromise conception, however, this review reported higher rate of conception (87%). In line with this finding other researchers reported comparable render of fertility after abeyance of oral contraception [47–50] However, this review and meta-analysis appreciate presence of brief delay in render of fertility later on cessation of hormonal contraception use until the bioavailability of the hormone in claret is completely cleared. It is likewise noted that the 3 months hormonal contraception utilize hinders pregnancy, merely the effect is extremely low for12 month users and no effect for 24 calendar month users [32–36, 47–49]. The Concern of dumb fertility which was reported with loftier-dose of oral contraceptive pills in early on years is not a problem currently. This is due to presence of low dose contraception regimen for apply [33, 34, 48].

Our review also shows that the duration of contraception utilize was not significantly affected with return of fertility. It is in line to many studies included in the review [24–44] and the written report of some other researches [45–49]. On the other hand at that place are evidences which characterize women who used oral contraceptives for a longer duration may had a slightly lower rate of pregnancy than did women using oral contraceptives for a shorter menstruation of time [44] which could be the effect of historic period, in which fertility decreases as age advances.

However, since none of the studies were randomized control trials and most of the studies had pocket-size sample sizes, the possible relationship between extended utilise of hormonal contraception and the rate of resumption of pregnancy may not encounter through appropriate and reliable conclusion.

Similarly our review showed that the progestin type had no major effect on the rate of pregnancy over the short term and long-term. This is considering rather than duration, dose matters. Nonetheless currently only depression dose preparations are in use. Therefore, delay in fertility may not be mutual following termination of contraception use. In addition, return of fertility among women discontinuing extended or continuous OC regimens is similar to that observed with cyclic OCs [32–36]. This result was likewise reported from previous reviews assessing the return of fertility following cessation of oral contraception [45–fifty].

The upshot of parity on the rate of fertility was inconclusive. The finding of this review shows that parity may or may not raise fertility. Studies included in the review specially compared nulliparous and multiparous women which ignored the rate of infertility [44]. Therefore, college rate of pregnancy amongst multiparous women who are proved to be fertile are expected. In all cases baseline prevalence of infertility may influence fertility rates of women seeking pregnancy following discontinuation of a contraceptive method.

Conclusion and recommendation

Resumption of fertility following cessation of contraception was not affected by use of contraception, type of contraception, duration of utilize and type of progesterone. However the effect of parity in the resumption of pregnancy following cessation of contraception was inconclusive. Therefore, it is important to counsel women that prior contraceptive use regardless of its duration and type does not accept a negative event on subsequent fertility, so that they can cull and utilise the duration they want.

Acknowledgments

For all authors who provided usa information whenever we contacted them.

Availability of data and materials

Please contact authors or respective author.

Abbreviations

FP	Family planning
IUD	Intrauterine device
LARC	Long interim reversible contraception
MeSHs	Medical subject headings
PRISMA	Preferred reporting items for systematic reviews and meta-analyses

Authors' contributions

TG: Conceived the project, took the primary function in data conquering, assay, interpretation writing the manuscript, and publication of the project. AW: revised the project, involved in interpretation and manuscript training. Both authors revised the final draft of the manuscript.

Notes

Authors' information

TG: is Bsc/public health, MPH in Epidemiology and Biostatistics, Lecturer at Department of Public health, College of Medicine and Health Sciences, Wolkite Academy, Wolkite, Ethiopia.

AW: is Bsc/public health, MPH in Reproductive health, Lecturer at Department of Public health, Higher of Medicine and Wellness Sciences, Wolkite Academy, Wolkite, Ethiopia.

Ideals approval and consent to participate

Non applicative.

Competing interests

The authors declare that they have no competing interests.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Contributor Information

Tadele Girum, Phone: +251913652268, Email: moc.oohay@eledatmurig.

Abebaw Wasie, Phone: +251925090600, E-mail: moc.liamg@eisawabeba.

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055351/

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